Greetings from Maggie Bras Welcome to our 8th edition of the BRAS Drug Development Program’s newsletter. It has been twelve years since I lost my husband Robert to cancer, and I marvel at how the years move so quickly. During Robert’s battle with cancer, we grew frustrated with the lack of new drugs available to target his cancer. In our frustration, we asked the Princess Margaret Cancer Foundation what we could do to change this. Their answer was to create an endowment in drug development within Princess Margaret Cancer Centre, with Dr. Malcolm Moore at its helm. And so we did. Sadly Robert did lose his battle, but we did not lose our dream of helping others with cancer. Since his death on September 4, 2002, Robert’s dream has become a reality. The Bras Drug Development Program has become the largest program in Canada, and one of the top 5 in the world. We are dedicated to conducting early phase clinical trials involving patients with advanced cancer. Our program has had a global impact on cancer research, by providing personalized cancer care, giving the right treatment to the right patient at the right time. In this edition of our newsletter, we will meet two patients who have benefited from drug trials, but we are also going to learn how they are living their lives with cancer. We will learn how BRAS DDP trains the drug development physicians of the future; we will find out what genomics is; if we are winning the war on cancer; why immune therapy is showing promise, and be introduced to some of the physicians, and nurses who drive the BRAS Drug Development Program on a daily basis. Come with me, delve between these pages, and learn about the progress that has been made in cancer therapy in the last 12 years. Sincerely,
Maggie Bras President, Bras Drug Development Program Advisory Committee
“I AM NOT THE RESULT OF MY CIRCUMSTANCES. I AM THE RESULT OF MY DECISIONS.’” – ANONYMOUS
Greetings from the Mayor of Mississauga As Mayor of the City of Mississauga, I commend the BRAS Drug Development Program at the Princess Margaret Cancer Centre, and value greatly the important work being conducted, which is dedicated to the treatment, education and research of cancer. We all know someone who has been affected by cancer, and the BRAS Drug Development Program, under the directorship of Drs. Malcolm Moore, Amit Oza, Lillian Siu, Philippe Bedard, Albiruni Razak and Eric Chen, has achieved credibility on an international scale, and the advancements being made, will bring us that much closer to finding a cure for this dreaded disease, in the hopefully not too distant future. In addition to the innovative and ground breaking research being conducted, I commend the BRAS Drug Development Program for providing such outstanding support to those suffering with cancer. The community of dedicated and compassionate professionals behind this wonderful program, provides much needed hope to cancer patients, in order for them to live longer, healthier and more productive lives. Sincerely, Mayor Hazel McCallion, C.M. LL.D.
Greetings from Dr. Robert Bell It is a pleasure to see how the BRAS Drug Development Program has grown in personnel, stature, and impact, over the time since the Bras Family decided to make this transformational investment in patient care, at Princess Margaret Cancer Centre. Indeed, the Bras center has probably influenced the future of cancer care at Princess Margaret, as much or more than any other program that has been started in the past 10 years, and it is important to reflect on how this remarkable impact was created. The first element that has provided the framework for influence, relates to the vision of the founding philanthropists. Through their own experience, caring for husband and father – Robert Bras, the Bras Family understood the critical importance of studying the effectiveness of new drugs in the context of Ontario, and environment. The family understood that the presence of a drug development activity at Princess Margaret, would not only contribute to our understanding of what drugs are effective, in what cancer treatment situations, it would also allow our patients at Princess Margaret, and across Ontario, to get earlier access to potentially lifesaving or life extending pharmaceuticals. The increasing numbers of studies undertaken over the years, shows that the founders were accurate in their assessment of the importance of their gift. Secondly, it is important to have visionary, and capable leadership for a program. The selection of Dr. Malcolm Moore as the initial leader of the Bras Center, was crucial to its continuing success. Dr. Moore now leads by far the largest Department of Medical Oncology and Malignant Hematology in the country. The addition of Drs. Amit Oza and Lillian Siu to the team, enabled its international success. Both Dr. Oza and Dr. Siu, have now moved to take a leadership role in the Bras Drug Development Program, and also, they both play important leadership roles in the overall research program at Princess Margaret, as well as internationally. More recently, the addition of Drs. Philippe Bedard, Albiruni Razak, and other new recruits, has markedly broadened the reach of the program, so that virtually any cancer patient at Princess Margaret may get access to the program. The recognition of the Bras Program’s capacity, continues to be recognized through the very important arm’s length review of the programs productivity, which has resulted in continued funding from the National Institutes of Health (NIH), in the USA for the Phase 1 and Phase 11-111 elements of the Bras Program. This continued peer reviewed success, is particularly strong affirmation of the excellence of the people, and work that goes on in the Bras Drug Development Centre. Finally, it is important that a center recognizes the need for synergy, and capturing resources outside the program to support continued growth. The Bras Drug Development Program is at the forefront of the Princess Margaret Cancer Foundation’s Billion Dollar Campaign for Personalized Cancer Medicine. The Foundation has invested many millions of dollars a year, in support for genomic analysis, and sequencing of cancer mutations present in our patients’ cancers. Doctors at the Bras Program, can then analyze this genetic advice, to select potentially effective chemotherapy, based on the mutations evident in the patient’s cancer. This advanced form of personalized cancer medicine, combines the expertise, and funding in the Bras Program, with the expertise in the sequencing of cancers funded by the Foundation. It is a very powerful combination for innovative therapy, based on a careful cancer analysis. In summary, the BRAS Drug Development Program is an essential element of what makes Princess Margaret so special. The Bras Family was remarkably visionary in establishing this center, and Canadian cancer patients are certainly indebted to the family for their generosity. Robert S. Bell, MDCM,MSc,FACS,FRCSC President and Chief Executive Officer University Health Network
Greetings from Dr. Malcolm Moore The BRAS Drug Development Program at the Princess Margaret Cancer Centre is actively involved in developing better, long-lasting ways to treat patients with advanced cancers. We are now able to understand the genetics of cancer and this understanding is transforming our approaches to treatment. Cancer arises from changes that occur in the DNA of cells and these changes which can include mutations, duplications, and loss of DNA, lead to changes in how critical proteins are produced. These then drive a cell to become a cancer. We have learned that each patient has a unique set of genetic changes that causes their cancer, and to have a unique behaviour. That is why, two patients who have cancer that originated in the same part of the body, may respond quite differently to the same treatment. It’s all in the genes! Our mission at the BRAS Drug Development Program, is to find better cancer treatments and to match patients to therapies based on the genetic makeup of their specific cancer. It’s a personalized treatment plan tailored to each patient. 2013 was an exciting year in Cancer Drug Discovery. We are starting to see advances against some of the most difficult forms of cancer. Melanoma, traditionally one of the most resistant tumors to treatment can now be cured in some advanced cases from the use of immunotherapy; treatments that activate a person’s own immune system to fight their cancer. In other cases the use of ‘targeted’ agents matched to a genetic mutation that is seen in 60% of melanomas is demonstrating dramatic results. These treatments are now being provided at Princess Margaret, and at the Bras DDP Program we are now evaluating these approaches in many different types of cancers. At the core of our program is a detailed analysis of each patient’s cancer to define their critical genetic features, and then match them to the best treatment. We have been able to demonstrate a much better success rate when this is done. As our understanding of cancer grows, we are getting closer to a time when cancer is a word, not a sentence. Within the pages of this newsletter, you will have an opportunity to meet Bobbi and Lee, who are enrolled in drug trials within the BRAS Drug Development centre. You will learn about Princess Margaret’s breakthrough research in immune therapy and genomics; you will meet the cancer physicians of the future; learn about drug trials; hear from Mississauga’s Mayor Hazel McCallion, our Honorary Chair of the BRAS DDP; be greeted by Dr. Robert Bell the President and CEO of UHN; Paul Alofs, the Princess Margaret’s Cancer Foundations President and CEO; learn more on Innovation in Action at the BRAS DDP from Drs. Lillian Siu and Amit Oza, and the list goes on. Thank you to our donors, who have made the BRAS Drug Development Program a reality. Our success today and continued success, is because of you, along with the support of the Bras family, and the Princess Margaret Cancer Foundation. Sincerely,
Dr. Malcolm Moore Director, BRAS Drug Development Program Daniel E. Bergsagel Professor of Medical Oncology Head, Division of Medical Oncology and Hematology Princess Margaret Cancer Centre, UHN & Mt. Sinai Hospital
Bras Drug Development Program – Innovation in Action! The research into, and development of, novel anticancer drugs is an exciting and fast paced environment with new discoveries announced each and every day. Over the last year, the Bras Drug Development Program has been no exception, keeping busy with several high profile projects and exciting new announcements. The group’s efforts have continued to help pave the way for rapid access to new cancer drugs, increase our understanding of how cancer begins and continued to increase our understanding of the biology of cancer, and most importantly, how to stop cancer in its tracks.
1. New Clinical Trials
On average, the Princess Margaret Cancer Centre opens 100-120 new clinical trials of all types cancers each year. Last year alone, approximately 20 trials led by the Bras Drug Development Program were opened and made available to patients. This includes trials which afford patients access to new anticancer drugs and interrogate the biology of gynecologic cancers (ovarian, endometrial and cervix), breast and pancreatic cancers, and lymphoma. At any one time the group has upwards of 90 studies open at different phases of development and evaluation, with 300-400 patients being able to participate in novel anticancer treatment programs.
2. International Membership – Gynecologic Cancer Intergroup
The Princess Margaret Phase II Consortium (PMHC; PI: Dr. A. Oza) has been granted membership to the prestigious Gynecologic Cancer Intergroup (GCIG). This global group includes 27 other large cooperative trials groups investigating new drugs in phase III trials. Dr. Amit Oza Chairs the Phase II Working Group, responsible for designing and developing innovative early phase trials that require a global community approach. In fact, since membership last year, there are three new early phase trials that the team will work towards opening in centres across the world including: Australia, France, Japan, the United Kingdom, and the United States.
3. Influencing New Drug Development Decisions in North America:
Advancing new anticancer drugs requires a lot of research and strategic decision making to ensure the best and most promising agents make it to clinical evaluation. This year, Drs. Lillian Siu and Amit Oza Co-Chair the Investigational Drug Steering Committee (IDSC) at the US National Cancer Institute’s Cancer Therapeutics Evaluation Program. In this role, Drs. Siu and Oza lead the group of clinicians and researchers tasked with reviewing available drugs in development that should proceed to clinical trials. Working with the National Cancer Institute and Institutional Program Directors, they are directly responsible for ensuring the portfolio of new drugs have solid lab studies conducted, cover strategic areas of cancer research (signaling pathways, mutations etc.) and to steer the group that reviews strategic priorities.
4. Funding for Promising Bench to Bedside Research Ideas
Part of the drug development process includes conducting laboratory based studies to better understand cancer biology and how drugs may be affecting this. To this end, Dr. Amit Oza successfully received funding from the United States Department of Defense under the Ovarian Cancer Research Program - Synergistic Translational Leverage Award opportunity. Alongside Co-Principal Investigator Dr. Gang Zheng, the group is aiming to develop a new nano or microscopic particle that can target specifically to ovarian tumours. Known as a porphysome, preliminary studies from Dr. Zheng’s group have shown that these particles which cannot be detected by the human eye, successfully hone in to ovarian tumours. The group has equipped them with properties that allow them to become visualized by imaging technology currently in use (Positron Emission Tomography – PET). Ultimately, this project will provide healthcare teams with visual confirmation that all of a patients tumour has been removed after surgery as well as to detect where the cancer cells may have spread to. The group also received funding from the Ontario Cancer Institute, to better understand the biological differences that exist in women who have ovarian cancer, for 10 or more, from those women who suffer from the disease for a shorter period of time (such as 2 – 5 years). The project team includes world leading immunology experts Dr. Pamela Ohashi and Dr. Marcus Butler, and molecular pathology expert Dr. Patricia Shaw.
Dr. Lillian Siu and Dr. Amit Oza Co-Directors of the Bras Drug Development Program Co-chairs of the Investigational Drug Steering Committee (IDSC)
Greeting From the Chairs Believe in Fashion was a dream, which grew into a reality in 2012. Our show took root with the incredible support of The Room of the Hudson’s Bay – our presenting sponsor. Our 2012 show featured the fashions of New York designer, Narciso Rodriguez, who over the past two decades has redefined American style. Believe in Fashion supports the BRAS Drug Development Program at the Princess Margaret Cancer Centre, the most important program in Canada for the development of cancer drugs, and one of the top 5 worldwide. Jeanne Beker, Toronto’s very own influential woman in the fashion industry, was our afternoon’s M.C.; Robert Kidd, a patient going through drug trials at the Princess Margaret, gave a moving speech on his journey with cancer; Dr. Malcolm Moore, Director of the Bras Drug Development Program, and Head of the Medical Oncology & Haematology Department at Princess Margaret, gave a few words about the program’s drug trials and spoke about Robert Kidd’s treatment; Maggie Bras talked about her husband’s cancer experience, and about the importance of drug trials. Randy Bachmann sang two of his famous songs, and shared one very moving song about cancer, and pianist Kenny Munshaw entertained our guests upon arrival. Paul Alofs, the President and CEO, of Princess Margaret Cancer Foundation, said a few words, and found himself walking through the models dressing room while making his way to the podium! We heard from Bonnie Brooks, the President of the Hudson’s Bay; were treated to a delicious lunch prepared by O & B; had a very special guest present – Canada’s own first lady, Mrs. Laureen Harper, and finally were treated to Narciso’s 2013 spring/resort fashion show. But most of all, we had a roomful of beautiful women, and a handful of handsome men, who thoroughly enjoyed themselves, while raising $135,439 for the Bras Drug Development Program! With this kind of support, and with this year’s sold out show featuring Erdem, from London, England, we will conquer cancer in our lifetime! Chairs, Maggie Bras, Holly Miklas and Tracey Neziol
Photos courtesy Korby Banner “A CANDLE LOSES NOTHING BY LIGHTING ANOTHER CANDLE.” – ERIN MAJORS
ABOVE: BRAS DDP DOCTORS MALCOLM MOORE MD DIRECTOR, BRAS DRUG DEVELOPMENT PROGRAM DANIEL E. BERGSAGEL, PROFESSOR OF MEDICAL ONCOLOGY, HEAD, DIVISION OF MEDICAL ONCOLOGY & HAEMATOLOGY PRINCESS MARGARET CANCER CENTRE, UNIVERSITY OF TORONTO LILLIAN SIU MD CO-DIRECTOR, BRAS DRUG DEVELOPMENT PROGRAM PROFESSOR OF MEDICINE DIRECTOR OF PHASE 1 PROGRAM AND CLINICAL GENOMICS PROGRAM. PRINCESS MARGARET CANCER CENTRE, UNIVERSITY OF TORONTO ALBIRUNI RAZAK MD ASSISTANT PROFESSOR OF MEDICINE, STAFF MEDICAL ONCOLOGIST, BRAS DRUG DEVELOPMENT PROGRAM PRINCESS MARGARET CANCER CENTRE, UNIVERSITY OF TORONTO AMIT OZA MD CO-DIRECTOR, BRAS DRUG DEVELOPMENT PROGRAM PROFESSOR OF MEDICINE DIRECTOR OF CANCER CLINICAL RESEARCH PRINCESS MARGARET CANCER CENTRE, UNIVERSITY OF TORONTO ERIC CHEN MD ASSOCIATE PROFESSOR OF MEDICINE DIRECTOR OF PHARMACOLOGY LAB, BRAS DRUG DEVELOPMENT PROGRAM PRINCESS MARGARET CANCER CENTRE, UNIVERSITY OF TORONTO PHILIPPE BEDARD MD ASSISTANT PROFESSOR OF MEDICINE, FELLOWSHIP DIRECTOR, BRAS DRUG DEVELOPMENT PROGRAM STAFF MEDICAL ONCOLOGIST PRINCESS MARGARET CANCER CENTRE, UNIVERSITY OF TORONTO RIGHT: BRAS DDP TEAM
Physician Leaders in Drug Development of the Future It’s my pleasure to introduce you to 4 Fellows who are currently training with the Bras Drug Development Program. We’ll explore their current role in the program, and where they hope and expect to go from here. I’ve also included a map of the world to give you a sense of how truly international our program has become, by pinpointing countries of origin of each current and past fellow. The Fellowship Program is a community. Relationships that start there, continue well after their fellowship training at Princess Margaret. Current, and former BRAS DDP fellows, meet every year for a luncheon at the American Society of Clinical Oncology Annual Meeting. They catch up on their friendships; their current positions, and what corner of the world they are working in. The bonds formed during the BRAS DDP fellowship training, produce lasting worldwide collaborations related to early phase clinical trials, research methodology, career support, and mentorship. Join me in welcoming in this edition of the Bras Drug Development Program newsletter, our current and past Fellows – the Physician Leaders in Drug development of the future!
There are now 8 BRAS DDP fellows from eight countries around the world. Our current fellows have authored or co-authored twenty abstracts, and thirteen manuscripts from work relating to their fellowship training. They also have received fourteen awards from national or international societies, and granting agencies. There are twenty-seven former fellows from ten countries, who currently work in eight countries including Canada. Our former fellows authored or co-authored a total of 174 abstracts, and 231 publications, arising from work related to their BRAS DDP training. They received a total of 59 awards during their fellowships. 85% of our former fellows currently hold university appointments at the level of Assistant Professor or higher. 69% are involved in clinical research in academia or industry, in the area of early drug development. We are proud that many former fellows hold leadership positions in academic phase 1 clinical trials units. With this worldwide community of present, and former fellows collaborating in the area of early drug development, we have reason to believe that We Will Conquer Cancer in Our Lifetime! Maggie Bras
Physician Leaders in Drug Development of the Future – Current Irene Brana – Spain David Cescon - Canada Joanne Chiu – Hong Kong Wei-Wu Chen – Taiwan Natalie Cook – UK Donna Graham – Ireland Aaron Hansen – Australia Anna Spreafico – Italy
Former BDDP Fellows Mark Agulnik – Montreal, Canada (now in Chicago, IL) Vincent Castonguay – Quebec City, Canada Nichole Chau – Toronto, Canada (now in Boston, MA) Neesha Dhani – Toronto, Canada Ivan Diaz-Padilla – Madrid, Spain (now in Basel, Switzerland) Ignacio Duran – Madrid, Spain (now in Seville, Spain) Christine Elser – Germany (now in Toronto) Hui Gan – Melbourne, Austraila, (now in Melbourne) Christophe Le Tourneau – Paris, France (now in Paris) Linda Lee – Edmonton, Canada (now in St. Catherines) Herbert Loong – Hong Kong (now in Hong Kong) Bridgette Ma – Hong Kong (now in Hong Kong) Arif Manji – Toronto, Canada (now in Newmarket, ON) Alberto Ocana – Albacete, Spain (now in Albacete, Spain) Albiruni Razak – Malaysia (now in Toronto,ON) Daniel Renouf – Edmonton, Canada (now in Vancouver, B.C.) Solmaz Sahebjam – Iran (now in Tampa, FL) Srikala Sridhar – Canada (now in Toronto) Anastasios Stathis – Greece (now in Bellizona, Switzerland) David Tan – Singapore (now in Singapore) Patricia Tang – Canada (now in Calgary, Alberta) Sara Taylor – Canada (now in Kelowna, BC) Carol Townsley – Canada (now in Toronto) Ben Tran – Melbourne, Australia (now in Melbourne, Australia) Laura Vidal – Spain (now in Barcelona, Spain) Steven Welch – London, Ontario Canada (now in London, ON) Benoit You – Lyon, France (now in Lyon, France)
Dr. Anna Spreafico,Clinical Research Fellow – Milan, Italy Anna was born in the Lake Como region of Italy, and at 18 she moved to Milan. It was there that she obtained her medical degree, and completed her medical oncology training. She then moved to Denver, Colorado to pursue her PhD in drug development and *translational research. Anna then applied to the Princess Margaret Cancer Centre in Toronto, for a fellowship position, at the BRAS Drug Development Program. When we sat down in October of 2013, it was the beginning of Anna’s second year.
Why The Princess Margaret?
“Princess Margaret is one of the most internationally recognized cancer centres in the world, with a solid drug development program, led by *Dr. Siu, who I had the opportunity to meet before I came here. Her work and her dedication have been so inspiring.”
Why did you take up medicine?
“I love science. I am not necessarily interested in a perfect science, and medicine is very well balanced between science, and human feelings, and relationships with people. This has motivated me to pursue this career.”
“That is a tough question. Science and molecular biology, have always been my interest. When I started medical school, I realized there was still a lot to be learned regarding the biology of cancer. In addition, I also experienced the reality of cancer in my family, and the combination of both led me to this field.” Is it unusual to have a clinical setting and a research setting under one roof? “In my country, it is very difficult to work properly in the clinic and pursue research. Despite the hard work, and dedication, unfortunately the economic situation, and the lack of resources, limit the ability to be productive in the research setting. That is why, even if you work hard, sometimes you cannot accomplish what you can do here. This institution provides invaluable opportunities to merge clinical and research activities.”
You heard about The Princess Margaret in Italy?
“Definitely. In the Medical Oncology field, Princess Margaret is known as one of the top Cancer Centres. It is very well recognized international.”
What is your role as a Fellow at the BRAS Drug Development Program?
“I came here mainly to concentrate in drug development and most of my time has been dedicated to this area, both in terms of seeing new patients in the clinic, as well as following them throughout their daily/ weekly treatment. Clinically, I have the opportunity to work in the melanoma field, where there is a lot of exciting research, given that several new drugs not available a few years ago, are now routinely used. In addition, I am also gaining experience in the GI field, following this clinic once a week. Most recently, I’ve been working with Dr. Siu in the Head and Neck clinic. Aside from the clinical experience, this fellowship provides the opportunity to be productive in the research setting. Our mentors make sure all of the Fellows have one, two or even more projects to develop, follow and complete, during our time at the Bras Drug Development Program at Princess Margaret. The research projects may vary based on the fellow’s interest. As for me, I love pre-clinical research, and everything that is related to molecular biology. As a part of the molecular profiling team, I had the opportunity to develop a research protocol, aimed to perform a deep sequencing analysis of the tumour tissues of patients. The main endpoint of all these studies, is to better understand the molecular characteristics of each patient tumour, and hopefully provide the most appropriate and personalized treatment.”
Who are your mentors at the BRAS Drug Development Program?
Although in the BRAS DDP I have been working with all staff – Drs. Siu, Bedard and Razak, my mentor is Dr. Lillian Siu.
What do you think are some of the major advances we have had the last few years in cancer research? “There is lots of them! Melanoma is the perfect example to prove that translational research has changed dramatically in the treatment, and management of patients affected by this disease. A few years ago, patients with advanced melanoma, had very limited treatment options, with unfortunately very frustrating unequivocal decisions, that involved either chemotherapy or symptoms management only. Nowadays, given the availability of several new therapies, and clinical trial options, medical oncologists are faced with treatment decisions that have become more and more difficult. They require deeper analysis, and
extensive multidisciplinary discussions. The availability of several treatment options is sometimes quite overwhelming for patients, who ask physicians what it the best choice, the best therapy? There is not always a straightforward answer.”
“A lot of patients ask us this question – if cancer can be cured. I say to patients, that although sometimes it is not possible to eradicate the cancer, I do believe that ‘cure’ could be achievable, to live a good quality of life, despite the disease. If we can do this, then we have accomplished a lot.”
What inspires you?
“What inspires me is what has been accomplished so far. All these amazing cancer discoveries, as well as the need we still have for all the patients out there. That’s the motivation. Human beings can be inspiring, and science can as well. The combination of both, is so exciting and fascinating, that’s it is difficult not to pursue this road.”
You have enthusiasm and a passion for your job.
“There are a lot of Fellows here at Princess Margaret. Most of them come from difference places of the world. If this is not driven by passion, then it’s hard to know what else it can be. It takes a lot of effort to leave your country; your family, your comfort zone, and sometimes your good life, and adjust to a completely different environment. I definitely believe all of us have a great passion for what we do.”
Are you going back to italy after your two years are up?
“I am not sure if I am going back to Italy. Of course my family is there, so it is tempting. But I know my family is happy if I am happy with the work, and the place I live in. I am looking for a position, which doesn’t necessarily have to be at home. I think it has to be where I’ll be happy and comfortable. I am happy and comfortable here as well. So we will see.”
How do you like Toronto?
“Toronto is great! I am in love with big cities, and Toronto offers lots of things to do. It has a dynamic environment. Milan is so much like that. There is a little bit of Europe here that I’ve missed for so many years, while I was in the United States.”
What makes the Princess Margaret Cancer Centre and the BRAS Drug Development Program one of the top five in the world?
“Top places are made by great people who are really dedicated. I don’t think this can be only a career, rather something you truly believe in. So it is your passion, correct? There is a lot of motivation and inspiration here, and throughout the years, the Princess Margaret and the Bras Drug Development Program have gained international recognition, which has made it a great place to learn and grow.” Thank you Anna. Maggie Bras • Translational research, is scientific research, which focuses on areas that can be translated into the clinic, which can have practical/helpful application. In our case, this can be meaningful for the patients. • Dr. Lillian Siu, is the Director of the Phase 1 Clinical Trials Program, and a Co-Director of the BRAS Drug Development Program.
Dr. Herbert Loong, Clinical Fellow – Hong Kong What is a Fellow?
“A Fellow is typically a doctor, from Canada or abroad, who has completed specialist training in Medical Oncology. All of the Fellows in the BRAS Drug Development Program (BRAS DDP), are already recognized specialists in Canada or their home country. Aside from taking care of oncology patients on a day-to-day basis, a large proportion of Fellows also have had prior experience in clinical trials and research in their home institution. This particular fellowship to the BRAS DDP, is a 1 to 2 year fellowship for most of our Fellows. By being part of a team, we gain exposure and practical experience, on how early phase clinical trials are conducted. Each of us also has academic projects that run longitudinally throughout our 1- to- 2 year stint at the Princess Margaret Cancer Centre. Supervised by the staff physicians, Fellows are heavily involved in the daily management of patients. In terms of day-to-day contact, it’s really the Fellows as well as the nurses who run the program.”
Why did you become a medical doctor?
“That is a very good question. The last time I was asked this was in my interview for medical school more than 15 years ago! It has to do with some personal experiences, and exposure as a teenager, as well as what medicine really meant to me. I’ve always been interested in science during my secondary school years and my A-Levels. It was all very science based. Yet I was also very involved in the humanities as well, within the school. I thought being a doctor was a good balance between science and humanity. Certainly day-to-day patient contact is very humanitarian, and require certain proficiencies in inter-personal and communication skills. Yet the science behind medicine and health forms the basis of these contacts as well. On a more personal note, around the time when I was looking for a University placement, my grandmother got sick and was hospitalized, and subsequently died of a stroke. I spent a fair bit of time in the hospital with her during her final days, and realized that medicine is very much a team effort. Patients got better, not only because of the doctor, but everyone in the healthcare team played an essential role. I wanted to be a part of that.”
Why did you chose oncology?
“I think it’s the expansion of the same theme. The balance between science and humanity. I think this is an exciting time for cancer medicine, and the science behind it is fascinating. On completion of my internship, I was deciding between Surgery and Oncology. Whilst both specialities treat patients with cancer, they are also on extreme ends of a spectrum. Surgery is certainly exciting with a lot of science for sure. Many a times, there is a very early sense of accomplishment as well when things are ‘fixed’ after an operation. However, you do not get the human touch per se. When you see a patient on the operating table, you may see them after the operation for one or two more visits, but that’s pretty much it. There is not much continuity in follow-up. On the other hand, as an Oncologist, patients are under your care throughout their entire cancer treatment journey – during both good and bad times. Due to obvious historical reasons, we in Hong Kong operate a healthcare system based on how things are done in Britain. Our trainings are accredited by the Royal Colleges in the United Kingdom. Typically, our oncologists are Clinical Oncologists and are trained to give radiation therapy as well as chemotherapy. However, given the complexity and recent advancements in cancer drugs and treatment, Medical Oncologists are playing a much more pivotal role in cancer care. We are internists who specializes in not only the provision of chemotherapy and systemic treatment, but are often involved in clinical and translational research. We are a relatively young specialty in Hong Kong. I am actually ‘Medical Oncologist No. 27’ on the Hong Kong Medical Council Register. We have a population of 7.5 Million! You can see how small this niche is. All of the fellows at BRAS DDP are Medical Oncologists who are further specializing in Developmental Therapeutics – i.e. the testing and research of new drugs and targeted agents.”
Why is it a good time to be in the cancer field?
“I think it is a good time to be in the cancer field, because we are now finding out more about ‘why’ and ‘how’ cancer develops. We are at a point when we now have the technology to analyze a particular patient’s tumour and to choose the most appropriate drug for them. This would not have been imaginable 10 years ago. I think in the last 5 to 10 years, this technology has really expanded. The costs have come down, and we are making real differences in terms of patient care. For example: As part of IMPACT (Integrated Molecular Profiling in Advanced Cancers Trial) at the Princess Margaret Cancer Centre, we are able to select patients with particular genetic mutations, and match them to specific trials, investigating targeted drugs that act on those specific mutations. We are able to see a lot more responses to treatment, and certainly a lot more patients are able to benefit. This has been a real ‘eye-opener’, and we are in the process of setting up a similar program in Hong Kong.”
Is this what we are calling Personalized Cancer Medicine?
“Yes precisely. And I think this is only the first wave. I am certain there is more coming. As the technology becomes more mature, and more popular, and as we know more about different molecular targets, hopefully this drive will continue.” “ATTITUE, GRATITUDE, AND HOPE.” – LEE PETTERSEN
What has inspired you since you’ve been here?
“I think the most inspirational aspect is the team work that goes on at the BRAS DDP. The fact that there are so many roles that people play, and there are so many people within it. The unit works like clockwork. On the surface, we may appear to be a small team of doctors and nurses, but in actual fact, there is a large group of healthcare professionals including research coordinators, statisticians and administrators, who keep this machine well-oiled and the momentum going. This in itself is quite amazing, and most certainly important. This is the only way this unit would ever function, because of the sheer number of clinical trials we conduct, and the number of patients we see. I think that has been the most inspirational. Patients themselves are also very inspirational - and their families. The patients here are to a certain degree, similar to the ones that we see in Hong Kong. Yet they are very different. Similar in the sense that everybody is going through a tough time with cancer, yet different. I feel the patients here are more in tune with the whole theme of Personalized Cancer Medicine. Being on a clinical trial has its benefits to the patients, as well as to the science. They are more willing to be a participant in the trial. Back home this is certainly the trend, but it’s still quite difficult. Maybe it is because as a predominantly Chinese society, we are more conservative. Hopefully this will change. There are opportunities here, and it’s been good. It is out in the public now, that the only way cancer treatment can move forward, is by improving our knowledge, and the only to do that, is having clinical trials, and by being a participant is a good option!”
Why are you here?
“The reason why I am here is, similar to the BRAS DDP, my hospital in Hong Kong has also newly established a Phase 1 Clinical Trials Unit. We shall be performing earlier phase drug testing and clinical trials for cancer patients. The BRAS DDP is a renowned unit in this field, and has a very high position globally. I am quite sure this is the most successful unit in Canada! More importantly, whilst the Princess Margaret Cancer Centre is by no means the biggest cancer centre in North American, nor does it have the most number of patients, this cancer centre and specifically the BRAS DDP, provides a good balance between patient volume and teaching. It is an absolutely great program.”
What are some of the advantages of being a BRAS DDP Fellow?
“One of the biggest advantages of being a BRAS DDP Fellow, is to be able to meet other Fellows. Right now, we have 7 Fellows from all corners of the world: Spain, Italy, Australia, the UK, Ireland, Hong Kong and also Taiwan. There is very good camaraderie. We work with and bounce ideas off each other. There is also a growing BRASS DDP alumni consisting of ‘graduated’ Fellows! Most of them are now established academic oncologists in various premier cancer centres around the world. In 10 to 20 years’ time, these Fellows will be the “movers and shakers” of Oncology. It is important to build up this network. This is an advantage for me to bring home.”
What are the phases? How many are there?
“In the drug development, in the clinical development, when the drug is actually being exposed to humans, we divide the phases into four different phases: Phase I is the first phase when the drug has been tested in the laboratory, as well as in animals. We then bring it forward to human testing. So most of the time, these are First-In-Human testing where no human patients having been exposed to these drugs before. The main reason why we do these phase 1 trials, is to assess the side effects of these drugs. Although we have tested them in animals, it doesn’t necessarily mean that it will be translated to humans. The other reason why we do it, is we need to ascertain what the correct dose is in terms of humans. We recruit patients into a trial, and we test the drugs at different doses. We monitor them very closely to make sure there are no particular side effects, and at the end of the trial, we establish what we call a Recommended Phase 2 Dose for subsequent testing. The next phase of testing would be a Phase 2 trial where the drug, having gone through phase 1, we have established the recommended dose. The main reason we do this trial is to see whether or not there is any clinical efficacy. The next phase would be a Phase 3 trial, where we compare it with what we have as standard treatment for that particular cancer. That’s the big trial where it requires numbers in the hundreds, and to compare with our standard treatment, to see whether this new drug is any better than what we currently have. Typically, if the phase 3 trial shows an advantage of the new drug over the current treatment. The drug then obtains approval from various health authorities around the World and is entered into the market. A Phase 4 trial, is a ‘look back’ trial where you look at the data of typically over 1000 patients who have been on the drug, and say: Hey is this drug really working, or has the data before been not very accurate? Are there particular safety or other concerns about this drug that may not have been picked up during the earlier phases of testing, where there were only a small number of patients? The numbers of patients also grow as you go up in terms of phase. For example: In phase 1 trials, we are dealing with a very small number of patients, but we watch them very carefully. The nature of phase 1 trials, means that they are typically con-
ducted in higher specialized centres with a proven track record, and experience in the field. Trials are typically conducted globally across multiple cancer centres. That is essentially drug development in a nutshell!”
How long does this process take starting at phase 1 and ending at phase 3?
“The time frame we are talking about is 8 to 10 years, for any drug to go through, from laboratory, to phase 1, all the way through to approval, and then to market. Certainly the average time from laboratory to actual approval can vary. Only less than 10% of cancer drugs that are tested in a phase 1 trial, ever becomes registered as a phase 3. Why? Because drugs that may have shown promise in the laboratory, or in animals, may not necessarily perform well in the humans.”
What are the advantages of being a participant in a phase 1 trial?
“The advantage of being in a phase 1 trial, is you’re able to receive drugs that would not otherwise be on the market! But there are also uncertainties, given the fact that we are looking at side effects. We are not in full understanding of the side effects of the drugs. Having said that, phase 1 trials are conducted in a manner where patient safety is of paramount importance, and the clinical trials are designed, together with the physicians involved, always err towards the side of caution. Some may argue that being a patient in a phase 1 trial is even safer than a patient on standard treatment, as our patients are monitored very closely, with very frequent (often at least weekly) visits and check-ups.”
Are we making progress in the war on cancer?
“I think so. I think we are certainly heading in the right direction. We have made some significant steps, but there is still a long way to go. There is still a lot of uncertainties, but we certainly are heading in the right direction.”
There is a big banner outside this hospital: “We Will Conquer Cancer in our Lifetime.” In your lifetime, do you believe this will happen?
“I hope so. I believe we are generally better in terms of health care. Not just cancer as a whole, but our life expectancies are also increasing as well. I think we have certainly solved one of the main hurdles for cancer care, and that is the genomics aspect of it. The fact we now know that cancers are due to genetic aberrations, and we now have different methods of targeting them. The next step is to collect the data. We need more patients to be on trials. We need more trials. We need more doctors to be trained to handle these trials, so that we can collect the information and then move forward.”
Are we at the maximum at the BRAS Drug Development Program for the number of trials we can conduct?
“I think we are at a good number. I think there is certainly room for more, but I think at the same time, there needs to be more staffing as well. We have Fellows coming, but we also have Fellows leaving. We are also recruiting more Staff Physicians as well. So, I think this is a good balance. But to be honest, you don’t want a centre where there are lots and lots of trials. You want a good balance, because at the end of the day, patient care comes first.”
What makes the Princess Margaret Caner Centre one of the top 5 in the world?
“I think it’s the people. It’s the fact that Princess Margaret is one of the most diversely staffed cancer centres in the World. The diversity is seen in both our training background, as well as our varying cultures, and ethnicities. I don’t think any of the larger cancer centres have such an international perspective. I also think it’s to do with Toronto itself, is a very cosmopolitan and culturally diverse city.”
When do you head home to Hong Kong?
“I am leaving at the end of December (2013). I will be starting at work in a week’s time. I will take a piece of Princess Margaret Cancer Centre and the Bras Drug Development Program home with me. And certainly there will be more collaborations with my colleagues here, and with my mentors, Drs. Siu, Philippe Bedard, Albiruni Razak, as well as Dr. Amit Oza.” “Thank you Dr. Loong. Thank you for your contribution to the Princess Margaret Cancer Centre, and the BRAS Drug Development Program, and I wish you the best of luck with your new phase 1 centre in Hong Kong.” Maggie Bras Dr. Herbert Loong has since returned to Hong Kong, and has assumed a staff position, and been appointed as an Assistant Professor in the Department of Clinical Oncology, at The Chinese University of Hong Kong (CUHK). Aside from continuing his work in drug development, he is also involved in setting up, and the administration of the newly-established Phase 1 Clinical Trials Centre at CUHK. One of the projects undertaken by him during his year as a Fellow, include the design and scripting of a patient education video on Cancer Molecular Profiling, allowing patients and their families to have a better understanding of what this process entails. This video can be viewed on the BRAS DDP website at: http://brasddp.com.
Dr. Donna Graham, Senior Clinical Research Fellow – Ireland What brought you to Princess Margaret Cancer Centre?
“I have wanted to come to Princess Margaret since I started my medical oncology training in Ireland. The physicians at the Princess Margaret Cancer Centre are world leaders in cancer treatment and research. It is where I had always hoped to work. I’ve been very fortunate to have a position with the Fellowship Program.”
Why did you wish to become a doctor?
“When I was in school, I never thought medicine was something I wanted to do, but I volunteered with patients in hospitals, and I really enjoyed that. My interest in science, and the patient experience, prompted me to apply for an undergraduate degree in medicine. It was during this time, that I became more interested in the process of how cancer occurs, and how it affects patients. I took a year out of my medical degree course, to complete a BSc in pathology, which focuses on carcinogenesis – the production of cancer. All of this, in combination with the experience of communicating with, and treating many cancer patients throughout my general medical training, led me towards a career in oncology.”
What is your work of expertise?
“I work within the BRAS Drug Development Program, and my research is focused on the two clinical research areas of head and neck cancer, and lung cancer. In addition, I am working in the Genomics Program, which is called IMPACT. IMPACT stands for: Integrated Molecular Profiling in Advanced Cancers Trial, which was established within the Bras Drug Development Program. The study allows genomic profiling, or gaining information about abnormalities of cancer genes, from tumours in different cancer sites. Much of my research is linked with another program called MATCH. In addition, I also get the opportunity to work in the COMPACT clinic, which allows cancer patients treated at other centres, access to the genomic profiling provided by the IMPACT study. We are attempting to find out more about the genetic changes within cancers, and looking at the differences between tumours that are occurring at the same time within the patient’s primary tumour. The same applies to an area where a tumour has spread to another site – which is called metastasis.” Editor’s note:
IMPACT was launched on March 1st, 2012. It is the first Canadian comprehensive molecular cancer screening program, that seeks to provide doctors with specific cancer gene information, so that each patient’s treatment can be tailored to his/her specific form of the disease. IMPACT is led by Drs. Philippe Bedard and Lillian Siu. Molecular testing for IMPACT is performed in the University Health Network Molecular Diagnostics Laboratory, at the Princess Margaret Cancer Centre, directed by Dr. Suzanne Kamel-Reid, and results from the molecular testing are included in the patient’s electronic health record. To learn more about IMPACT, please visit the 2012 newsletter on www.brasddp.com. MATCH is a Feasibility Study of Genomic Profiling Methods, and Timing of Sample Collection to Evaluate Clonal Evolution and Tumour Heterogeneity. To learn more about MATCH, please visit, www.brasddp.com under the 2012 newsletter link – author, Dr. Aaron Hansen.
Do you treat each site differently?
“Dr. Aaron Hansen’s study – MATCH - is one of the ongoing studies in the program at present, which hopes to look specifically at these questions, by assessing tumors at the time of progression or spread.”
Do you feel we are making progress in the war against cancer?
“I do. Patients are surviving for longer periods, receiving multiple lines of therapy, potentially with newer treatments, and in general, they are tolerating their treatment better. Some of the greatest impact is seen from targeting treatments to patients. Through the IMPACT and COMPACT study, our aim is to provide patients with better quality of life, and extra time with their families. This is great to see! In the Thoracic Oncology Department and the Bras Drug Development Program, we are seeing people that are living for months or years beyond what we would see traditionally. Newer therapies are being introduced, and as successful treatments become incorporated into clinical practice, we will see greater improvements in how patients live with cancer.”
What is immunotherapy?
“Some of the newer treatments are based upon the premise that cancers may evade immune system’s response. (This is one of the mechanisms by which they spread and grow.) Some of the immunotherapies essentially stimulate the immune system, so it begins to fight the cancer. We are seeing impressive responses in some of our cancer patients.” “SAVOUR, ENJOY AND APPRECIATE. LOVE HARDER, SHARE MORE, GIVE OFTEN, AND SAY, ‘THANK YOU.’” - LEE PETTERSEN
Is there any interaction with other major cancer centres in the world?
“There is on-going interaction and collaboration with multiple different cancer centres throughout the world. With many trials, we will be one of a number of treatment sites. So, in the Phase I group, we will have ongoing communication with the study sponsor, along with the other cancer centres, or sites that are also performing the studies, to discuss the specific effect that new drugs may have had on each of the patients. When a study is ongoing in multiple different sites, it is important that we do not miss the subtleties of the potential side effects of the drugs, and having a formal discussion makes all the difference. You can pick up trends that are occurring, or things that maybe we didn’t expect to see, resulting in increased understanding of the treatment. When patients are being treated with drugs for the first time, pooling the experience of multiple centres involved in the study through discussion, gives greater insight into side effects and the benefits of therapy.”
The population of any one trial globally is quite large?
“In the phase I setting, smaller numbers of patients are normally enrolled, but in later phase studies – yes. The populations may be quite large, particularly when treating common cancers. If you are trying to find a representative sample of a group of patients with breast cancer, or lung cancer; it’s such a common cancer, that you really need to look at quite a large number of patients, to see if the agent or combinations of treatments are beneficial”.
With all the cancer centres involved in one trial, who decides what treatment will be used?
“In the initial trial design, the decision is made by the Principal Investigator, which could be Princess Margaret; another site; a cooperative group, or a drug company. There will be an opportunity to discuss the design of the study prior to the study opening at our centre. As the study progresses, there may be a change or an amendment, which could change admission criteria to the study, or tests that are required, or how the study will be run. Investigators will pool their experience to discuss the best way forward with a study.”
What are some of the major advances in the last few year, and challenges?
“The advent of targeted therapy, and immunotherapies, has really expanded treatment options for cancer patients. The challenge is how we integrate cancer treatments. How do we ensure we are giving the right treatments to the right person, who will then gain a benefit from specific treatments? For each treatment administered, there may be subsets of patients who have clear benefits, and others who do not. Our aim is to select the patients, and then match them to the right drug. This is what we call personalized cancer medicine. We hope to select the patients who will benefit most, and avoid side effects for patients who are not going to gain benefit. This is a challenge for the coming years. However, treatment options for our patients are increasing all of the time. We are seeing the quality of life, and survival for patients is improving.”
Are we seeing newer cancers?
“Historically we saw cancer as a number of diseases characterised by primary site of disease. For example: Lung cancer was seen as a lung disease, until more recently. Now we see it as actually a number of different diseases. There are different mechanisms by which lung cancer develops, and subsequently, many different subsets. These can be broken down by histology, or appearance under the microscope, or by molecular changes that are present in the tumor. Treatments have been developed that will target these changes, and subsequently, groups of patients within these subsets will respond better to certain treatments. Cancer is not just one disease, it is many different diseases. This may result in new terminology for pre-existing diseases.”
What is great about working in the Bras Drug Development Program at the Princess Margaret Cancer Centre? “The Fellowship Program is excellent. I came into the Bras Drug Development Program having had no prior involvement in Phase I trials, so it is a completely new experience.
The focus on education is really impressive. I’ve learnt so much since coming here. Also the mentorship is excellent. Our mentors are available, and approachable, and provide ongoing encouragement. If there are challenges with our research, they work with us to help find the solution, and keep things moving along. This is so important. So the mentorship and support really is absolutely brilliant. I have been incredibly fortunate to have Drs. Lillian Siu, and Frances Shepherd as my mentors.” The patient exposure in this centre has been a bonus also. In other Fellowship Programs, I am not aware that Fellows receive such high levels of patient exposure. We are continually managing patients receiving specific drugs, and noticing patterns with the effects they have, some expected, and some unexpected.
Our ongoing education covers areas such as, how you set up a trial, or write up a grant. We learn about the steps involved in developing these drugs - but also we are seeing how these treatments affect patients. This is key. Having patient experience makes such a difference. We see the effects of these treatments on patients, and how they live their day-to-day lives. AND that they may actually live normal day-to-day lives! The patient exposure really makes such a difference. I will take away so much from the Fellowship Program, because I have gained such an insight into the process. I have learned so much from being involved in patient care, than I would have by reading a table of adverse events about a drug.”
What inspires you to continue on in your work?
“The patients. It is all about the impact that cancer treatment has on patients. When I see patients having improvement in their quality of life, having improvement in their survival, this is the reason I work in oncology. When something translates from pre-clinical research into clinical practice, and I start to see the improvement for patients, and I start to see the gains that are being made, then this is why I do what I do!”
How are you going to survive another Toronto winter? “I quite enjoy it. I learned to ski last year!”
What are you going to be doing at the end of your two years?
“At the end of my two years as a Fellow at the Bras Drug Development Program, I am returning to Ireland, where I will work in a Laboratory Research Program. My hope is to marry the work I carry out there, with the research I have done here. And who knows after that!” Thank you Donna. Maggie Bras
Dr. Irene Brana, Senior Clincial Research Fellow - Spain My story starts in Switzerland at the ‘Flims’ workshop. It’s the main workshop is the main workshop in Europe for training junior scientists, on how to design and conduct clinical trials. It was where I met Dr. Lillian Siu, who was the director that year. I was impressed with Dr. Siu, as she was easy to approach. I asked her how to apply to become a Fellow. Dr. Siu was quite enthusiastic about my joining the team, and two years later, shortly after I finished my residency, and fellowship in Spain, I was here! I have been a doctor since 2005, and an oncologist since 2010. At the main cancer hospital in Vall d’Hebron, I completed 4 years of residency, and one year of fellowship in drug development. I worked as a resident in all types of tumours, but mainly in the drug development program fellowship, which is similar to what I do in the Bras Drug Development Program. When I told my bosses in Spain that I met Dr. Lillian Siu, and we had been talking about my coming to Toronto to do a Fellowship at the Bras Drug Development Program, at the Princess Margaret in Toronto, they told me: “Don’t look for anything else! Just go there. This is one of the best hospitals around the world, and this is one of the best drug development programs. You are not going to get better training anywhere else.” And so my choice was clear. I was not going to look for anything else! What is interesting about the North American centres, especially Princess Margaret, is the good balance in terms of clinical and research workload. I believe to be a good clinical scientist, you must have both. Clinical research is first and foremost, to benefit your patient. When working with a patient, you ask the question: How can we improve the treatment for this patient? This question inspires me. On an average day, along with the clinical workload, our research workload is in designing clinical trials, and designing the translational research studies related to clinical trials, which means understanding why some patients respond to treatment, while other patients do not. Coming here has given me great opportunities to interact with some of the scientists from a higher cancer institute. My patients give me inspiration. My mentor in Spain once told me: “Drug development is what you should do in your life Irene. Every day you see patients who do not respond well with their treatment. You, Irene, cannot see patients every day, and not do anything to improve their lives.” We need to improve. We need to do things better. We need to find a solution to cancer, and the only way we are going to find the solution, is through research. Finding better drugs, and better ways to administer to our patients. My fellowship at Bras Drug Development Program is for three years. I have been here for two years and I am lucky that I am going to continue for another year! I am really excited about this. At the end of my fellowship, the plan is for me to go back to Spain, and to establish a relationship between two great programs. I would love to stay longer. I love it here. I am really happy with the environment at Princess Margaret, especially the BRAS Drug Development Program. Canada is a great country to live in. It has been a wonderful experience. Thank you Irene. Maggie Bras
Here’s to our heroes of yesterday, today and tomorrow. We honour you. “A TERMINAL ILLNESS IS A WAKE UP CALL TO LIVE, REALLY LIVE.” – LEE PETTERSEN
Valerie Bowering, and Lee Pettersen
“My story begins in June of 2008, in a way that is familiar to many of you. I was married to a great guy living a pretty normal life. Leif was a former CFL football player, as well as a TSN broadcaster. He was a star, and I played a supporting role as Mom, driver of children, gardener, and renovation diva. When a friend called to ask if I would join the Ride to Conquer Cancer in support of a pal recently diagnosed with cancer, I said, absolutely. Niagara Falls didn’t seem that far by car, and I had ridden a bike when the girls were small. That phone call changed my life forever. Leif’s words of encouragement were forever etched in my brain. He said: “Are you nuts?” I became a Biker Babe, stronger, mentally and physically, and I was healthy, or so I thought. Six weeks later, Leif died of a heart attack. He was 57. With the help of family, friends and my little blue Trek road bike, which Leif had surprised me with, I cried and rode my way through the shock and grief. By the following spring, I was starting to feel normal again; skiing, laughing and spending time with amazingly supportive friends. In March of 2009, seven and a half months later, that all changed at my annual physical. In a heartbeat I became ‘Mom who has cancer – a terminal cancer’. It was a terrible, chaotic time. I worried about my girls and how they were going to manage without parents, and I had a horrible thought; I would never be able to wear the gorgeous red Italian shoes I had purchased the day before! A shrink would have a field day with that one! The next few days were filled with tears, and even a few laughs as I prepared to die – even so far as cleaning out my underwear drawer – that is kind of a girl thing! Off I went to Princess Margaret Cancer Centre for my introductory visit. The first doctor who examined me, asked: “Why do you think you are at Princess Margaret?” I replied: “Because I’m a goner; I have ovarian cancer and I only have a few weeks to live.” He was quite startled and said: “We don’t use that term here”. He then said that he had seen many very sick people, and I was going to be around a lot longer than 2
weeks! It was the beginning of my love for Princess Margaret. I had walked in without a future, and walked out with HOPE. When I walked into Dr. Joan Murphy’s office at Princess Margaret in March of 2009, I was the typical, terrified, ‘deer in the headlights’ patient - frozen in fear. My life was already in chaos, with the death of my husband preceding my diagnosis by a mere 8 months. I had listened to the accolades thrown his way, and the recitation of his accomplishments and contributions, and I had decided that if I died then and there, I would be anonymous. I had done little more than go to work and raise two lovely daughters. After Leif’s death, I vowed to change that. This cancer business was definitely a monkey wrench in my new life plan. So there I was, sitting across from Dr. Murphy, totally convinced I was a goner. There would be no Christmas for me in 2009. But Dr. Murphy changed all that. On April 1st, 2009, she and her team of skilled accomplices set about to snip and toss, and cut and throw away every single bit of cancer they could find, closed me up and started me on my first round of six rounds of chemotherapy – my journey of HOPE. Have I mentioned Zain up in the Wig Salon at Princess Margaret? For a woman with long blonde hair, and a slew of healthy friends, hair loss was very BIG, but when I met Zain, my fear disappeared. He walked me out of the salon with a gorgeous wig, which took the patient out of the mirror and put Lee back in it. Mid June, I participated in my first Ride to Conquer Cancer as a patient, in the middle of my chemotherapy. Why did I do that? Because Dr. Joan Murphy, a fellow cyclist, said to me: “Just do it!” She kick started my life as a cancer patient, and my strong belief in looking ahead for the pinprick of light, instead of looking down into the darkness. The 2009 and 2010 rides were in the middle of my chemo, but both were doable, thanks to the support of my fabulous team, and the knowledge that I was doing something to help myself – to help find that magic elixir that would prolong my life. And that is what the Ride to Conquer Cancer means to me. There is a moment in time from the 2009 ride that stands out. I was riding along, with my head down, taking it easy, when I started up THAT hill – the legendary hill from the first ride. I really didn’t see how I was going to make it on my bike, or even by foot. Then I felt a hand on my back. Teammate, Doug Palmer, a two time cancer survivor, had come back down from THAT hill, placed his hand on my back, and pushed me all the way up! April 2nd, 2010, I was officially a one year cancer survivor! I was feeling better than ever. I was happy, healthy and doing every possible thing a normal person does. It made me want to leap about hugging and kissing everyone. I was living my life to the fullest. Every day, I will never have a regret that I have wasted a moment or an opportunity. In the last several months, I had been to Florida, Turkey, and to Vancouver to
“BY HAVING REVERENCE FOR LIFE, WE ENTER INTO A SPIRITUAL RELATION WITH THE WORLD. BY PRACTICING REVERENCE FOR LIFE, WE BECOME GOOD, DEEP AND ALIVE.” - ALBERT SCHWEITZER
attend the Olympics. I had been to Puerto Vallarta, and in two weeks I was flying to Arizona, to try my hand at being a cowgirl for a week at a dude ranch. No pity parties for me please. In May of 2010, when my cancer got busy again, I left Dr. Murphy’s care and headed over to the BRAS Drug Development centre. When I said ‘goodbye’, I promised Dr. Murphy I would live a ‘three for one’ lifestyle. If I had a chance to live up to five years, I reasoned, I wanted it to feel like fifteen. She agreed with that theory, and urged me to come out of the gate running; to travel and laugh and dance, to wear my red shoes at every opportunity, and that is how I am living my life now. Squeezing every drop of joy out of each day. I sat across from Dr. Amit Oza of the Bras Drug Development Program, wanting to shout out: “I have serious ovarian cancer”. I was scared. As Dr. Oza shares with me the soon to be announced clinical trial, for which I am, thankfully a candidate, I numbly listen trying to think of good questions to ask. I really wanted to ask if there was a chance of a cure, but I did not. If you are not sure you are going to like the answer, never ask the question! I have been absorbing all the information that Dr. Oza presented, and like a dog with a bone, I grabbed onto the phrase – ‘because you are fit’, which seemed to precede the list of clinical trials coming up. On June 1st, 2010, I entered my first clinical trial. I was in the control arm of the trial, where I received the standard drug. I was okay in the control arm, because as Dr. Oza explained, the drug looked very promising, and might be offered to patients in the control arm later on compassionate grounds. The treatment did reduce my tumours by 30%, but by July 2011, the growth crept up again, so I was off the trial. We opted to wait and watch. The next clinical trial I entered in November of 2011, was the MK1775 trial, made available due to testing of my tumour tissue, which revealed a mutated P53 gene. I was not in the control arm of this trial. The trial kept the cancer in a low level of activity for nine months, but I was losing weight, as I had difficulty eating, and keeping down the little I did consume. At the end of nine months, my CA 125 began to slowly climb, indicating increased activity. In August of 2012, Dr. Oza offered me an opportunity to enter a phase 111 randomized double blind trial. I was given Taxol
plus AMG386/placebo weekly, and my symptoms began to subside immediately. I felt better, allowing me to enjoy the best possible quality of life, with loads of energy. I now ski, snowshoe, hike, ride horses, travel extensively and cycle regularly, as I train for my 7th 200km Ride to Conquer Cancer. This trial has given me one and a half wonderful years. I realize it will not ‘cure’ my cancer, but I believe in the eighteen months since I began this trial, more promising treatments are in the works. It is because of, and thanks to the ongoing research, much of which has been funded with dollars raised by events, such as: the Ride to Conquer Cancer, the Run or Walk to Conquer Cancer, Road Hockey to Conquer Cancer and the Believe in Fashion show for the BRAS Drug Development Program, that I am alive today. The key ingredient in this story is HOPE. I get a big dose of HOPE with every single visit. Dr. Amit Oza, my oncologist; Gerry Prendergast, and Valerie Bowering, my clinical trials nurses’ and team, ‘shine’ in the hope department. Never forget: Hope fuels the drive to survive. Well here we are five years after my mega surgery, and the removal of many body parts, and attachments. I have never once felt lonely, without help, or helpless, and the one word that keeps coming to my mind, is gratitude. I am so very lucky. I have the most incredible family, a man in my life whom I love deeply, and who loves me in return. I have waves upon waves of friends. Since I go to Princess Margaret weekly, I have made new friends there as well. Fellow patients in the same clinical trials, with whom I compare results and share hope; lab technicians who take my blood, tell me about their families, and ask about life at Blue Mountain; chemo daycare nurses, manning the ‘spa chairs’, are absolutely over the top wonderful, and I often ask if they can arrange a manicure/pedicure while I am in for the day! Cancer doesn’t even get to own me those four hours in the chair, thanks to those lovely, kind people. I realize my life is full of such extraordinary people. I have already lived the richest most rewarding life possible, and every extra day is simply gravy. The trial I am on has given me so much: I am symptom free, I have hope and I have my life back.”
no other sign that pinpoints this cancer.” Dr. Siu said that there was not really much that she could do. “As long as your tumour is asleep, we want to keep it asleep, because your time is very short.” Bobbi didn’t want to die, and asked Dr. Siu: “Please do something.” Authors note: ‘Pancreatic islet cell’ cancer belongs to a group of cancers called ‘neuroendocrine tumors’, and Dr. Lillian Siu was the North American Chair of the Neuroendocrine Tumor Task Force. Bobbi was in good hands.
Dr. Lillian Siu and Bobbi Pfisherer-Cohen
Bobbi has cancer. This is her story: It was 8 years ago that Bobbi’s life changed. She didn’t feel well, but couldn’t pinpoint why. Blood work was done, showing nothing abnormal. A high fever took her into the emergency department days later. Again, her blood work was normal, but a CT scan showed something odd with her liver, so off she went to see a specialist at a Toronto downtown hospital. She was told she was perfectly fine, with some abnormalities in her liver, nothing specific, but otherwise perfectly healthy. Bobbi told the doctor, “but I am so tired all the time”, only to be told she was okay. “But weeks later, I received a call from the doctor, who said that there is an associate of mine who thinks there is something more to this, and we think you should come back in. I went back in for more tests, and then was told: Rest assured, you do not have cancer. Go home and enjoy Christmas. But days later they called me back in to do a biopsy, and this was when I was told I had ‘islet cell’ cancer!” Bobbi was told she had 3 months to live! Immediately Bobbi went into emergency mode. Minutes after her diagnosis, she called her friend, and gave her a mission. “Find the best oncologist in the city who treats ‘islet’ tumours”. Within the hour she had a name. Dr. Lillian Siu of the BRAS Drug Development Program at the Princess Margaret Cancer Centre! “The fact that I was terminally ill, with three months to live, freaked me out more than the actual label of ‘islet’ tumour”, says Bobbi. Days after her diagnosis, Bobbi was sitting across from Dr. Lillian Siu, who she describes as very warm and very caring. Dr. Siu told Bobbi her cancer is very rare, and is terminal. She went on to explain what an ‘islet’ tumour was: “Your tumour is called ‘pancreatic islet cell’ cancer. It is located in the back of the pancreas, and it is asleep. There is no point removing it surgically, as the primary tumor is in the pancreas, and it has already spread to involve almost 90% of your liver. We do not know how long the primary tumour has been there, but obviously it has had time to cause a great deal of damage. The only symptoms you have right now are fatigue. There is
Not long after that, Dr. Siu called Bobbi into her office to say: “I think I’ve got a drug for you that we can try; it is a drug trial, and if your one of the lucky ones, you can live for five more years. If you are not one of the lucky ones, it is anywhere from zero to five.” Bobbi said: “OKAY. Let’s Go!” Authors note: The BRAS Drug Development Program conducts early phase clinical trials, involving patients with advanced cancers, using new tools to identify their genetic ‘fingerprint’. To date over 5,000 patients have gone through the BRAS Drug Development Program! Bobbi set goals for herself. She didn’t think to herself, why me, or why am I going to die? No, Bobbi thought about her daughter who she wanted to see grow up into a beautiful young woman. “So I started focusing on goals”, said Bobbi: “ I would live until my daughter had her Bat Mitzvah; I would live until she graduated from Grade 8; I would live until she got into grade 9; I would live until she graduated from grade 12, and if everything was fine with me, I would get her into University!” Bobbi chose not to tell her daughter that she had cancer, or that she was dying. No, Bobbi chose to live her life as normal as possible. “I had this idea, that if I kept my life as normal as possible, I would live on! I worked full time at the Bay Crest Centre for Geriatric Care. I worked with seniors and I loved my job. I worked with the Rabbi, and so I worked a lot of religious holidays, and it kept me busy. I found it helped to keep me psychologically safe as well. It was my therapy, in addition, to my therapy with the psychiatry department at PMCC. Dr. Siu was also a major source of support, along with my study nurse and her team.” Bobbi sent her daughter to a psychiatrist, to help her deal with what was going on at home. She reacted by telling Bobbi: “Mom, I don’t need this therapy, I am perfectly okay.” Bobbi responded: “Yes honey, you are perfectly okay, but I am the one who is sick, and I worry about you reacting to me with the pain I have in my liver; or the fact that I am vomiting; or the fact that I have diarrhea; or the fact that I cannot eat the way I used to; and look my hair is falling out, and I am really embarrassed about that.” And she said: “Yes, I think you should get a wig!” From that moment on, when Bobbi went out of the house, she had to wear her wig, so as not to cause embarrassment to her daughter. As for Bobbi’s husband, he was devastated by her prognosis, and was not handling her illness well. “My husband had great difficulty with my cancer, and he kind of withdrew from my
“LIVE YOUR LIFE FROM YOUR HEART. SHARE FROM YOUR HEART AND YOUR STORY WILL TOUCH AND HEAL PEOPLE’S SOULS.’” - MELODY BEATTIE
daughter and me. We tried to get him support, which he did, and then it took him about a year and a half before he came emotionally back into the family. But my daughter noticed it, and I told her: “You know Daddy is having a hard time with me being sick.” And she said: “Yes, but Dad’s do that!” I have an incredible 14 year old!” Bobbi had a lot to cope with while trying to stay alive!
Part III Bobbi wanted to create memories for her daughter, so she started a journal. In it she wrote: “You know by the time you read this, I will have passed away. It was my decision when you were small not to tell you I had cancer, and as a parent, I have a right to do this. When you read this, you may be in your teens, and you may be angry with me for not telling you, but you’re going to have to live with that. I could just as easily have been hit by a car, and you would suddenly be told that your Mommy died in the emergency room!” In the 8 years she was never supposed to have, Bobbi and her family have created a lot of memories. “We went away this past January for two weeks”, said Bobbi. “We have gone on summer vacations; we did a lot of things together, and I would say to my daughter: You know, just think of the kind of day it was today, so when you are with your own kids, you will say, yes, I did that with my Mom, or I did that with my parents, and those are the kind of memories I want you to have. I didn’t want to overdo it, or over play it, but I felt it was important that she knew that we did a lot of things together. We have been doing that. This has been our life for the past 8 years.” Dr. Lillian Siu: “Bobbi has a cancer that has responded well to the treatment she received. It really is a credit to the advances in our field, and knowledge, which allow this to happen.”
Part IV As Bobbi talked about the last years of living with cancer, she revealed the pain, the challenges, the victories, and her continued hope for life to come. Bobbi continued her story: “Dr. Siu said that she knew me well enough, that I do not tolerate medications well, but because I was enrolled in a clinical trial, all patients have to start at the full medicating dose, even though Dr. Siu thought I would do very well on a lowered dose.” “And you know what? She was absolutely right! I’ve been on this low dose for almost a year. The results have been phenomenal. My tumours, both the primary and the ones in my liver, has shrunk 47%, which is extraordinary! They would never have expected it. I mean, this is what they would expect at the highest
dosage level. And they have achieved that with me! So even if the drug is horrific to deal with, it’s a choice, and I would rather obviously have all the side effects, and be alive, than not be here to be with my family.” “During all of this, I think the tie to Dr. Siu, Dr. Miller, who is the psychiatrist I see here, and Jennifer my study nurse, it is just a really strong bond. A really strong triangle. I always felt support, no matter where I was. If I went down to Florida, if I went away to Europe, we always had a plan, so that I knew I could reach them at any time. I am always reassured. They let me live my life. I have no control over what is going on inside my body, and I can get sick tomorrow, and then my life is over. But I’ve been very fortunate that I’ve lived a good 8 years, and I’ve often thought, that when you hear the word cancer, it’s horrific, and then I think why did I have this kind of cancer, versus any other kind of cancer? But in hindsight, I think I am fortunate to have this kind of cancer, because it is asleep, and it has let me live a really good life. It has given me a healthier outlook. It has given me a much fuller life, because I look at life each day as wonderful! It has been a good experience, even though it has been a scary one. And I really feel I’ve gotten through it because of Dr. Siu. I think that if I’ve had to have any kind of cancer, I am okay with having this rare islet cancer. Dr. Siu is one of the most foremost people on it. I know that if there is some other drug out there, she will find it for me. Dr. Siu said if I were lucky, I would have two years on this drug, and after that, something else would be found for me. I believe her. So my hope goes on. And I’ve often thought that I am unfortunate there is not enough research being done with this kind of cancer, but I know it is so rare, and there are so few people with this. I know I was lucky that I was diagnosed when I was, because I was relatively young, and I’ve always been healthy, and I think those are the two main factors in being able to get to the place that I am now. This is one of the positives about this illness, is that I came in at a time when I could be helped. I’ve heard stories of people being on ten to twelve drug trials, and this is only my second, and it’s been remarkable, and in both cases I’ve had a positive outcome. The first drug trial, my tumours shrank, certainly not as much as they have now, and when the medications stopped working in the first trial, the tumours grew back. And so, as I have said, having 47% shrinkage is quite remarkable. Yes, two drug trials and this is where I am 8 years later. I am healthy and I am lucky.” Thank you Bobbi. Maggie Bras
Princess Margaret Cancer Centre
What is Cancer Genomics? All cancers arise from changes that occur in the DNA of cells. DNA is the chemical set of instructions inside each cell that tells the cell what to do. The complete set of DNA within a species is called the genome. When the DNA instructions have mistakes in them, cells may not function normally and may grow out of control, causing cancer. The study of genes associated with cancer is referred to as cancer genomics. Cancer-causing changes in DNA, called mutations, can be inherited but most are acquired throughout life. While cancer was once thought of as a single disease that affected many different parts of the body, researchers now know that there are differences in the DNA makeup of cancer cells of each patient, and that changes in the cancer’s DNA can cause each cancer to have a unique behaviour. That’s why two patients who have cancer in the same part of the body may respond differently to the same treatment. It’s all in the genes! The mission of the Cancer Genomics Program (CGP) at the Princess Margaret is to advance personalized cancer medicine, through the identification of underlying genetic mutations, and molecular mechanisms that drive cancer, and to match patients to targeted therapies based on the genetic makeup of their specific cancer. Testing for mutations in cancer cells is known as molecular profiling, and in March 2012, the CGP opened its first comprehensive molecular profiling study, IMPACT (Integrated Molecular Profiling in Advanced Cancers Trial). IMPACT provides state-of-the art molecular profiling of cancer tumours to Princess Margaret patients, who are currently receiving cancer care for selected advanced cancers. In November 2012, the CGP also opened a parallel study called COMPACT (Community Oncology Molecular Profiling in Advanced Cancers Trial), which offers molecular profiling to patients who are currently receiving cancer care outside of the Princess Margaret. Patients who are interested in participating in COMPACT, are referred to the Princess Margaret by their community oncologist and seen in the COMPACT Clinic, a weekly clinic run by CGP staff oncologists. IMPACT and COMPACT recruit up to 1000 and 500 patients per year, respectively. To date, 1517 patients have been enrolled, and 1131 tumour specimens have been molecularly profiled through these studies. All molecular profiling results are included in the patient’s University Health Network electronic health record and, in the case of COMPACT, results are also faxed back to the patient’s community oncologist. Molecular profiling results are discussed at multi-disciplinary Genomic Tumour Board Meetings where Princess Margaret doctors, scientists, and other health care team members, gather to provide input from their different specialities, and propose a personalized treatment plan that is tailored to each patient. By looking at the molecular profile of many tumour samples from many different patients, we will be able to gain a better understanding of what makes one cancer different from another, which is important, because it will help explain why two patients with the same type of cancer may respond very differently to the same treatment. By connecting specific genomic changes with specific outcomes, we will be able to develop more effective and individualized ways of treating each cancer patient. For more information on this exciting initiative, please contact the lead investigators, Dr. Philippe Bedard (philippe.bedard@ uhn.ca) and Dr. Lillian Siu (Lillian.email@example.com), or the CGP Program Manager, Celeste Yu (firstname.lastname@example.org). A telephone hotline has also been set up for IMPACT: (416) 946-2993. Celeste Yu Program Manager Cancer Genomics Program Princess Margaret Cancer Centre
CANCER GENOMICS TEAM – IMPACT 2014 Front: Djamel Haribi; Celeste Yu, Dr. Philippe Bedard; Dr. Lillian Siu; Dr. Trevor Pugh; Dr. Suzanne Kamel-Reid; Dr. Tracy Stockley; Tong Zhang Middle: Helen Chow, Geeta Krishna, Amanda Giesler, Dr. Anna Spreafico, Dr. Mahadeo Sukhai, Vanessa Speers; Yali Xuan; Natalie Boruvka; Michelle Mah Back: Lailah Ahmed, Katherine McDonald; Breanne Swayne; Anastassiya Soboleva; Justin De Souza; Dr. Mariam Thomas; Nadia Amin; Maggie Zhou
Why Is Immune Therapy Now Showing Promise? For more than a hundred years, it has been recognized that cancers develop in the context of the immune system. Unlike conventional cancer therapies, the idea behind immune-based therapies is to kill cancer cells with the accuracy of the immune system while sparing healthy tissues. Immune-based therapies can induce long-lasting responses and prevent the development of treatment-resistant disease. Moreover, as the cancer evolves and develops new mutations, the immune system is adaptable such that it has the ability to recognize and attack these new cancer mutations. Only until recently, however, immune-based therapies held more promise than success. While occasional dramatic responses to immune therapies were observed, these were rare occurrences and were typically limited to a few kinds of cancers. Immune Therapy of cancer remained an important academic pursuit, but many doubted that it would ever lead to real advances in the treatment of patients. After decades of disappointment, the tide has finally changed. One of the challenges hindering the initial development of Immune Therapy was that the immune response to tumors was poorly understood. In the last several years, however, several important breakthroughs have occurred; many of which were made at the Princess Margaret. Insights into a subset of immune cells which are capable of fighting cancer, called T cells, have led to a better understanding of how these cells are able to recognize and attack tumors. It is now clear that the tumor is able to dampen the ability of T cells to clear the tumor, and we are beginning to unravel ways we can manipulate T cells to overcome this suppression. For a cancer to develop in a patient it must either hide from the immune system so that an immune response never develops, or the cancer must figure out a way to block the ability of T cells to target and kill the cancer. In the last few decades, many of these mechanisms have been revealed, and therapies that harness the power of the immune system to fight cancer focus on either 1) boosting the anti-cancer response, 2) blocking the ability of tumours to suppress the immune system, or 3) a combination of both strategies. At the Princess Margaret Cancer Centre, the Immune Therapy Program and Bras Drug Development Program have brought together internationally respected experts in the fields of immunology, cancer, medicine, pathology and surgery, to aggressively move immune research from the lab into clinical trials. Major advances have already been made in clinical immune therapy for cancer and have resulted in the approval of ipilimumab for melanoma. Ipilimumab blocks CTLA-4, a molecule whose function in the suppression of immune responses was first described at Princess Margaret in the laboratory of Dr. Tak Mak. Other drugs that target other immune checkpoint inhibitors, such as PD-1/PD-L1 inhibitors, are under active study at the Princess Margaret in a variety of cancers. Another promising way to promote an anti-cancer response is to grow up large numbers of the cancer-fighting T cells in the laboratory that are then infused into patients as a treatment. One approach involves coaxing T cells found within a tumor mass which are activated and expanded in the laboratory. This approach has resulted in high response rates in melanoma patients treated with this regime. At the Princess Margaret, a team lead by Drs. Pamela Ohashi and Linh Nguyen has established the expertise needed to harvest and grow these cancer fighting cells known as tumor-infiltrating lymphocytes. A clinical trial in melanoma patients is ongoing and will be extended to additional trials in ovarian cancer and mesothelioma. Also, in the cell therapy arena, Princess Margaret investigators Drs. Marcus Butler and Naoto Hirano have developed a T cell manufacturing system that starts with a blood draw rather than a tumor biopsy. Building on prior success in an early phase clinical trial at the Dana-Farber in Boston, they are planning a series of immune therapy trials that combine their tumor fighting T cells with other immune treatments. They have also obtained an initial commitment to bring gene-engineered T cell trials to the Princess Margaret in collaboration with an industrial partner. Despite the challenges ahead, there is renewed enthusiasm for the Immune Therapy of cancer. There is much more to learn, but we now have the basic tools to begin understanding how new immune treatments impact the immune response and fight against cancer. By understanding the impact of these therapies on how the immune system is able to recognize and eliminate cancer, we hope to develop better, long-lasting treatments.
Dr. Pamela Ohashi, PhD Director of Immune Therapy Program Co-Director Campbell Family Institute for Breast Cancer Research Senior Scientist, Princess Margaret Cancer Centre Dr. Marcus Butler, MD Medical Oncologist Director Immune Monitoring Laboratory Immune Therapy Program Princess Margaret Cancer Centre â€œONE OF THE MOST COMMON CAUSES OF FAILURE, IS THE HABIT OF QUITTING WHEN ONE IS OVERTAKEN BY TEMPORARY DEFEAT.â€? â€“ NAPOLEAN HILL
The BRAS Drug Development Program Team - Who we are and what we do. The BRAS Drug Development Program at the Princess Margaret Cancer Centre is home to a passionate and dedicated team of investigators, scientists, coordinators, research fellows, administrative staff, research assistants, and specialized oncology nurses working in clinical research, who help provide access to new anticancer drugs in development. The team works alongside several other departments within the cancer centre, such as the Cancer Clinical Research Unit (CCRU); the Research Ethics Board (REB); UHN Pharmacy; and Departments in Laboratory Medicine, Radiology, Pathology, Correlative, Ambulatory Care, Systemic and Transfusion unit, and in-patient units, to name just a few. The research team collaborates closely with many groups outside of the Princess Margaret Cancer Centre, including the National Cancer Institute (NCI), National Cancer Institute of Canada Clinical Trials Group, and the Ontario Cancer Research Ethics board (OCREB) and pharmaceutical companies or sponsors. Patients may not meet all the members of the research team during their visits, as many team members work behind the scenes, to ensure clinical trials are conducted to the highest of standards. Each team member actively contributes, to ensure quality patient care, and data for each clinical trial in which we participate. There are many members of the “research team” that to elaborate on each member and their vital role, would take up the entire newsletter! Listed are a few of our members, and a brief overview of how they contribute to the cutting-edge research being conducted through the BRAS Drug Development Program. Principal Investigator: The principal investigator, or PI, is a physician who takes on the responsibility of running the clinical trial. This responsibility includes providing patient care, ensuring the trials are conducted according to Good Clinical Practice (GCP), and adhering to hospital policies. The PI oversees not only patient care, but also the conduct of the research being done within Princess Margaret and at other centers that are affiliated with the Princess Margaret Consortium. Importantly, another facet of their responsibility, includes working closely with clinical team members, statisticians and other participating PIs, to analyze clinical trial findings, and how this new information may positively impact or change clinical care. Co-investigator or Sub-investigator: Working alongside the Principal Investigator, this is a group of physicians that share in the responsibility of conducting clinical trials.
Who Takes Care of Clinical Trials Data? Data Coordinators are responsible for the collection, analysis, and verification of information that has been collected in a clinical trial. This group of people develops tools, prepare documents, and work with the hospital’s Research Ethics Board (REB), the Ontario Cancer Research Ethics Board (OCERB), and sponsor of the study, to ensure all documents are approved for use in the clinical trial. An example of these documents is the informed consent forms, which each patient signs prior to enrolling onto study, as well as the many worksheets that are used to capture the data for study. Data Coordinators are extremely organized, and have an eye for detail, which is critical when conducting clinical trials. Clinical Research Fellows are physicians who have received all their necessary training in oncology, but are enthusiastic to learn about drug development. This means that they spend an extra two-years learning and specializing in the ‘in’s and outs’ of drug development. As Canada’s largest cancer centre, Princess Margaret is a teaching hospital, and world renowned for its research. As such, physicians from all over the world apply to Research Fellowships which will allow them to work alongside globally respected physicians, collaborating on research projects, expanding their knowledge and experience in research, clinical trials, and generalized oncology care. They not only see patients within the hospital setting, but they also learn the behind the scenes of research. Administrative Staff are the men and women that work within the multidisciplinary team to provide the administrative assistance, which is necessary to keep a large group functioning. They collaborate with many different groups not only within Princess Margaret Cancer Centre, but externally as well; to plan, organize and ensure the daily operations of the program run smoothly. They are often assist patients and their families with any questions or concerns they may have. Clinical Research Coordinator III (CRCIII) are Specialized Oncology Nurses practicing in clinical research, which have undergone extensive oncology nursing, and clinical research training. They are the front line staff providing care for patients in the
clinic setting; some of the responsibilities include consenting patients to participate in the clinical trial, screening for eligibility, assessments and treatment of patients; all the while collecting data that is required for the clinical trial. They teach and support patients and their families physically, mentally and emotionally, all while following the study protocol. They coordinate the many study appointments, and ensure all appointments are within required timelines, and help patients navigate through the hospital system. Some CRC III’s administer the study medications to patients as well. Many clinical trials require blood or tissue samples to be taken, and Princess Margaret Cancer Centre has specialized oncology nurses who collect these time sensitive samples. only within Princess Margaret Cancer Centre, but externally as well; to plan, organize and ensure the daily operations of the program run smoothly. They are often assist patients and their families with any questions or concerns they may have. Clinical Research Coordinator III (CRCIII) are Specialized Oncology Nurses practicing in clinical research, which have undergone extensive oncology nursing, and clinical research training. They are the front line staff providing care for patients in the clinic setting; some of the responsibilities include consenting patients to participate in the clinical trial, screening for eligibility, assessments and treatment of patients; all the while collecting data that is required for the clinical trial. They teach and support patients and their families physically, mentally and emotionally, all while following the study protocol. They coordinate the many study appointments, and ensure all appointments are within required timelines, and help patients navigate through the hospital system. Some CRC III’s administer the study medications to patients as well. Many clinical trials require blood or tissue samples to be taken, and Princess Margaret Cancer Centre has specialized oncology nurses who collect these time sensitive samples. Our Patients are dedicated, courageous and inspiring. We have the honour and privilege of getting to know them, their families and their story. They truly are the most important members of the team, as we work together to “Conquer Cancer in Our Lifetime”. Valerie Bowering RN CON(C) Clinical Research Coordinator III Special thanks to Chantale Blattler, Pamela Degendorfer, Marcia Flynn-Post and Katherine Karakasis
Leslie Williams, BSc, BScN, RN MN (Student) Advanced Practice Nurse Educator-CCRU Princess Margaret Cancer Centre. Leslie Williams is a registered nurse. She is completing her Masters of Nursing at the University of Toronto, with a research focus on the social determinants of health in marginalized groups. Her short term aspiration, is to apply to the Nurse Practitioner Program. Leslie holds a previous degree from McMaster University in Science, with a focus on biology/biochemistry. Leslie is a mother of 2 young children, and has volunteered for many years in Central and South America. Leslie was born in Canada, and is a Nurse Educator for specialized oncology nurses in clinical trials.
What Is A Clinical Trial Educator? “As a nurse educator in clinical trials, I work closely with the nurse manager, Marcie Flynn-Post, and education specialist Lindsay Philip and Alex Kerr. I provide critical research education to clinical research coordinators. With the increasing complexities of clinical trials within the BRAS Drug Development Program, at the Princess Margaret Cancer Centre, adhering to good clinical practice, and producing excellent quality data, requires ongoing education for everyone working in research. Therefore, our education team assists the various research teams, to gain the knowledge and skills required to conduct clinical research studies.”
Why A Clinical Trial Educator? “Originally I was a Clinical Trials Nurse in Neuro-oncology in the Gerry and Nancy Pencer Brian Tumour Centre, with Dr. Warren Mason. I was in this role for 8 years. I was interested in trying something different, and when I was approached about this position while pregnant with my 2nd child, and given how important the role is, I felt that they really should be looking for someone who was not going on maternity leave in 6 months! When I was coming off maternity leave, the position was still open, and it was then that I contacted Marci to learn more about the position. I thought it was an exciting opportunity. Here I am!” “SQUEEZE EVERY DROP OF JOY OUT OF EACH DAY. DO NOT WAIT TO LIVE YOUR LIFE – TOMORROW IS NOT GUARANTEED FOR ANYONE.’”– LEE PETTERSEN
Why Oncology? Oncology is such a difficult journey, and to just be able to provide holistic care, is something that I enjoy doing. I don’t just look at the disease, I look at the whole journey for the patients. You end up bonding with the patient’s family; you understand how hard it is for the family members as well, so at least the way I nurse, it is more like a ‘family care centre’. Oncology is always changing, and I love science. The nice thing about the drug development program, is there are always new agents. You never know when you might come across one that can really prolong a patient’s life, while increasing the quality of their life. I think until someone kicks me out, I will always be here.
What Inspires You? “It is the patient interaction. It is very different for me, as I am now in education. I love working with my nursing colleagues. They’ve been fantastic, and just seeing the quality of care they give their patients, while adhering to very stringent protocol requirements, inspires me. The fact that they can take very important requirements, and then deliver it in a way that is therapeutic, is wonderful. They just don’t see the patient as a subject, but they see the patient as a human being. Developing that relationship, I find inspiring. That is the part I miss, because I used to do it every day. But now when I am with nurses that are going through the orientation piece, I find myself saying – “I’ll come to the clinic with you”, so I can still get some of that interaction.”
Why Are You Here At The Princess Margaret Cancer Centre? Oh this hospital has a reputation for innovative science, excellent therapeutic care. It speaks for itself. Princess Margaret! When I first got hired here, I always just assumed that only the smartest and brightest scientist, and brightest nurses, get accepted into this hospital. I would say every career educational milestone I have made, has been because I’ve been inspired by physicians and nurses who have worked here. I would not have met any of my objectives, be it academically or the career path I am on, if I wasn’t here at Princess Margaret. The Pencer Centre was a fantastic work environment, and just seeing all of the advances they were making, it just inspired me to want to jump on board, and to put the evidence into practice. They’ve been supportive. They were even supportive when I said I wanted to go into an educational role. They said: “It’s fantastic; you’d be great and yes!””
You Obviously Get Emotionally Involved With Your Patients And Their Families: Yes, I do take it home. I think a lot of that has to do with my personality. I invest a lot into my job, and my relationships with my colleagues, and definitely my relationship with my patients. I think because I worked in the brain tumour centre – the diagnosis and prognosis is very grim, that I’ve learned to invest in my patients, and let them know that we’ll care for them, and make their end of life experiences as comfortable as possible. But, I’ve learned that when I take it home, I want to celebrate life! I have two young children, and they are such a blessing, so I focus on that. Yes, one life might have ended, but we are still procreating life, and if we invest in science, and if we invest in new drugs, then maybe we can eradicate cancer globally. Thank you Leslie. Maggie Bras
Bernadette Southwood, BScN, CON(C) Clinical Trials Nurse BRAS Drug Development Program What brought you into medicine? In kindergarten, I used to watch Dr. Kildare, and he inspired me to become a nurse. I always asked for the newest and greatest nursing kit out of the Sears catalogue. Helping people is what I love. I was hired by Princess Margaret upon graduation in 1993, with a Bachelor of Science in Nursing from Ryerson University. My first position started out as a relief nurse in each of the clinics within the hospital. I inhaled everything I could learn. I enjoyed it, and I loved the patients. My next position was in 1995, when I moved into Chemo Daycare, now called the Systemic Therapy Unit. This is where I honed my IV skills and chemo administration skills.
When did you being working at the BRAS DDP as a Clinical Trials Nurse and what is a typical day like for you? I came to the BRAS DDP in 2001. A typical day will see me entering bloods; seeing my patients in clinic; seeing them through to chemotherapy; making sure they are okay, that they are well enough to receive their chemotherapy; triaging when a patient phones in when they are having trouble at home, and whether to send them on to emergency or bring them in here. Busy day. As a clinical trials nurse, I am called to the clinic by the doctor, who identifies the patients who are eligible for a clinical trial. Whether it is ‘1st line chemotherapy’ - which is treatment given on the first presentation of the disease, or ‘2nd line chemotherapy’ - which is treatment given to the patient if the 1st line fails, and so on. I go over the consent form with the patient; explain what the trial entails; the side effects of the medications, and the scheduling of the medications.
How has cancer treatment improved in the 20 years you have been at PMCC? We are making great advancements in our clinical trials with our patients, where their treatment is tailored to their disease site. When we see our patient tumour markers go down, and tumour shrinkage on their CT scan, we get excited. Our patients are living much longer lives. This IS exciting.
What inspires you? My patients inspire me. Enrolling in a clinical trial is not only helping the patient fight their particular cancer, but they are helping other patients as well. This inspires me.
How do you get relief? Going home to my children. By taking them to the park, hockey practice, gymnastics. They give me relief. When I look at them, I hope they do not have to lose family or friends to cancer. This inspires me to keep going.
Do you think we can Conquer Cancer in our Lifetime? We are making leaps and bounds in conquering cancer, and have the determination to Conquer Cancer in Our Lifetime, and so yes, I believe we can. Thank you Bernadette. Maggie Bras
Albiruni Razak – Staff Medical Oncologist BRAS Drug Development Program A great oncologist once said: cancer doctors are inspired by either, (i) the attraction to science or, (ii) the effect of an inspirational teacher, or (iii) the cancer patients themselves. In my case, I truly believe all three contribute equally to who I am today. At a young age, I was intrigued by what makes things work, (i.e. plenty of broken toys – in order to see what was on the inside), and in my early teens, it led me to working on interesting projects, such as: building a combustion engine carburetor, or building a carbide cannon, (this only happened during festivals, but this is a story for another time, perhaps). In many ways, my inquisitive nature has led me to a medical career, including that of drug development in oncology. There were many factors that led me into oncology and drug development, but a huge part of it was due to really awesome mentors. I have three great mentors. Dr. Liam Grogan, is an oncologist in Dublin, Ireland, who first got me interested in oncology. He is a great teacher, and makes you feel valued. He also taught me of the need to be simply more than a physician. I then undertook higher oncology training in Newcastle, England, under Dr. Hilary Calvert, best known for his role in the discovery and dosing of Carboplatin. He is the person who made drug development in cancer interesting for me. He is simply brilliant. He teaches in such a way, that you obtain many skill sets and knowledge base with ease. He explains things so well, that you never forget them. Under his guidance, I understood many of the basic principles for oncology drug development, which I routinely use today. Following this, I undertook a Fellowship at the Bras Drug Development Program at the Princess Margaret Cancer Centre, where I was mentored by Dr. Lillian Siu. When I arrived, I was amazed at the set-up, productivity, and cutting edge work being done in this institution. Under Dr. Siu, I have many excellent opportunities in oncology drug development, and beyond. I quickly came to the conclusion, that Princess Margaret is a great place to work, and is where I wish to be. Therefore, when an opportunity came around for me to be part of this amazing staff, I seized it with both hands! I am truly grateful to be working with such great colleagues, in a conducive and collegial environment. My interest in cancer is also at a personal level. I have several close family members who have succumbed, or are bravely fighting cancer at the moment. Their plight, along with many other cancer sufferers, are not lost on me. I am humbled to play a role in the pursuit of improving outcomes for cancer patients. I do miss my family back in sunny Malaysia, but to me, I now call Toronto my home.
Albiruni Razak MD Assistant Professor of Medicine, Staff Medical Oncologist, Bras Drug Development Program Princess Margaret Cancer Centre, University of Toronto
“THE ROAD OF LIFE CAN ONLY REVEAL ITSELF AS IT IS TRAVELED; EACH TURN IN THE ROAD REVEALS A SURPRISE. OUR FUTURE IS HIDDEN.” – ANONYMOUS
Greetings from Paul Alofs The BRAS Drug Development Program at Princess Margaret Cancer Centre is at the forefront of our Billion Dollar Challenge to create a new gold standard in cancer care, Personalized Cancer Medicine. To meet this challenge, The Princess Margaret is reaching out to our donor community to help us raise $500 million, which our researchers hope to match with $500 million in research grants. This new gold standard in cancer care will use the “genetic fingerprint” of each patient to find the right treatment for the right patient at the right time. The BRAS Program is dedicated to conducting early phase clinical trials involving patients with advanced cancer. This groundbreaking work has influenced the future of cancer care at The Princess Margaret, as much, or more than any other program begun in the past 10 years. That’s because its founders, Robert and Maggie Bras, understood the critical importance of studying the effectiveness of new drugs, to understand how they can be used to provide personalized cancer care. Robert was an entrepreneur with a generous heart, a father of six and grandfather of 12, who lost his brave battle with cancer in 2002, just 20 months after he and Maggie established the program. Doctors and scientists in the BRAS Program, have applied the genetic analysis funded by The Princess Margaret Cancer Foundation, to selectively test drug treatments based on the mutations evident in a patient’s cancer. Their global impact on cancer research – and the lives of people with cancer – has been recognized through continued successful peer reviews and grant funding. After ten years of hard work, the BRAS program has earned the credibility, and international reputation necessary, to be chosen by pharmaceutical companies and government agencies, to test the most promising new cancer drugs. The BRAS Program is now considered the world leader in innovative drug studies. Thanks to visionaries like the Bras family, and people like you, Princess Margaret Cancer Centre is now among the top 5 cancer research centres in the world. Together, we will conquer cancer in our lifetime. Once again, thank you for your generous support. Paul Alofs President & CEO The Princess Margaret Cancer Foundation
MISSION STATEMENT Exciting breakthroughs in the understanding of cancer biology continue to identify new approaches to cancer therapy. The goal of The Robert & Maggie Bras and Family New Drug Development Program at Princess Margaret Hospital is to identify new approaches to cancer therapy, for the treatment, management and eradication of this disease. ESTABLISHMENT The Princess Margaret Hospital Foundation (The â€œFoundationâ€?) hereby agrees to establish The Robert & Maggie Bras and Family New Drug Development Program Fund (the fund) PURPOSE The purpose of the Fund would be to aid in the creation of a collaborative resource environment devoted to research in new drug development.
August 29, 2002
In October of 2013, The Robert & Maggie Bras and Family New Drug Development Program undertook a rebranding, which meant developing a new look, a new name, and a new logo. After much discussion by Drs. Malcolm Moore, Lillian Siu, Amit Oza, Philippe Bedard, Albiruni Razak and Ms. Maggie Bras, our new name was chosen. We have now become the BRAS Drug Development Program. So we landed on a new name, and now we needed a new logo. We decided to launch a competition to design a logo which would clearly represent what the program embodies. All personnel from the BRAS Drug Development Program were invited to enter, and we received 20 high quality submissions from no less than 46 members of the BRAS DDP. And the winner was: Celeste Yu! Celeste Yu is the Program Manager of the Cancer Genomics Program. Please join me in congratulating Celeste for her wonderful contribution, and a big thank you to all those of the BRAS Drug Development Program who partook in this exciting initiative. Dr. Albiruni Razak, BRAS Drug Development Program Staff Medical Oncologist Princess Margaret Cancer Centre & Mount Sinai Hospital
â€œThe winning logo takes inspiration from the classic Ascent of Man diagram. The capsules demonstrate an abstracted form of a drug ascending in size representing the different phases of anti-cancer drug development. The intent was to create a logo that evoked a narrative of optimism and progress, while using a clean, modern aesthetic to emphasize the cutting-edge relevance of the BRAS Drug Development Programâ€?.
Celeste Yu, Program Manager, Cancer Genomics Program Princess Margaret Cancer Centre
We Would Like to Acknowledge These Exceptional Supporters of the Bras Drug Development Program…
Abraxis BioScience, Inc. Andrea Federer Anonymous Donors Anonymous Donor in support of: Pancreas Cancer Rapid Diagnosis & Research Alloway Trust Keith Ambachtsheer & Virginia Atkin Bayer Heathcare BMO Bank of Montreal BMO Harris Private Banking Boston Pizza International John & Susan Bowey Jamie & Leah Bras Jennifer Bras Robert & Maggie Bras Maggie Bras The Robert Bras & Family Charity Golf Tournament Anne-Marie Canning Ellen Clare Perry & Cathy Dolente Duviner Family Francis Family Gluckstein Design Planning Inc Goodmans LLP Charles Hanna The Hudson’s Bay Intact Insurance Carlos & Alexandra Jardino The Norman and Margaret Jewison Charitable Foundation
Elise Kalles In honor of Melissa Ann Katzman Fraser & Heather Latta David & Susan Leslie John & Esther Loewen Doug & Anne Lunau Arny & Carmen Kondrat Mantella Corporation Carmela McKay Merck Frosst Canada & Co. Malcolm Moore Paul & Holly Miklas The Muzzo Family The Agency Canada National Bank Financial Paul & Tracey Neziol E&G Odette Foundation Desmond & Pamela O’Rorke Panda Bears Walk Nancy Pencer Roche Rogers Edward & Suzanne Rogers Gerry & Caren Ruby Sage Investments Limited Schering Canada Inc. TD Financial Group The National Colorectal Campaign Trudell Medical Limited
Donations may be made through BrasDDP.com Charitiable Organization Number 88900 75797 RR0001 The Princess Margaret Cancer Foundation Special thanks to Cynthia Kinch, Editor and also to Doug Bell and the team at Copyright Copy Centre in Etobicoke, who donate their services in the publication of our printed materials. Helping Hand 7th Edition Published and Edited by Maggie Bras. Layout & Design courtesy of Jane Brass.