LYNN CLARK
ST RY inside
Sav i n g J o e l G r o e b n e r People who go on phase I cancer clinical trials are pioneers. They have almost always exhausted all other standard therapies. And they enroll in the trial with eyes open and no guarantees. By participating, they help scientists gather information that may help future patients because, unfortunately, most people on phase I clinical trials do not survive as long as Joel. The average life expectancy for someone with metastatic melanoma is months, not years, and certainly not decades. Ask Joel about the broader purpose for his participation in a clinical trial, and he’ll be blunt. “It’s fantastic that they’ve found something that will work for others, but in the beginning, I was not thinking about the greater good. All I cared about was saving Joel Groebner.” Julie Banahan, an oncology nurse, has been on Joel’s care team for a decade. “He is the definition of Superman,” she says. “His attitude is inspiring. He has great karma. You just feel it.” Lia Gore, MD, who took over Joel’s care when Holden moved on, says, “Joel is defying the odds. He’s at the intersection of science and technology and a few lucky guesses. Who ever thought that he’d live to see his kid go to kindergarten? He’s a vibrant, contributing member to our society.” Make a donation to support cancer clinical trials at the CU Cancer Center at www.coloradocancerblogs.org/give.
Phase I Clinical Trials put cancer patients on the cutting edge Patients like Joel Groebner (page 12) and Ellen Smith (page 4) are examples of people living at the cutting edge of medical science. Both are taking “experimental” cancer drugs, and the therapies are keeping their diseases in check.
Above: Lia Gore, MD, here with Joel and Scott Holden, says Joel is defying the odds.
Nicole Kofoed
and therefore choose not to take blood transfusions, finding an appropriate trial wasn’t easy. “We’ve always looked for what new treatments might be available,” Danette says. “We scoured the country for a trial, as did Dr. Holden. Because we didn’t want the blood transfusion, it was disqualified, disqualified, disqualified.” In August 2001, Holden called and said, “I think I have something for you.” Melanoma tumors are highly reliant on blood vessels to deliver the energy they need to grow and spread. The experimental drug PI-88, manufactured by Progen Pharmaceuticals, inhibits blood vessel formation by targeting a VEGF protein, cutting off its function and therefore starving the tumor. As Joel started his first treatment week of PI-88, he and Danette understood it was not likely to work, but they believed doing something was better than nothing. The next month, Joel, Danette and 3-year-old Em traveled to Minnesota for a family reunion. Danette remembers it as awful. “Everybody knew what was going on—that we were there to say goodbye,” she recalls. “But no one said goodbye.” Joel remembers it as a beautiful time of year. “Joel’s always been a glass-half-full guy,” his wife says, laughing. “His amazing spirit is what has gotten him through this.” After just two cycles of four bi-weekly PI-88 shots, Joel’s tumors shrunk by half, and then by half again during the next three years. His disease has been stable since.
Right: PI-88.
Joel says he’s been motivated to fight his disease by the desire to have Em remember him. The couple learned that long-term memory kicks in around age 4 or 5. “We weren’t thinking about 10 years,” Danette says. “We just wanted Em to remember her dad.” “Now I just want to survive her adolescence,” Joel jokes. The Groebners say living with Joel’s illness for their entire marriage has taught them, “You can be happy in the most awful circumstances.” “Your priorities change,” Danette says. “We find ourselves asking, ‘Is this worth arguing over?’ ” Today, Joel is more concerned with developing a secondary cancer from radiation exposure he’s had over the years from CT scans than dying from melanoma. He jokes about worrying about his weight and cholesterol—health concerns the average advanced cancer patient doesn’t have. He says he is grateful for the experimental drug that Holden found for him, which has allowed Em not only to remember him, but to know him. He’s grateful for the extraordinary team at the CU Cancer Center who have supported him and become his friends. He is grateful for his health insurance, saying, “I must be the $6 million man by now”—referring to the cost of his treatment to date. Most of all, he is grateful for his wife, and for his daughter, and for his life. “Some people get cancer and say, ‘I’m done,’” he says. “I don’t get it. If this stops working, I know I have other options. I don’t care what kind of treatment comes next. I have to do something. I can’t give up. I have too much to live for.”
Cancer clinical trials—the highly regulated and monitored system that tests new drugs, new combinations of drugs and other treatments that are not approved for use by the Food and Drug Administration—are part of standard care at academic cancer centers like the University of Colorado Cancer Center. Today, nearly every patient at the center’s lead care partners— University of Colorado Hospital and Children’s Hospital Colorado—are evaluated to see if can be offered the option of a clinical trial. Evaluation often includes testing each patient’s tumor to see if the genes, proteins or other biologic factors the experimental drug targets are present. Patients are also evaluated for a host of other factors, including their general health status and the treatments they’ve been on before. Not all cancer patients are on a phase I clinical trial. In fact, those trials are usually reserved for patients for whom standard treatments have failed. The experimental drug may be their best remaining chance for a response.
F i r st i n M a n New therapies are tested extensively in animal models to see if they work—kill cancer in the way they are designed to—before they are brought to people. Often the drugs are created by pharmaceutical companies, and the companies come to academic cancer centers to “translate” the successful lab discoveries into human patients via a phase I clinical trial.
These so-called first in man trials aren’t looking for whether the drug kills the cancer. Instead, the goal is to determine how it behaves in a human. The clinical trialists—physicians and nurses trained to specifically conduct clinical trials—are looking for dose-limiting toxicities to characterize the body’s general tolerance of the agent. The first group of patients gets the lowest dose, and then the amount of the drug or frequency is increased until patients get intolerable side effects. When that dosage is determined, the drug can move on to phase II testing, where further efficacy testing comes into play. Sometimes, a small percentage of patients will see their tumors shrink or disappear with an experimental agent. In the past, when trial data was collected on paper and analyzed months after all patients had completed the protocol, these patients were often overlooked. But today, data goes back to the trial sponsors within days or even hours of the patient visit thanks to electronic medical records and databases. Real-time access to what’s happening in that patient allows doctors to notice trends when they can be taken advantage of. Time is money, and time is life for these patients. If a small number of patients respond to the drug, clinical researchers can usually figure out what the commonalities are and open a secondary arm of the trial that enrolls only patients with those features. That’s what happened with crizotinib and patients with the ALK fusion protein in lung cancer, and as a result, the drug is now approved by the FDA for treating those patients just three years after it entered phase I trials. —Lynn Clark
Can c e r tr ials vs oth e r tr ials All drugs, regardless of disease, have to be extensively and carefully tested before the FDA will approve them for regular use in humans. But cancer clinical trials are different from the trials you might hear advertised on the radio. Here’s how, using phase I trials as the example. Phase I Cancer Trial
other Phase I Trial
Only cancer patients can enroll
Normal population can enroll
Patients with limited treatment options
Patients aren’t being treated for a particular disease
Patients do not receive monetary compensation
Patients often receive monetary compensation
Standard care procedures are billed to insurance or the patient
There is no standard care to compare the new drug to
All study treatments and procedures are covered
All costs are covered by the trial
Patients undergo extensive monitoring
Patients undergo extensive monitoring
Goal is to determine correct dosing schedule and toxicity
Goal is to determine levels of toxicity
Also looking at specific characteristics of this patient and this tumor
Not targeted
To search for a cancer clinical trial, visit www.uch.edu/conditions/cancer/research/research_trials/
14 www.coloradocancercenter.org
15 C3: Winter 2011