Editor's note: This is the first of a two-part package shedding light on cancer clinical trials. Here, you'll meet a patient in a trial. Part two helps separate the facts from fiction regarding clinical studies.
Wendy Ramsey describes herself as the kind of person who likes to dig into a problem, come up with a plan and run with it. So when her doctor phoned with a diagnosis that finally explained her prolonged fatigue, it’s perhaps no surprise that the first thing she did was turn on her computer. Only after she’d read up on the disease did she walk into the next room and tell her husband she had leukemia.
Today, Ramsey, 58, is enrolled in a clinical trial through Fred Hutchinson Cancer Research Center to test a new treatment. She is in rare company. Nationwide, just 3 to 5 percent of adult cancer patients take part in treatment trials, a rate that has not budged in years. Yet clinical trials are the only accepted scientific method to test if a new treatment is safe and effective in humans.
Why do the vast majority of adult cancer patients not take part in clinical trials? Or, put another way, why do people like Ramsey agree to do them?
Ramsey’s participation may be due at least in part to her own inquisitive, pro-active nature. But she also said that she is “incredibly, incredibly grateful” for the information she got from online support groups as well as from her doctors, whom she described as “nothing short of remarkable.” One of the main reasons more people don’t enroll in trials, experts say, is because their doctors don’t inform them of this option.
Ramsey, who lives in Spokane, also counts herself lucky to have health insurance and the financial resources to handle the often hidden costs of participating in trials, including travel. Having to travel from a city without a major cancer research center or lacking good health insurance or other resources can often be an obstacle to participating in trials even when there is no charge for the actual drug being tested.
A third explanation for her participation is perhaps the starkest: Nothing else she tried worked.
“For some number of patients, a substantial percent, standard of care is working for them. Their disease is under control. They can live a reasonable life. They’re not really motivated to find some alternative treatment,” said Lori Jarrett, a clinical trial manager for Fred Hutch's Clinical Research Division. “The people who are looking at clinical trials are ones where standard of care has already been tried and it was either a very unpleasant experience or it didn’t work or didn’t have a lasting effect.”
Ramsey started out in the first group. She quickly found herself in the latter.
Like many people who experience baffling symptoms over a long period of time, Ramsey was almost relieved when she got her diagnosis in 2003 at age 47: At least she wasn’t losing her mind. She had been feeling exhausted for two years. At first she thought it was just due to the busy mechanical contracting business she ran with her husband, but nothing she tried—more exercise, less exercise, more protein, less—helped. “I’d thought, ‘You’re working full time, you’ve got two kids, you’re perimenopausal. Guess what? You’re tired,’” Ramsey said. “But it got to the point where I couldn’t do my job. There was something going on.”
At first, she appeared to have a form of leukemia that would progress slowly, if at all. Her Spokane oncologist advised watching and waiting.
Even during the watch-and-wait period, Ramsey spent a lot of time online. She came to trust one site in particular, started by a retired chemist whose late husband had had the same type of leukemia.
By the end of a year, Ramsey’s disease started to take off. Her strategy, influenced by her online research, was to avoid harsh chemotherapy while buying time for medical research to come up with new options. She opted for a targeted antibody therapy that, although not experimental, was not considered the standard treatment.
She also went to the Mayo Clinic in Rochester, Minnesota, where she obtained a detailed profile of her cancer. It was there that she enrolled in her first research study, although not one that tested new treatments. She, her parents and her then-teenage sons had their blood drawn for a study on what role heredity may play in the disease.
After a second round of targeted antibody therapy stopped working, she began to consider clinical treatment trials.
Her first trial was a Hutch study at Seattle Cancer Care Alliance, but she had to drop out because of the drug’s side effects. Next she enrolled in a clinical trial at the University of California San Diego. That treatment held the cancer at bay for about 15 months.
By this time, she had assembled an informal “board” of oncologists and researchers whom she trusted. It included her local oncologist in Spokane, researcher-physicians at Hutch/SCCA and a UC San Diego oncologist. She agreed to try chemotherapy after Dr. John Pagel of the Hutch and SCCA recommended it and her UC San Diego doctor agreed.
Some people get 12 years out of chemo. She got 12 months. Then the disease roared back.
“It became clear to me that when my disease starts to come back, it gains speed. It says: ‘I’m back, and I’m coming on strong,’” Ramsey said. “By now I’ve got a pretty good idea that, with each treatment I have less and less time to make a decision.”
It was at that point that she decided to take part in a Phase 1 trial.
Understanding phases of trials
Human cancer treatment trials are typically divided into three phases. Phase 1 clinical trials test a new experimental drug or intervention in a small number of people (around 20 to 80) to determine a safe dosage and identify side effects. In Phase 2, investigators give the drug to a larger number of patients, continuing to monitor its safety as they assess whether the agent works. Most experimental drugs fail before they make it to Phase 3, which tests for both safety and efficacy in hundreds or thousands of patients by comparing the outcomes between those taking the new drug and those getting standard care. To approve a new therapy, the federal Food and Drug Administration generally requires that it go through two Phase 3 trials.
Ramsey’s earlier trials had been Phase 2 trials, in which safety had already been determined. But by now, she felt that her only other option was a bone marrow transplant, a procedure pioneered clinically at Fred Hutch. Although the Hutch program at SCCA is one of the leading transplant centers in the nation, the treatment is lengthy, technically difficult, and carries risks of short- and long-term complications. So when Pagel told her about a Phase 1 trial and her San Diego oncologist gave her the same information, she decided to give it a try. (So as not to compromise the ongoing trial she is in, Fred Hutch is not able to publicly disclose the name of the drug being tested for her specific type of leukemia.)
“Honestly, in my opinion, you do not do a Phase 1 trial unless you’re out of options,” she said.
For the first month on the new medication — an oral pill taken once a day — she stayed in Seattle so that her reaction could be closely monitored. She and her husband rented a house, which was less expensive than staying in a hotel. After that, she returned twice a month to have her blood drawn. Trial protocols required that it be done at the lab sponsoring the study, not in Spokane. Over time, as she did well on the medication, the trips to Seattle to have her blood drawn dropped to once a month, then every two months, then — recently — every three.
Two years later — longer than any other therapy has worked — Ramsey’s cancer is barely detectable.
She describes her experience with the hard-earned caution of a cancer veteran, one who doesn’t want to over-promise what trials can deliver. The treatment, which still must go through Phase 2 and 3 trials, may turn out to help a certain percentage of people, she said. And right now, it looks like she may be in that group.
Even such guarded optimism brought her near tears.
“When you have cancer, there’s a little bit of you that waits for the next shoe to drop,” she said. “I get that many clinical trials are not successful. But the progress that has been made since I was diagnosed in 2003, just specifically in my disease, is off the charts. It provides so much hope. I think trials provide hope.”
As grateful as she is that the experimental drug is working for her so far, Ramsey is clear that participating in a trial was never just about her. As a mother of two adult sons, she is very aware that her disease tends to strike more males than females and that it clusters in families.
Clinical trials hold out hope not just for today’s patients but for future ones. “For me specifically,” she said, “that’s my boys.”
Mary Engel is a former staff writer at Fred Hutchinson Cancer Research Center. Previously, she covered medicine and health policy for the Los Angeles Times, where she was part of a team that won a Pulitzer Prize for Public Service. She was also a fellow at the Knight Science Journalism Program at MIT. Follow her on Twitter @Engel140.