Since I was diagnosed with metastatic breast cancer a year and a half ago, I have been on four clinical trials. In fact, the only treatment I’ve had that hasn’t been trial based is the one I’m on now, an oral chemotherapy called Xeloda. Although I’ve had mixed success personally with trials, I’m a big fan of them and encourage anyone with a challenging disease like cancer, heart disease, Parkinson’s, Alzheimer’s, or others, to check out what’s available on https://clinicaltrials.gov and to ask your doctor.
What is a clinical trial? Clinical trials study both drugs and other modalities to determine safety and efficacy in humans, and whether or not a particular treatment is superior to what may already be on the market and approved by the relevant government agency (in the case of the U.S., that’s the FDA). Trials may be for healthy people or for those with a particular disease. For metastatic breast cancer, for example, there are currently more than 700 trials around the world studying various therapies. Some of these are particular to breast cancer, but increasingly, trials are open to more than one kind of cancer, sometimes termed “basket studies.” This is because a particular mutation may occur in more than one type of cancer, and a targeted therapy could address it.
Trials come, generally, in three phases (a fourth phase is sometimes added after a therapy is commercially available). Phase I is the most experimental as a drug, for example, has not yet been studied in humans. Phase I trials involve a fairly small number of people; different participants will be given different dosages to measure safety, side effects, and efficacy, as well as how a drug is absorbed in the system. Gradually, this process is refined, and a more mature Phase I trial—I’ve been on two of these—has more participants, although the administration may still vary according to which “arm” of the trial you are in. Phase II is an expansion of Phase I, where even more participants are enrolled. Finally, Phase III compares the study protocol or drug to an established alternative. In Phase III, you are randomized either to the standard protocol or the new alternative.
My first trial was a Phase III trial at Dartmouth, and I was randomized to the study drug, a marine based chemotherapy developed in Japan, called eribulin. This lasted about 5 months before the cancer began growing again, and I was removed from the trial. My second trial was a genomic test, administered out of Ohio State’s James Cancer Center, that identified mutations in my cancer that might be receptive to therapies. (The advantage of this trial was that the test was free, whereas having it done commercially would have been several thousand dollars, probably not reimbursed at that time by insurance.) My third and fourth trials were at Mass General, and both involved a combination of new, not yet on the market targeted drugs, and others that had shown efficacy. Unfortunately, none of these worked for long in my case (my doctor said they have all “underperformed” relative to expectations), but I have some comfort in knowing that my participation is advancing understanding of new therapies for other patients.
There are advantages and disadvantages to trials. The main advantage is that you are often (with the exception of Phase III trials when you are randomized to a standard therapy), getting the latest available scientific thinking—you have access to therapies that otherwise are not yet available. A second advantage is that you get very personalized treatment—trial nurses are assigned to each participant, and I have found them, without exception, fantastic to deal with and very proactive.
There are disadvantages, however. One is time. Often, especially in the earlier phases, you will be subjected to numerous blood draws and tests to determine how the drug is being absorbed (the record for me was 16 vials), sometimes with fasting and sometimes not. As you progress in the trial, these interventions become less frequent, but the schedule of treatment is often quite strict—on the Japanese-sponsored trial I was on, I had to cancel a planned international trip because it fell during a week I was scheduled for treatment, and the only exception allowed was if I had had a medical reason (e.g. low white blood cell counts). Secondly, trials can be quite strict on who they admit. This includes thresholds on certain blood levels, such as liver enzymes, white cell counts, and even mineral levels such as calcium, phosphorus, and potassium, as well as previous therapies (there is often a limit, for example, on the number of previous chemotherapies that you can have to be a participant in certain trials). In my case, now that I have brain metastases, a number of trials for which I would otherwise be eligible are off limits as many therapies do not cross the blood-brain barrier. Guidelines for continuing are also strict–the last trial I was on worked on some of my cancer, but I had a new lesion in my liver, so had to be removed from the trial as any new lesion is generally disqualifying. Finally, I’ve found that as a patient, you have to do a fair amount of your own research, as institutions generally are aware of and promote only their own trials. Research is how I found the genomic testing at the James Cancer Center, for example.
I am lucky in that I am near some world premier institutions, all NCI designated cancer centers, including Dartmouth and Mass General, where I’ve had treatment, as well as Dana Farber (and Memorial Sloan Kettering is not that far). These research hospitals tend to be where the bulk of trials take place, but smaller centers get in on the action as well, especially for Phase III trials. Having said this, many trials fail to enroll enough participants, and part of the reason for this is knowledge and access—I think some may fear they are being used as human lab rats– but also the complexity of participation. Despite the fact that I’ve already been on trials and the future options may be more limited, I remain committed to participation both for its potential benefits for me personally, and to advance the cause of better treatment for others.