Clinical Trial Versus Standard Protocol: Why and How to Enroll in a Trial


My job at Cancer Commons is to help cancer patients better understand and make decisions about their treatment. Through our Ask Cancer Commons service, I also strive to inform patients about new drugs in trials that they can discuss with their oncologists. Sometimes, I explain the rationale behind a patient’s current or upcoming treatment, and sometimes I try to convince patients to actually get treated, rather than hope that a vegetarian diet and herbal supplements will cure their metastatic disease.

However, I spend most of my time trying to match cancer patients with clinical trials. I consider this to be the most important service I can provide. I try to find trials that are suitable geographically, have the best treatment rationale, and are likely to accept the patient I am helping based on their personal health and treatment history. In this post, I share some of my thoughts about clinical trial enrollment and why it is so important for patients to consider getting treated through a trial.

The reason I promote trial participation is simple: the rate of new drug development and approval today is much higher than it was even three years ago. With more and more targeted drugs, immune system-directed treatments, cell-based therapy, and entirely new drug classes, the chances of getting the best treatment in a clinical trial are very high. The alternative, which is far more common, is protocol-guided treatment. This route takes you through the list of approved chemotherapy regimens as one after another stops working, with full awareness of the fact that the more lines of treatment behind you, the lower the expected benefit.

You may ask, why not rely on the treating oncologist to recommend a trial—the best trial—for the patient? Well, the answer is, again, simple: many oncologists simply do not have the time or inclination to learn about trials that are ongoing 100 or 1000 miles away. Most oncologists may know only about trials at the clinic in which they work (assuming that they do work in a clinical center that actually conducts trials, which most oncologists don’t). And the other sad fact is that few oncologists in community clinics have time to provide suggestions for trials. The burden is on patients, and I am trying to relieve it.

The problem is that enrollment in a trial is far from easy, and the process can be really frustrating. Some problems arise from the fact that clinicaltrials.gov—the major website that lists information about specific trials—is not particularly good at updating the status of each trial in a timely manner. Eligibility and exclusion criteria are often not clear or not complete. Trial enrollment categories may change without being reflected on the trial website. Should I even mention the simple fact that, often, the phone numbers and email addresses listed on each trial site do not provide an efficient communications channel?

Trial PI
A tip to ease trial enrollment: 1) Find the trial on clinicaltrials.gov. 2) Scroll down to “Contacts and Locations” and find the name of the trial investigator (not the main contact). 3) Make an appointment with the trial investigator, as you would do to receive a second opinion.

 

I have a suggestion on how to try and take at least some of the pain out of enrollment: get the name of the trial investigator (see image above). Sometimes it will appear on the specific trial page on clinicaltrials.gov, sometimes not. If not, search for trials on the website of the clinical center where the trial is being conducted, where the investigator’s name is always shown. Make an appointment with the trial investigator, as you would do to receive a second opinion. This doctor, who is really interested in enrolling patients quickly into the trial(s) she or he runs, will make a well-informed decision of whether you are a good candidate for a trial, and will facilitate your enrollment.

Let me give an example of an increasingly common issue that illustrates why it is better to be treated in a trial. You may have heard of immune checkpoint inhibitor drugs, which are relatively new, and some of which have been approved as second-line therapy. Nowadays, if your cancer (melanoma, lung, or kidney) has stopped responding to chemotherapy or a targeted drug, it is quite likely that your oncologist will prescribe nivolumab (Opdivo) or pembrolizumab (Keytruda; both are PD-1 blockers). This is the new, approved, standard protocol.

The truth is that while PD-1 blockers are great drugs, they only benefit around 20% to 30% of patients when given alone. This is still better than chemotherapy, of course. However, there are literally hundreds of trials that explore combinations of PD-1 and PD-L1 blockers with other treatments. Preliminary results show that the efficacy of PD-1/PD-L1 inhibitors in certain cancers could be bumped up twofold or more when they are given alongside chemotherapy, a targeted drug, or radiation.

Is it reasonable to wait, possibly for years, for the approval of these highly effective combinations so they will be become part of the standard protocol? Wouldn’t you jump on the opportunity to receive a combination treatment if there was a good chance that it would greatly increase your chances of response? Well, guess who is more likely to give you this opportunity: your protocol-guided oncologist, or one who is involved in trials and has a less orthodox approach to treatment?

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If you have specific questions about clinical trial enrollment for yourself or for a loved one, Ask Cancer Commons today.