The disgrace of cancer clinical trials
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A woman battling leukemia sat across from me the other day, eager to hear the news:

Would she qualify to be part of a clinical research trial? Or not?

Her quandary is far too common. Thousands of adult cancer patients with limited available treatment options are considered for clinical trials, but fewer than five percent are actually selected.


And that is a national disgrace. The 21st Century Cures Act, just signed into law by President Obama, supports the Vice President’s Cancer Moonshot, which identifies the low number  — less than five percent — of adult patients considered eligible for  cancer clinical research trials as one of the main  barriers to progress in the war against cancer. Compare this to the 60 percent of pediatric cancer patients who enroll in such studies. Why don’t adults appreciate the same imperative?

The fault lies not with our patients, but with those who design these studies. To maximize the likelihood of detecting clinically meaningful effects from the drugs being studied, trials seek fit, homogenous patient populations.

At first blush, this makes sense: investigators, and the Food and Drug Administration (FDA,) want to clearly define a drug’s safety and efficacy, and avoid erroneously attributing consequences of other medical conditions to the drug. It wouldn’t be fair, for example, in a patient with severe cardiac disease who experiences a heart attack while on a clinical trial, to say that this unfortunate event was unequivocally caused by a study drug.

As a consequence, many adults with cancer flunk the eligibility criteria that would allow them to join these trials, and the patients who are enrolled in these studies don’t truly reflect the U.S. population who will ultimately be treated by the approved drug.

Some in the field joke that a patient has to be an Olympic athlete to qualify for a study; but it’s no joke. Cancer clinical trial eligibility criteria are rigid — and recent research reveals that this is unnecessary.

As background, different drugs are processed through different organs. If, for example, the fictitious “drugTumorkillamab” was processed through the liver, or caused liver inflammation, it might make sense that patients with liver abnormalities should not enroll to a trial of that drug. Patients with heart or kidney problems should still be eligible, though, because the drug is not metabolized through those organs. Unfortunately, this doesn’t happen. 

In a study we conducted that was published this month in the journal Leukemia, we examined 97 recent randomized trials conducted in cancers of the blood and bone marrow, and involving almost 44,000 patients, to uncover whether the eligibility criteria reflected the known metabolism or toxicities of the drugs being studied.  

We found that almost 90 percent of the trials had eligibility criteria that excluded patients with compromised heart, kidney, or liver function — but with no correlation to the established metabolism or safety profiles of the drugs being tested. In other words, patients were unnecessarily turned away from potentially life-altering treatments. At best, the eligibility criteria appeared to recruit only the healthiest cancer patients to these trials; and at worst, given their similarities from one study to the next, the criteria appeared to be a cut-and-paste job.

These findings begged the question: What would happen to patients who were supposed to be ineligible for these clinical trials, if they were treated on them anyway? 

In a subsequent study we presented at the American Society of Hematology annual meeting this month, we analyzed 13 leukemia trials conducted through the National Cancer Institute’s Southwest Oncology Group between 2005-2015.Each included patients who didn’t actually meet the stringent entry criteria, but whose ineligibility wasn’t discovered until the studies had been completed. 

What we found was that these “ineligible” patients were just as likely to go into remission of their leukemia, and to live just as long, as eligible patients. As in our previous study, the eligibility criteria appeared to be needlessly restrictive.  Further evidence that the bar is set too high for patients seeking enrollment in clinical trials.

Another recent study, conducted at the MD Anderson Cancer Center, took the notion of liberalizing cancer trial eligibility criteria to its extreme. In what sounds like a choice for contestants on the television show Let’s Make a Deal, investigators offered patients who would otherwise be considered ineligible for standard clinical trials for bone marrow cancer one more option: a trial whose eligibility criteria were actually the ineligibility criteria of the other trials.  

The results of this trial, which included only imperfect candidates? Their cancers improved at the same rates, and they experienced comparable toxicities, to patients with normal organ function enrolled in other similar trials. 

The goals of improving cancer trial conduct and efficiency are long in coming and crucial if we are to advance cancer care rapidly. But without broadening access to studies for people with other medical conditions, they only rarely be available to the cancer patient who actually sits a couple of feet from us in our exam rooms.

As for my leukemia patient, I had to deliver the bad news: She was ineligible for the trial because her liver tests were slightly outside the range specified in the study. 

“What’s next for me?” she asked.

I didn’t have a quick answer.

Mikkael A. Sekeres, MD, MS is the director, leukemia program and the vice-chair for clinical research at Cleveland Clinic Cancer Institute. Sekeres is a former chair of oncologic Drugs Advisory Committee, FDA. You can find him on Twitter at @MikkaelSekeres.

The views expressed by contributors are their own and not the views of The Hill.