Basket Trials: CROs and the changing face of clinical trials

September 7, 2016

By Angela Woodall, Healthcare and Environmental Reporter.

In 2015, Memorial Sloan Kettering, one of the nation’s most respected cancer treatment centers, set off a wave of excitement about clinical trials.

Researchers testing a drug called vemurafenib (aka Zelboraf) found that a therapy used to treat one kind of cancer could work for others. The findings, published in the New England Journal of Medicine, were remarkable enough.

But what set the study apart was something else. It marked the first published report from a “basket trial,” a new approach that combines precision medicine with clinical trial design.

“This is really a new breed of study,” said David Hyman, a cancer specialist at Memorial Sloan Kettering, who directed the research.

It’s also a really new breed of opportunity for contract research organizations.

CROs are, in the words of Association of Clinical Research Organizations spokesman John Lewis, “uniquely situated.”

Unpacking the Basket

The label basket trial comes from the practice of pooling oncology study participants with similar genetic mutations together instead of slotting them into trials based on specific cancers – one for lung cancer, another one to treat breast cancer, another for colon cancer and so on.

The approach seemed to come out of the blue. But in reality they were the extension of breakthroughs in DNA sequencing.

The American Association for Cancer Research summed up the context this way:

Decades of research have shown that there are more than 200 separate types and subtypes of cancer and that, even within the same type or subtype of cancer, there may be considerable variability at the genetic and molecular levels.

Armed with this information, investigators are developing drugs that attack cancers by honing in directly on the genetic and molecular abnormalities that drive them. To test these drugs efficiently, researchers are exploring novel approaches to designing clinical trials.

As an article in the Scientific American put it, basket trials were a “part of a wave of efforts to reform the costly and time-consuming process of drug approval that often fails to take into account the complex realities of cancer biology.”

The advantage to sponsors is obvious. Pool participants, lower costs and, ideally, produce results faster. In the end, patients benefit if tested drugs and devices get to them faster. Getting drugs to patients sooner explains why the FDA, an agency not known to shift gears easily, has begun to accept experimental strategies like basket trials.

But would pooling participants and streamlining trials mean less work for CROs?

“This is What CROs Do”

That’s a possible scenario but not a likely one, said Lewis, the Association of Clinical Research Organization’s senior vice president of policy and public affairs.

For one thing, basket trials only sound easy.

The challenges in designing a basket trial and interpreting the data generated by the trial are multiple, according to the physicians Amanda Redig, an internist, and Pasi Jänne, an oncologist. For one, they require writing 20 or more protocols—one for each cohort—and creating a screening and treatment infrastructure.

And, as they wrote, “rigorous evaluation of preclinical data when designing a basket study will continue to be of central importance.”

Those are challenges CROs deal with already and the same strengths that benefit sponsors in traditional trials give CROs an advantage in this new version, Lewis said.

CROs are a neutral partly with extensive project management experience across multiple sponsors, sites and trial arms, Lewis said. So they already have experience working with more than one sponsor at a time. They also know how to shift gears quickly, which is important because basket trials are nimble — they are looking across genetic mutations instead of locations so one arm of a trial can be shut down if another looks more promising.

“This is what CROs do,” Lewis said.

The next step is testing out much of the excitement basket trials generated is hype and how much is real.

Several trials are underway including the American Society for Clinical Oncology’s TAPUR trial, which will examine biomarker-directed off-label use of 13 drugs from five sponsors.

The National Cancer Institute is launching the basket NCI-MATCH study, which it describes as the “largest, most rigorous precision oncology trial in history.” NCI-MATCH aims to screen 3,000 patients with the goal of enrolling 1,000 across 20-25 molecularly defined subgroups.

Even if basket trials don’t revolutionize the landscape they will alter it for the better, said Jose Baselga, physician in chief at Sloan Kettering who helped pioneer the use of basket trial. “The rules of engagement have changed,” he said.

Angela Woodall, Healthcare and Environmental Reporter.

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