Clinical trials are the final step before a new drug or treatment is approved for broad use in patients. In a series of phases, these trials investigate whether a new drug or treatment is safe, can be effectively administered and, of course, that it achieves its purpose of improving or curing a disease or medical condition.
Historically, clinical trials have taken a long time to conduct at a usually high cost. There are dozens of regulatory and investigatory hoops to jump through and, by design, most trials require large numbers of participants to draw even the smallest of conclusions. It's not uncommon for a new drug on the market to have involved thousands of participants in multi-million-dollar trials spanning a decade or more just to arrive at a remedy benefiting a sliver of patients in need.
It's a big reason why modern medical care is so expensive and often so frustrating. The system works (sort of), but there must be a better way.
In a recent issue of The Cancer Letter, a peer-reviewed medical journal, Ned Sharpless, M.D., the National Cancer Institute (NCI) director and my former counterpart at the Lineberger Comprehensive Cancer Center at the University of North Carolina , made similar points. Clinical trials were becoming bigger in size, but fewer in number. It was hard to find enough qualified participants to achieve even limited therapeutic progress.
But Sharpless was also hopeful. The shift to precision medicine — the idea of basing patient treatment on specific genetic, environmental and lifestyle factors — was beginning to change the way clinical trials are conducted.
Cancer research and treatment is leading the way. What happens in oncology won't stay in oncology. For example, a national trial called NCI-MATCH is an ambitious collaboration among cancer institutions, including Moores Cancer Center, to provide treatment to cancer patients based on genetic changes or mutations found in their tumors through advanced genomic sequencing and other tests. There are 18 treatment arms, each enrolling approximately 35 patients whose tumors have a specific genetic change. The drugs being used have either already been approved by the U.S. Food and Drug Administration for another type of cancer or they are still being tested in other clinical trials but have shown some effectiveness against tumors with a particular genetic change.
One big and persistent challenge has always been getting people to participate in trials. It's estimated only 3-5 percent of adult cancer patients enroll in a trial, despite the opportunity to receive cutting-edge therapies. Maybe that's not surprising. Many trials have restrictive eligibility requirements; it's difficult to qualify. Also, it can be hard to persuade someone to participate when the odds that the therapy will be individually effective might be quite small — and the person might actually receive a placebo.
Smaller trials involving only patients specifically identified as most likely to benefit from a targeted drug makes compelling sense. "By creating trials that are for the patients, as opposed to patients being there for the trials, we potentially help more patients, which leads to more accrual (of knowledge and know-how), which can then help more patients," said Sandip Patel, M.D., a medical oncologist at Moores.
Many doctors and researchers are keenly watching the NCI-MATCH trial to see how it works and how well. Some are pressing ahead with similar ideas. At Moores, for example, there are several like-minded trials already underway:
• The I-PREDICT trial, co-led by Jason Sicklick, M.D., a surgical oncologist, and Razelle Kurzrock, M.D., director of the Center for Personalized Cancer Therapy and Clinical Trials Office at Moores, conducts genomic testing on tumor tissues in patients with diverse types of cancer, then matches those findings to best therapies. Where there is no appropriate matched therapy, patients receive systemic chemotherapy according to their physician's discretion. The resulting information is used to determine whether patients respond better when their physicians choose treatment according to the genetic makeup of their tumor.
• The DART trial is co-led by principal investigators Kurzrock, Patel and Young Kwang Chae, M.D., at Northwestern University. It leverages the NCI-MATCH effort to specifically test a pair of promising immunotherapy drugs to help the immune system fight rare cancers, which despite the name account for more than 20 percent of cancers diagnosed worldwide.
• And the MyPathway trial, which recently published encouraging results with Kurzrock as senior author, looks for specific molecular alterations in tumors, using that information to guide selection of effective targeted treatment of patients with several types of cancer.
Change is inevitable, said Ezra Cohen, M.D., associate director for translational science who treats head and neck cancers at Moores. "The reality is that all patients are going to get some sort of next-generation sequencing in the next five years. This is not stoppable, and it will mean that other medical and cancer centers will begin to do we are already doing."
— Scott M. Lippman, M.D., is director of UCSD Moores Cancer Center. His column on medical advances from the front lines of cancer research and care appears in La Jolla Light each month. You can reach Dr. Lippman at email@example.com