1. DiGiulio, Sarah

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Cancer therapies and cancer care are more advanced today than ever before. And cancer researchers are continuously learning how to grow what we know. But to do that effectively, two thought leaders in cancer research say the clinical trial process that validates new treatments and delivery of care needs a revamp.

Norman Sharpless, MD... - Click to enlarge in new windowNorman Sharpless, MD. Norman Sharpless, MD

Norman Sharpless, MD, and James H. Doroshow, MD, coauthored a Viewpoint editorial that was published earlier this year in JAMA highlighting the different ways they suggest cancer clinical trials need to be modernized (2019;321:447-448). At that time, Sharpless was Director of the NCI; in April, he became acting Commissioner of the FDA. Doroshow is NCI's Director of the Division of Cancer Treatment and Diagnosis.


"The approaches we laid out are designed to reduce the financial pressure of clinical trials, conduct trials that complement those of industry, facilitate access to investigational agents, base trials on molecular alterations, and improve accrual rates," Sharpless told Oncology Times.


"Rethinking clinical trials is also about finding ways to overcome barriers that can get in the way of executing the most efficient trials," he noted. Here's what else Sharpless shared about the potential future of cancer clinical trials.


1 What prompted you and Dr. Doroshow to write this JAMA Viewpoint article now?

"With so many new and promising cancer treatments being developed, the importance of clinical trials to test them has never been more important. The past 10 years, in particular, have seen a transformational reworking of the NCI's clinical trials infrastructure.


"Clinical trials are the fundamental means for making progress in cancer treatment and prevention, but we need a shift in how we think about and design clinical trials to make them work better for researchers, clinicians, and patients.


"These changes must address such challenges as cancer heterogeneity, poor accrual rates, the difficulty patients have in finding trials, unnecessary exclusion criteria, and onerous costs. In short, we need to modernize clinical trials, moving towards smaller, more focused, more rapid trials that can often be deployed in a community setting."


2 The editorial talks about "right-sizing" trials as a way to drive down costs. What does it mean to "right-size" a clinical trial?

"'Right-sizing' clinical trials involves looking at the efficiency of trials, including decreasing the number of patients required to test the treatment under investigation. For example, as we say in the article, with some trials of highly active agents, it may be possible to forgo traditional control group interventions in favor of well-annotated 'synthetic' control arms that are created with data from previous trials.


"NCI is also exploring the use of novel endpoints that reflect the mechanism of action of the drug under study through pragmatic trials that are conducted in clinical practice settings, and through augmented annotation and aggregation of new and existing trials data. Such approaches would make it possible to answer relevant clinical questions without additional enrollment.


"Having said that, I am certain the NCI will need to continue to support large randomized trials of certain types of clinical questions. Such trials are sometimes the only appropriate way to answer certain key questions related to oncologic clinical practice. A recent NCI-sponsored example of such a trial is the TAILORx trial, which evaluated therapeutic de-escalation in women with estrogen receptor-positive breast cancer. The key for the NCI is to figure out the smallest appropriate trial design needed to address the clinical question being addressed."


3 You also talk about improving clinical trial accrual rates. What efforts are currently being made at NCI to do this? What will actually push the needle on changing this issue?

"One of our most promising efforts to improve accrual rates among our underserved populations is the NCI Community Oncology Research Program (NCORP) that brings cancer clinical trials to community settings. NCORP also allows us to reach more minority and underserved persons in the communities where they live. NCORP gives patients access to trials they might not otherwise have access to.


"The program not only increases the generalizability of study findings, but also illuminates potential disparities in outcomes. The NCI-MATCH trial, for example, is available at 1,100 sites across the country through NCI's National Clinical Trials Network and NCORP, leading to enrollment that better reflects the overall patient population.


"Maximizing accrual rates to clinical trials while still ensuring patient safety is a priority for NCI. For more than a decade, NCI has been committed to expanding the eligibility criteria for NCI-funded clinical trials, including decreasing the use of upper age limits in adult trials and making it possible for cancer patients who are also HIV-positive to participate in more trials.


"We've also revised our clinical trial protocol template to ensure participation by certain patients with brain metastasis and patients with altered organ function. The goal is to ensure that the results of clinical trials are broadly generalizable, so that as many patients as possible can benefit from new targeted cancer treatments and immunotherapies."