A Clinical Trial System for the Era of Precision Cancer Medicine
A Report from the National Cancer Institute
by Jeffrey Abrams, MD
The National Cancer Institute has the largest oncology clinical trials program in the world, supporting, fully or in part, 3,775 active clinical trials and enrolling more than 35,000 clinical trial participants annually. Yet, as a director of NCI-supported clinical trials, I know that behind every statistic is a person, each of whom brings his or her own motivations and hopes to the table when deciding whether to participate in a clinical trial.
For instance, Pamela, who was diagnosed with multiple myeloma, explains her decision to participate in a clinical trial this way: “This will be my chance to help give back and to help other people, maybe even my family, in the future.”
Clinical trials, which typically involve hundreds of volunteers like Pamela, are the final step in the often long, arduous process of determining whether new medications, tests, imaging techniques, and other treatment strategies are safe and effective. The U.S. Food and Drug Administration approves most cancer drugs only after a large clinical trial finds the drug to be capable of improving treatment outcomes, either by delaying tumor recurrence or prolonging survival compared to the standard treatment, assuming that the new treatment doesn’t produce serious side effects that outweigh the potential benefit of extended life.
NCI-supported clinical trials, which take place in research institutions and in communities across the country, have produced many important advances in cancer care over the past 50 years. For example, clinical trials have demonstrated the importance of using chemotherapy after surgery to improve survival in common cancers like colorectal and breast cancer, established new ways to manage treatment-related side effects like nausea and fatigue, and vastly improved survival for many children with cancer while reducing the short- and long-term side effects of treatment.
Many of the changes to NCI’s clinical trials programs are the result of nearly a decade of work, including exhaustive reviews by several groups of outside experts and recommendations from the Institute of Medicine.
However, even with a solid record of accomplishments, we know it is critical that the structures we support to conduct clinical trials keep pace with the latest advances in cancer research. The pre-clinical component of new drug development – that is, the research performed in the laboratory on cells and in animal models, for example – has shortened, and new drugs now move from the laboratory to the clinic with much greater speed than in the past. To take advantage of this, the clinical trial infrastructure must be nimble, efficient, and capable of screening large numbers of people to find those whose tumors are best suited to the new drug being tested. That’s why we are transforming NCI’s clinical trials system in a way that benefits researchers, the institutions that support and conduct the trials, and most importantly, people like Pamela, who rely on clinical trials for state-of-the-art treatments that may lead to better strategies for treating and managing cancer.
Responding to Complexity
Advances in medical technology and our understanding of cancer have changed the science of cancer research. To keep pace with those advances, and to accommodate the fiscal climate in which we live, NCI is adapting its clinical trials program to ensure that we serve the needs of the people who are relying on it.
Researchers can now dive deep into the machinery of cancer cells, as well as the normal cells and tissues that surround tumors, allowing them to dissect the communication pathways in tumor cells and catalog the molecular changes that allow tumor cells to evade chemotherapy, radiation, and attack by the immune system.
This evolution in our understanding of cancer means that we no longer think of cancer as a monolithic disease that behaves in a uniform fashion in every person who is diagnosed. We are increasingly describing and treating individuals’ diseases according to the genetic and biochemical changes that are driving it to grow and spread. We call this treatment approach precision medicine. It recognizes that each person’s cancer is unique, and that, as much as possible, treatment must be selected based upon the alterations seen in each tumor.
It’s our greater appreciation of the complexity of cancer, and the always present need to manage taxpayer dollars in the wisest, most judicious fashion, that necessitate the way we plan and conduct clinical trials.
Better Science, Better Results
This past March, NCI officially launched the National Clinical Trials Network (NCTN), a new clinical trials network that provides an infrastructure for NCI treatment, screening, and diagnostic trials. Later this year, NCI will launch the National Community Oncology Research Program (NCORP), a community-based program that complements the treatment trials of the NCTN but also emphasizes cancer control (trials aimed at reducing side effects from cancer or its treatment) and cancer prevention trials. NCORP will also study cancer-care delivery issues, studying how cancer care is actually delivered to people in their own communities by examining the impact of economic and behavioral issues affecting healthcare delivery. Both NCTN and NCORP are the products of the consolidation of existing clinical trials programs. Indeed, the predecessor to the NCTN, the Clinical Trials Cooperative Group Program, had remained essentially unchanged for more than five decades.
NCTN is devoted to conducting late-stage (phase II and III) clinical trials that test new treatments and new ways of incorporating advanced imaging technologies into treatment. Working in tandem with NCTN, NCORP will focus (although not exclusively) on trials that will test new ways of preventing cancer and improving the delivery of care, as well as studies that provide important information about the effectiveness of commonly used treatments.
The former nine adult Cooperative Groups (research teams, often from large academic medical centers, that work together on clinical trials) have consolidated to form four adult groups in NCTN, and, as was the case under the previous clinical trials system, an additional large group is focused solely on childhood cancers.
The NCTN launch features a number of other critical changes, including
- a new infrastructure to capture and manage the wealth of data from NCI-funded trials;
- a standardized process for reviewing and prioritizing proposals for new clinical trials, with an emphasis on supporting trials that are likely to most benefit patient care;
- a focus on speeding up the launch of trials and establishing a more rigorous process for ensuring that they stay on schedule and are completed as quickly as possible; and
- a unified, centralized system that ensures a more streamlined ethics review is possible while still insuring all the necessary safety precautions are in place for trial volunteers.
NCORP consolidated two community-based clinical research programs into a single entity. The new program ensures that people across the country, in communities large and small, have access to cutting-edge research and can be part of the movement toward precision medicine. The program’s operating approach will share the principles underlying the approach used in the NCTN.
We’re already seeing what the future of clinical trials looks like with the recent launch of Lung-MAP, the first of several NCTN precision medicine clinical trials. These trials will use the latest genomic technologies to identify the molecular drivers of individuals’ cancers and test whether new agents that target tumors with these molecular abnormalities are superior to standard treatments.
Upholding Our Commitment
Many of the changes to NCI’s clinical trials programs are the result of nearly a decade of work, including exhaustive reviews by several groups of outside experts and recommendations from the Institute of Medicine. Leading cancer researchers, experts in clinical trials, and patient advocates all played critical roles in formulating these changes.
Even with the extensive feedback and preparation that has gone into this transition, changes as substantial and important as these are never easy. We are working closely with the research community to manage the challenges, to answer the critical questions, and to ensure as smooth a transition as possible.
Throughout this process, we at NCI will make certain that the fundamental principles and values of clinical research are upheld. We remain committed to each person enrolled in a clinical trial and will ensure that they continue to have the opportunity to receive the full benefit of those trials.
The leadership at NCI is confident that this effort will succeed. The pace of scientific advances and the hundreds of thousands of people each year who depend on those advances demand nothing less.
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Since 1994, NCI has provided an exclusive report for Coping’s July/August Celebration Issue. Dr. Jeffrey Abrams is associate director of the Cancer Therapy Evaluation Program and acting director of Clinical Research in NCI’s Division of Cancer Treatment and Diagnosis.
If you’re interested in participating in a clinical trial, visit ClinicalTrials.gov to find a study near you.
This article was published in Coping® with Cancer magazine, July/August 2014.