A Clinical Trial System for the Era of Precision Cancer Medicine

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.

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.

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.

This article was adapted from Coping^® with Cancer magazine, July/August 2014.