NCI's Clinical Trials Programs and Initiatives
Why Clinical Trials Are Critical to Progress against Cancer
Clinical trials are essential for moving new methods of preventing, diagnosing, and treating cancer from the laboratory to physicians' offices and other clinical settings and, ultimately, to improve care and quality of life for people with cancer.
In clinical trials, researchers carefully and methodically test drugs, medical devices, screening approaches, behavioral modifications, and other interventions. Trials are used to answer many different clinical questions relevant to all aspects of health care, such as whether a treatment can prevent cancer in people at increased risk, whether a new drug can extend the lives of patients with advanced cancer, or whether specific treatment approaches can improve patients’ quality of life. The Food and Drug Administration (FDA) typically requires proof of safety and effectiveness of a new anticancer drug in a large clinical trial before it can be used broadly in patient care.
In addition to testing new interventions, clinical trials can help determine the best use of existing interventions, test new approaches for increasing the number of people who seek follow-up care after a positive cancer screening test, and test ways to improve end-of-life care for patients.
How New Knowledge about Cancer Is Changing Clinical Trials
Over the last two decades, biomedical researchers have begun to unravel cancer’s immense complexity, drilling down to the molecular level to better understand the genetic and biological changes that drive how cancers develop, grow, and spread. Today, researchers are able to sequence the genome of an individual patient’s cancer more quickly and more cheaply than ever before, making precision medicine possible.
This greater understanding of cancer and how tumors behave at the molecular level has allowed scientists to develop a new generation of targeted drugs and immune-based therapies, identify biomarkers that can be used to guide therapy and select patients who are most likely to respond to a drug, and develop novel strategies to detect difficult-to-treat cancers early.
The practice of clinical trials is evolving to keep pace with these advances in the scientific understanding of cancer. Already, for example, investigators are conducting fewer very large trials in which all patients, regardless of the underlying biology of their cancers, are randomly assigned to receive the experimental or control treatment. These large trials often require large numbers of participants to detect an effect because, often, too few patients respond to the experimental therapy to draw a definitive conclusion.
NCI is adapting its clinical trials programs to build on new research insights that target molecular alterations and only test the experimental therapy in the selected population. This approach can increase the speed and efficiency of clinical trials, as only the patients most likely to benefit are included in the trial.
How NCI Programs Make a Difference
NCI has a broad array of programs that support clinical research, including programs that facilitate the development of new interventions, from the initial creation of candidate drugs in the lab to final testing in late-stage clinical trials.
Many NCI-supported clinical trials are designed not simply to test an intervention, but to identify the optimal approaches to treatment with the goal of improving patient outcomes. This includes trials that test combinations of therapies—including surgery, radiation therapy, chemotherapy, and new targeted agents—to determine which may be most beneficial in certain subgroups of patients. Trials like these are not typically supported by the private sector.
A hallmark of NCI trials is a commitment to involving participants who are representative of the US population—including patients of different racial, ethnic, and socioeconomic backgrounds—to ensure that trial findings are broadly applicable. In addition, data and specimens from NCI-supported trials are made available to researchers worldwide to further scientific discovery.
NCI-supported trials also incorporate translational endpoints, measures that can be used to inform translation of the findings beyond the study population. This allows investigators to learn from both positive and negative findings, and it means that trial findings may be used to inform more than just patient outcome.
Early-Phase Clinical Trials: Building on Basic and Preclinical Advances
Early-phase clinical trials, which test promising new agents in small numbers of patients, are critical to developing new cancer treatments and interventions. These initial trials set the stage for the larger trials needed to determine whether a drug is safe and effective. As cancer therapy becomes more precisely targeted to the unique molecular profile of a patient’s tumor, early-phase trials are taking on greater importance.
The researcher-physicians in NCI’s Center for Cancer Research conduct hundreds of trials each year at the NIH Clinical Center in Bethesda, MD—the only hospital in the world dedicated solely to medical research. Many of these small trials test cutting-edge treatments and technologies, often in patients with advanced cancers that no longer respond to standard therapy. These trials test new treatment and supportive care approaches, and lay the foundation for similar trials to be conducted at NCI-supported centers across the country.
The NCI Experimental Therapeutics Clinical Trials Network conducts early-stage trials of targeted therapies and combinations of therapies and is an important venue for identifying promising new treatments to test in late-stage trials funded by NCI and the private sector.
ETCTN trials enroll patients based on the molecular profiles of their tumors. Comprehensive molecular analyses of patients’ tumor and blood samples and advanced imaging studies are built into many ETCTN trials to measure specific functional changes in patient’s tumors or to identify biomarkers that may predict response to treatment.
ETCTN includes a comprehensive process for designing and launching trials, including the formation of drug-specific project teams made up of investigators with expertise in clinical, translational, and basic sciences. These investigators, from within and outside NCI, have expertise in the drugs being tested, the molecular targets of the drug or drug class, and the disease being studied. Among other tasks, the teams formulate proposals for early-stage trials of a given drug or drug combination.
NCI’s Consortia for Early Phase Prevention Trials supports research on potential prevention agents, for people at increased risk of developing cancer due to a family history of the disease or other risk factors. Institutions that are part of this program conduct small clinical trials that can tease out important details about how a potential prevention agent or intervention might work or who would be most likely to benefit from it.
Phase II and Phase III Trials: Testing Effectiveness
Phase II clinical trials provide additional evidence of biological effects against cancers, and phase III trials provide the most definitive evidence for whether a drug or treatment is effective. NCI supports a wide array of late-stage and community-based clinical trials. As part of NCI's clinical trials programs, more than 3,100 institutions and 14,000 investigators have been involved, and 20,000 to 25,000 patients have been enrolled in clinical treatment and advanced imaging trials each year over the past decade.
The cornerstone of NCI’s transformed clinical trials program, the NCTN is a network of organizations and clinicians that conduct large phase II and phase III clinical trials across the United States and Canada that help to establish new standards of care, set the stage for FDA approval of new therapies, test new approaches to radiation therapy and surgery, and validate new biomarkers. NCTN provides an infrastructure for NCI-funded treatment, screening, and diagnosis trials at over 3,000 clinical trials sites. NCTN supports several precision medicine trials that use genomic screening to identify patients who are appropriate for the trials and will match patients to the appropriate intervention arm of the trial based on the molecular profiles of their tumors. By testing treatments that are tailored to the underlying biology of patients’ tumors, these trials are designed to overcome some of the greatest challenges facing cancer research: increasing the success rate of clinical trials and the speed with which safe and effective cancer therapies are made available to patients. These trials also contribute to another important NCI goal: increasing collaboration with the private sector to improve access to promising investigational drugs or combinations of therapies.
NCORP is a national network of investigators, cancer care providers, academic institutions, and other organizations that conduct multisite cancer clinical trials and studies of diverse populations in community-based health care systems across the United States and Puerto Rico. NCORP brings cancer clinical trials and cancer care delivery research to individuals in their own communities. Treatment, imaging, prevention, screening, health-related quality of life, and comparative effectiveness trials are generating a broadly applicable evidence base that contributes to improved patient outcomes and a reduction in cancer disparities. The scope of NCORP also extends to the study of how health care delivery settings and organizations may affect treatment outcomes or preventive interventions.
Correlative and Quality of Life Studies: Improving Standard Clinical Practice
BIQSFP supports biomarker, imaging, and quality-of-life studies that are embedded in NCTN clinical trials. These studies will often be used to identify or validate targets for new drugs and investigate new tests that can predict whether a patient will respond to a given treatment, as well as test ways to enhance clinical trial design and improve clinical trial accrual and retention.
How NCI Is Supporting Cutting-Edge Clinical Trials
With a greater reliance on sophisticated technologies and more complex clinical trial designs, NCI has assembled a host of programs that provide important resources for researchers and institutions to lead and participate in NCI-supported trials. These resources help to streamline trial operations, improve efficiency, and reduce administrative burdens.
This support allows the clinicians and care providers who run trials more time to focus on patient care and research. These programs include:
The CCCT manages the expert scientific steering committees that review proposed trials and provide scientific expertise and guidance, coordinates the NCI clinical trials oversight committees—the Clinical Trials and Translational Research Advisory Committee (CTAC) and the Clinical and Translational Research Operations Committee (CTROC)—and facilitates clinical trial data reporting.
The CIRB provides human subjects protection review of studies for NCI's national multicenter cancer trials networks. Institutions across the country rely on the CIRB's national experts to ensure that studies are reviewed efficiently and with the highest ethical standards. The CIRB is structured to greatly reduce the administrative burden for institutions participating in NCI-sponsored clinical trials.
The CTSU provides researchers with easy-to-access online information about NCI-sponsored clinical trials with the goal of speeding accrual and enrollment to these trials. The CTSU provides investigators and their staff with a uniform approach to managing regulatory requirements and patient enrollment in trials, as well as providing funding information and educational materials for each trial.
The NCTN groups collect and store tissue from patients in NCTN trials in a harmonized network of tissue banks. Standard protocols have been developed to ensure that the tissue collected is of the highest quality. Computerized records of the stored samples will have important clinical details, such as the treatments received by the patients from whom the tissue was taken, treatment response, and patient outcome. Participants in NCTN trials may consent to the use of their tissue specimens for studies beyond the NCTN trial in which they are enrolled. A web-based system allows any researcher, including one who is not affiliated with the NCTN, to query the system about the availability of tissue that meets certain criteria and track the review and approval process of any request to use samples.
This public–private partnership between NCI and pharmaceutical and biotechnology companies will give investigators at NCI-Designated Cancer Centers quicker access to approved and investigational agents for use in cancer clinical trials. Eligible investigators will be able to apply for access to agents from the available formulary list and test them in new preclinical or clinical studies, including combination studies of formulary agents from different companies.