The ECOG-ACRIN Cancer Research Group has received federal approval to add a quality-of-life research study, COMmunication and Education in Tumor Profiling (EAQ152) or 'COMET' to the NCI-MATCH (EAY131) trial, already underway. Using feedback surveys before and after a patient receives their tumor gene testing to select cancer treatment, the COMET study will gather data to determine whether increasing knowledge about the limitations and benefits of the test can reduce a patient's level of distress about the process. The trial will open later this month.
The ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) is leading the study with funding provided by the National Cancer Institute (NCI) and the National Human Genome Research Institute, both institutes of the National Institutes of Health.
Precision medicine refers to the tailoring of treatment based on the characteristics of each individual, and tumor gene testing is used as the basis for selecting the treatment.
"This study is looking at the process of cancer patients going through tumor gene testing, and essentially, gathering data on their hopes and expectations going into the testing experience, and then looking at what happens to them coming out of the experience," said lead researcher Angela R. Bradbury, MD, a medical oncologist at the University of Pennsylvania who specializes in medical ethics and health policy.
As an ancillary study to the NCI-MATCH trial, the COMET study will utilize patients who register for tumor gene testing to determine their eligibility to enroll in one of NCI-MATCH's two dozen trial arms. Each arm is testing the effectiveness of a particular drug or drug combination designed to work against a specific gene abnormality that drives cancer growth.
As patients continue to enroll at a rapid pace in the NCI-MATCH trial, COMET will accept these patients on a first-come, first-served basis. Patients will have a very small window of time to enroll in COMET (no more than two weeks after registering for NCI-MATCH) because they must begin the COMET study before they receive the results of their tumor gene test from NCI-MATCH.
Researchers are projecting that NCI-MATCH will reach its goal of enrolling 5,000 patients for tumor gene screening by the end of 2017.
The COMET study has two very different independent research objectives.
Genetic Education Study
The genetic education study, enrolling 400 patients, uses a randomized control design to test the hypothesis that the knowledge that patients gain by completing a self-guided online genetic education program before receiving the results of their tumor gene testing will be associated with lower levels of distress (anxiety, depression, and cancer worry).
In the module, a patient learns that tumor gene testing may reveal either gene abnormalities that arise over a lifetime (somatic), potential inherited (germline) changes, neither, or both. If a non-inherited (somatic) change is found in the tumor, the patient will learn that there may, or more often, may not be a drug or drug combination that works against that gene abnormality. If an inherited (germline) change is suspected, which is a rare finding, the patient learns that there is potentially a genetic disease that can be passed down in their family. Learning this can help a patient and their family understand their risk and plan for medical management, if recommended.
"The number one question patients ask after receiving their tumor test results is 'Is this mutation something inherited and will it affect my family as well as me?," said Dr. Bradbury.
Any suspected inherited (germline) findings must be confirmed through further testing. Germline genetic testing cannot predict an exact risk for developing cancer. Again, this finding is rare.
Image to come"Many of us physicians are already having regular conversations with our patients about the benefits and limitations of tumor profiling, so we have a lot of experience with the topic, but there is no data regarding patients' experience and what they carry through the process," said NCI-MATCH study chair Keith T. Flaherty, MD, a medical oncologist at Massachusetts General Hospital Cancer Center. "The COMET study won't immediately change the practice of doctors because we will keep counseling patients in our own way. However, it should provide data on whether supplemental education will improve a patient's overall experience with genetic testing and, if so, will change how we navigate patients through this process."
In a study of patient attitudes towards personalized medicine and genetic testing, published in the American Society of Clinical Oncology's Journal of Oncology Practice in 2014, Stacy W. Gray, MD, AM and colleagues asked patients about the disadvantages of somatic genetic testing. The majority of patients (71 percent) reported potential disadvantages, such as loss of hope, disappointment, and unwanted information.
Dr. Flaherty continued: "What levels of distress do patients carry through the process of tumor testing? If their test comes back with a gene abnormality identified for them, are they inordinately or overly optimistic and see their future as bright? Conversely, if the test finds nothing, are they unduly concerned about their future? These are the types of outcomes data we are seeking in the COMET study," he said.
Genetic Counseling Pilot
COMET's secondary objective is a small pilot study of 100 patients. It will assess the feasibility and preliminary outcomes of providing genetic counseling by telephone from experts at the University of Pennsylvania to the rare number of patients in whom a potential inherited (germline) mutation is found.
Dr. Flaherty explained: "This is a known issue in the tumor profiling world, and it's part of the genetic testing process that we really haven't worked out yet, particularly at the national level. At major cancer centers where there are genetic counselors, there is very likely already a workflow in place, in terms of how such findings are handled and how patients and their families are counseled. But on the national scale, the NCI National Clinical Trials Network and the NCI Community Oncology Research Program are in many locations where there is no genetic counseling. In NCI-MATCH, two-thirds of the enrollments are in community-based sites. Will genetic counseling by phone solve this problem?"
"This part of the COMET study was developed at the University of Pennsylvania outside of the NCI-MATCH trial, but we have found a great opportunity to deploy it via NCI-MATCH, to see how well it will function on a national level," said Dr. Bradbury.
COMET's two research aims are independent in that patients are not required to participate in the primary genetic education study to be eligible for the genetic counseling pilot. Although COMET is an ancillary study to the NCI-MATCH trial, patient participation in either or both components of the COMET study is not required but presented as an option to patients.
The ClinicalTrials.gov identifier for the COMET study is NCT02823652.
About the ECOG-ACRIN Cancer Research Group
The ECOG-ACRIN Cancer Research Group is a membership-based scientific organization that designs and conducts cancer research involving adults who have or are at risk of developing cancer. ECOG-ACRIN comprises nearly 1100 member institutions in the United States and around the world. Approximately 12,000 physicians, translational scientists, and associated research professionals from the member institutions are involved in Group research, which is organized into three scientific programs: Cancer Control and Outcomes, Therapeutic Studies, and Biomarker Sciences. ECOG-ACRIN is supported primarily through National Cancer Institute research grant funding, but also receives funding from private sector organizations through philanthropy and collaborations. It is headquartered in Philadelphia, Pa. For more information, visit http://www.