March 10 2020
Researchers are currently looking into the potential ways we could make better treatment decisions for patients with colon cancer by utilizing circulating tumor DNA (ctDNA) as a blood-based biomarker. At this time, the data suggest that ctDNA can be a valuable prognostic biomarker. Specifically, patients with detectable ctDNA following their cancer resection are considered high-risk to develop recurrent disease. Patients who have no detectable ctDNA tend to do well prognostically and have a lower possibility for recurring. While current research has established the prognostic power of ctDNA, there has yet to be evidence generated that demonstrates ctDNA can help oncologists tailor therapy for patients, particularly related to the use of post-operative or adjuvant chemotherapy.
NRG Oncology’s GI005 trial, also known as the COBRA trial, is the first NCI-led clinical trial that seeks to determine if ctDNA can be used to guide the tailored treatment of patients post-operatively, specifically whether or not ctDNA can serve as a predictive biomarker on which to base adjuvant treatment decisions for patients with stage IIA colon cancer following surgery.
“NRG-GI005’s goal is to help physicians use ctDNA to determine which patients could benefit from further treatment with adjuvant chemotherapy following surgery, as current technology does not indicate which patients have been successfully treated by surgery alone versus which patients are likely to exhibit recurrence later on,” stated Van K. Morris, MD, of the University of Texas MD Anderson Cancer Center and the Principal Investigator of the COBRA trial. “The best chance that we have to treat colon cancer and avoid recurrence is by properly detecting and intervening in the early stages. NRG-GI005 could provide us with a better tool to do so.”
The COBRA trial, which opened to accrual in December 2019, is expected to enroll over 1,400 patients who have resected stage IIA colon cancer that is considered low-risk and would not normally warrant adjuvant chemotherapy under current practice standards. Patients who participate on the trial will be randomly assigned either to be under close observation, as the standard of care is today or to undergo prospective testing for ctDNA. Patients who undergo testing upfront and have detectable ctDNA would be considered high-risk for recurrence and would go on to receive six months of adjuvant chemotherapy. Patients who undergo testing and are found to have no detectable ctDNA will be considered lower risk for recurrence and will undergo active surveillance. Blood will also be collected from patients on the standard of care treatment arm to be later analyzed for ctDNA status and compared to the rate of ctDNA clearance with the patients treated with chemotherapy.
NRG Oncology partnered with Guardant Health for the COBRA trial, utilizing their LUNAR-1 assay for the conduct of this trial. The LUNAR-1 assay includes both somatic mutations and colorectal-specific methylation profiling as a part of the assay which helps to further increase the sensitivity of detecting minimal residual disease in patients.
ASCO’s Interview with Principal Investigator, Dr. Morris
NRG-GI005 on ClinicalTrials.gov