Study ID: NRG-GI-005
Phase II/III study of circulating tumor DNA as a predictive biomarker in adjuvant chemotherapy in patients with stage IIA colon cancer
This trial is studying how well circulating tumor DNA (ctDNA) testing in the blood works in predicting treatment for patients with stage IIA colon cancer after surgery. In stage IIA, the cancer has grown through the wall of the colon or rectum but has not spread to nearby tissue or to the nearby lymph nodes (i.e., it is not metastatic).
ctDNA are circulating tumor cells that are shed by tumors into the blood. Finding ctDNA in the blood means there is very likely a small amount of cancer remaining after surgery. But this cancer, if detected, cannot be found on other tests usually used to find cancer, as it is too small. Testing for ctDNA levels may help identify patients with colon cancer after surgery who do and who do not benefit from receiving chemotherapy.
Researchers will take blood samples from all trial participants. Patients are randomized into two study groups. One group undergoes active surveillance, which is the current standard of care for resected stage IIA colon cancer.
Those in the other cohort are split into two groups: Those in whom ctDNA has been detected in their blood undergo a chemotherapy regimen; those in whom ctDNA is not detected undergo active surveillance.
The primary objectives of this trial are to compare the rate of ctDNA clearance in ctDNA-detected patients treated with or without adjuvant chemotherapy following resection of stage IIA colon cancer (phase II). Also, researchers seek to compare recurrence-free survival in ctDNA-detected patients treated with or without adjuvant chemotherapy following resection of stage IIA colon cancer (phase III).
Eligible patients are those with histologically/pathologically confirmed stage IIA adenocarcinoma of the colon (T3, N0, M0) with at least 12 lymph nodes examined at the time of surgical resection. The distal extent of the tumor must be ≥12 cm from the anal verge on pre-surgical endoscopy (i.e., excluding rectal adenocarcinomas warranting treatment with chemoradiation). If the patient did not undergo a pre-surgical endoscopy, then the distal extent of the tumor must be ≥12 cm from the anal verge as determined by surgical examination or pre-operative imaging.
It is appropriate for active surveillance (i.e., no adjuvant chemotherapy) at the discretion of and as documented by the evaluating oncologist based on current practice patterns.
The patient must have had an en bloc complete gross resection of tumor (curative resection) as definitive surgical cancer treatment within 14 to 60 days of study randomization. Patients who have had a two-stage surgical procedure to first provide a decompressive colostomy and then, in a later procedure, to have the definitive surgical resection, are eligible.
Those in Experimental Arm II and in whom ctDNA was detected undergo either one of the following two chemotherapy regimens:
- oxaliplatin IV over 2 hours on day 1, leucovorin IV over 2 hours on day 1, and fluorouracil IV bolus over 2-4 minutes on day 1 and then by continuous IV over 46-48 hours repeated every 14 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity; or
- oxaliplatin IV over 2 hours on day 1 and capecitabine PO BID on days 1–14 repeated every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity at the discretion of the investigator.
- Patients must have been diagnosed with stage IIA colon cancer, with no metastatic disease detected
- Must not have received any prior chemotherapy, immunotherapy or radiotherapy to treat colon cancer
- Must be willing to have their DNA checked for genetic biomarkers
- Must be willing to undergo chemotherapy, if medically appropriate