Study | Research Studies | School of Medicine

NRG-GI008: COLON ADJUVANT CHEMOTHERAPY BASED ON EVALUATION OF RESIDUAL DISEASE (CIRCULATE-US)

Primary Objective

This Phase II/III trial will evaluate the what kind of chemotherapy to recommend to patients based on the presence or absences of circulating tumor DNA (ctDNA) after surgery for colon cancer. ctDNA-ve Cohort (Arms 1 + 2): Phase II: To compare time to ctDNA (+ve) status in ctDNA (-ve) cohort following resection of stage III colon cancer treated with immediate vs delayed (based on serial ctDNA surveillance) chemotherapy. Time to positive event is defined as time from randomization to the first ctDNA positive result for the immediate arm (Arm 1) and to the 2nd ctDNA positive result for the delayed arm (Arm 2) to allow for the potential effect of delayed adjuvant chemotherapy. Patients recurred without a positive ctDNA result will be considered to have ctDNA positive status at the time of recurrence for both study arms. Phase III: To compare time to DFS event (recurrence, second primary colorectal cancer or death) in ctDNA (-ve) cohort following resection of stage III colon cancer treated with immediate vs delayed (based on serial ctDNA surveillance) chemotherapy. ctDNA+ve Cohort (Arms 3 + 4): Phase II and III: To compare time to DFS event (recurrence, second primary colorectal cancer or death) in ctDNA (+ve) cohort following resection of colon cancer treated with 5-FU (or capecitabine) and oxaliplatin x 6 months or 5-FU, oxaliplatin and irinotecan x 6 months.

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Description

Currently, there are no biomarkers validated prospectively in randomized studies for resected colon cancer to determine need for adjuvant chemotherapy. However, circulating tumor DNA (ctDNA) shed into the bloodstream represents a highly specific and sensitive approach (especially with serial monitoring) for identifying microscopic or residual tumor cells in colon cancer patients and may outperform traditional clinical and pathological features in prognosticating risk for recurrence. Colon cancer patients who do not have detectable ctDNA (ctDNA-) are at a much lower risk of recurrence and may not need adjuvant chemotherapy. Furthermore, for colon cancer pts with detectable ctDNA (ctDNA+) who are at a very high risk of recurrence, the optimal adjuvant chemotherapy regimen has not been established. We hypothesize that for pts whose colon cancer has been resected, ctDNA status may be used to risk stratify for making decisions about adjuvant chemotherapy.

Details

Age

Adult

Eligibility

- Patients must have histologically/pathologically confirmed Stage IIIA or Stage IIIB colon adenocarcinoma (T1-3, N1/N1c) with R0 resection accordingly to AJCC 8th edition criteria. NOTE: Patients with pathologic stages II or IIIC colon adenocarcinoma with R0 resection who have a commercially obtained Signatera ctDNA+ve assay result post-operatively meeting all timelines and eligibility requirements otherwise, are eligible for enrollment and inclusion in Cohort B. - No radiographic evidence of overt metastatic disease within 28 days prior to study entry (CT with IV contrast or MRI imaging is acceptable and must include chest, abdomen, and pelvis). - The distal extent of the tumor must be ≥ 12 cm from the anal verge on colonoscopy or above the peritoneal reflection as documented during surgery or on pathology specimen (i.e., excluding rectal adenocarcinomas warranting treatment with chemoradiation). - The patient must have had an en bloc complete gross resection of tumor (curative resection). 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. - The resected tumor specimen and a blood specimen from patients with Stage IIIA or Stage IIIB colon cancer must have central testing for ctDNA using the Signatera assay by Natera. - Tumor must be documented as microsatellite stable or have intact mismatch repair proteins through CLIA-approved laboratory testing. Patients whose tumors are MSI-H or dMMR are excluded. - The interval between surgery (post-operative Day 7) and study entry must be no more than 60 days. - NOT PERMITTED: Any prior systemic chemotherapy, targeted therapy, or immunotherapy; or radiation therapy administered as treatment for colorectal cancer (e.g., primary colon adenocarcinomas for which treatment with neoadjuvant chemotherapy and/or radiation is warranted are not permitted).Detailed eligibility criteria is available on clinicaltrials.gov. These requirements will be discussed with your doctor and/or study representative. Click the NCT number link below to learn more about this study on ClinicalTrials.gov

Locations

Cherry Creek Medical Center
Greeley Campus
Harmony Campus
Highlands Ranch Hospital
Lone Tree Medical Center
Medical Center of the Rockies
Memorial Hospital Central
Memorial Hospital North
Poudre Valley Hospital
University of Colorado Hospital

Principal Investigator

Chris Lieu

Study ID

Protocol Number: 22-0916

More information available at ClinicalTrials.gov: NCT05174169

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