Using Cancer Cells in the Blood (ctDNA) to Determine the Type of Chemotherapy that will Benefit Patients who Have Had Surgery for Colon Cancer, (CIRCULATE-NORTH AMERICA)

Active:	Yes
Cancer Type:	Colon/Rectal Cancer Unknown Primary	NCT ID:	NCT05174169
Trial Phases:	Phase II Phase III	Protocol IDs:	NRG-GI008 (primary) NRG-GI008 NCI-2021-08397
Eligibility:	18 Years and older, Male and Female	Study Type:	Treatment
Study Sponsor:	NRG Oncology
NCI Full Details:	http://clinicaltrials.gov/show/NCT05174169

Summary

This phase II/III trial aims to determine the type of chemotherapy that will benefit patients who have had surgery for their stage II or III colon cancer based on presence or absence of circulating tumor deoxyribonucleic acid (ctDNA). In ctDNA positive patients, this trial compares the effect of usual chemotherapy versus mFOLFIRINOX. In ctDNA negative patients, this trial compares the effect of usual chemotherapy versus ctDNA testing every 3 months to determine which approach might be better to prevent colon cancer from returning. Oxaliplatin is in a class of medications called platinum-containing antineoplastic agents. It works by damaging cell’s DNA and may kill cancer cells. Leucovorin is in a class of medications called folic acid analogs. It works by protecting healthy cells from the effects of chemotherapy medications while allowing chemotherapy agent to enter and kill cancer cells. Fluorouracil is in a class of medications called antimetabolites. It stops cells from making DNA and may slow or stop the growth of cancer cells. Capecitabine is in a class of medications called antimetabolites. It Is taken up by cancer cells and breaks down to a substance that kills cancer cells. Irinotecan is in a class of antineoplastic medications called topoisomerase I inhibitors. It works by stopping the growth of cancer cells. This trial may help doctors determine what kind of chemotherapy to recommend to colon cancer patients based on the presence or absence of ctDNA after surgery for colon cancer.

Objectives

PRIMARY OBJECTIVES:
I. To compare time to ctDNA (positive [+ve]) status in ctDNA (negative [-ve]) cohort following resection of stage III colon cancer treated with immediate vs delayed (based on serial ctDNA surveillance) chemotherapy. (Phase II, ctDNA-ve Cohort [Arms 1 + 2])
II. To compare time to disease free survival (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. (Phase III, ctDNA-ve Cohort [Arms 1 + 2])
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 fluorouracil (5-FU) (or capecitabine) and oxaliplatin x 6 months or 5-FU, oxaliplatin and irinotecan x 6 months. (Phase II and III, ctDNA+ve Cohort [Arms 3 + 4])

SECONDARY OBJECTIVES:
II. To describe the prevalence of detectable ctDNA in patients with stage III colon cancer following surgical resection.
II. To estimate time-to-event outcomes (overall survival and time to recurrence) by ctDNA marker status and treatment.
III. To assess the compliance of adjuvant chemotherapy.

EXPLORATORY OBJECTIVES:
I. To explore the kinetics of quantitative ctDNA levels over time and its association with time to event outcomes (relapse free survival [RFS], overall survival [OS], and time to recurrence [TTR]).
II. To characterize genomic profiles associated with recurrence using a ctDNA assay in patients with resected colon cancer.

OUTLINE: Patients are assigned to 1 of 2 cohorts.

COHORT A: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive oxaliplatin intravenously (IV) over 2 hours, leucovorin IV over 2 hours, and fluorouracil over 2-4 minutes and then over 46-48 hours on day 1. Cycles repeat every 14 days for 6-12 cycles in the absence of disease progression or unacceptable toxicity. Patients may alternatively receive oxaliplatin IV over 2 hours on day 1 and capecitabine orally (PO) twice daily (BID) on days 1-14. Cycles repeat every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

ARM II: Patients undergo blood sample collection for serial ctDNA testing every 3-6 months for 3 years.

COHORT B: Patients are randomized to 1 of 2 arms.

ARM III: Patients receive oxaliplatin IV over 2 hours, leucovorin IV over 2 hours, and fluorouracil over 2-4 minutes and then over 46-48 hours on day 1. Cycles repeat every 14 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients may alternatively receive oxaliplatin IV over 2 hours on day 1 and capecitabine PO BID on days 1-14. Cycles repeat every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity.

ARM IV: Patients receive oxaliplatin IV over 2 hours, leucovorin IV over 2 hours, irinotecan IV over 30-90 minutes, and fluorouracil over 2-4 minutes and then over 46-48 hours on day 1. Cycles repeat every 14 days for 12 cycles in the absence of disease progression or unacceptable toxicity.

All patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study. Patients also undergo blood sample collection throughout the study.

After completion of study treatment, patients are followed up until year 5 from randomization.

Treatment Sites in Georgia

Piedmont Columbus Regional
710 Center Street
Columbus, GA 31901
www.columbusregional.com

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