Circulating Tumor DNA Testing in Predicting Treatment for Patients With Stage IIA Colon Cancer After Surgery

Official Title

Phase II/III Study of Circulating Tumor DNA as a Predictive Biomarker in Adjuvant Chemotherapy in Patients With Stage IIA Colon Cancer (COBRA)

Summary:

This phase II/III trial studies how well circulating tumor deoxyribonucleic acid (ctDNA) testing in the blood works in predicting treatment for patients with stage IIA colon cancer after surgery. ctDNA are circulating tumor cells that are shed by tumors into the blood. Finding ctDNA in the blood means that there is very likely some small amounts of cancer that remain after surgery. However, 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 benefit, and those who do not benefit, from receiving chemotherapy.

Trial Description

PRIMARY OBJECTIVES:

• 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) II. To compare recurrence-free survival (RFS) in "ctDNA detected" patients treated with or without adjuvant chemotherapy following resection of stage IIA colon cancer. (Phase III)

SECONDARY OBJECTIVES:

• To describe the prevalence of detectable ctDNA in patients with stage IIA colon cancer following surgical resection.
• To estimate time-to-event outcomes (overall survival [OS], recurrence-free survival [RFS], and time to recurrence [TTR]) by ctDNA marker status and treatment for patients with resected stage IIA colon cancer.
• To estimate the rate of compliance with adjuvant chemotherapy and/or active surveillance for patients with resected stage IIA colon cancer.

EXPLORATORY OBJECTIVES:

• To describe the association of quantitative ctDNA levels with time to event outcomes (RFS, OS, and TTR).
• To characterize genomic profiles associated with recurrence using a ctDNA assay in patients with resected stage IIA colon cancer.
• To model the cost effectiveness of the use of ctDNA versus standard of care in this setting.
• To evaluate performance of a ctDNA assay after incorporation of patient tumor and peripheral blood mononuclear cells.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I (BLOOD STORED AND TESTED FOR ctDNA LATER): Patients undergo active surveillance.

ARM II (BLOOD TESTED FOR ctDNA AT BASELINE): Patients are assigned to 1 of 2 groups.

GROUP I (ctDNA DETECTED): At the discretion of the investigator, patients receive either oxaliplatin intravenously (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 orally (PO) twice daily (BID) on days 1-14 repeated every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.

GROUP II (ctDNA NOT DETECTED): Patients undergo active surveillance.

After completion of study treatment, patients are followed up at 12 months and then every 6 months for 2 years.

Primary Outcome Measures:

• Clearance of circulating tumour deoxyribonucleic acid (ctDNA) (to undetectable levels) for the "baseline ctDNA detected" patient subset (Phase II)
• Recurrence-free survival (RFS) the "baseline ctDNA detected" patient subset (Phase III)

Secondary Outcome Measures:

• RFS
• Overall survival (OS)
• Time to recurrence (TTR)
• Compliance with adjuvant chemotherapy and/or active surveillance
• Incidence (presence or absence) of ctDNA in blood following resection of stage II colon cancer

Other Outcome Measures:

• Quantitative ctDNA levels
• Genomic profiles
• Cost effectiveness of the use of ctDNA versus standard of care

View this trial on ClinicalTrials.gov