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

  • STATUS
    Recruiting
  • End date
    Apr 30, 2027
  • participants needed
    1408
  • sponsor
    NRG Oncology
Updated on 23 October 2022
platelet count
cancer
calcium
absolute neutrophil count
fluorouracil
international normalized ratio
oxaliplatin
capecitabine
tumor cells
leucovorin
colon cancer

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.

Description

PRIMARY OBJECTIVES:

I. 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:

I. To describe the prevalence of detectable ctDNA in patients with stage IIA colon cancer following surgical resection.

II. 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.

III. To estimate the rate of compliance with adjuvant chemotherapy and/or active surveillance for patients with resected stage IIA colon cancer.

EXPLORATORY OBJECTIVES:

I. To describe the association of quantitative ctDNA levels with time to event outcomes (RFS, OS, and TTR).

II. To characterize genomic profiles associated with recurrence using a ctDNA assay in patients with resected stage IIA colon cancer.

III. To model the cost effectiveness of the use of ctDNA versus standard of care in this setting.

IV. 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.

Details
Condition Colon Adenocarcinoma, Stage IIA Colon Cancer AJCC v8
Treatment Capecitabine, fluorouracil, Leucovorin calcium, Oxaliplatin, Leucovorin, Patient Observation
Clinical Study IdentifierNCT04068103
SponsorNRG Oncology
Last Modified on23 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
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
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 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
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
Availability and provision of adequate surgical tumor tissue for molecular diagnostics and confirmatory profiling
Absolute neutrophil count (ANC) must be >= 1200/mm^3 (within 28 days before randomization)
Platelet count must be >= 100,000/mm^3 (within 28 days before randomization); and
Hemoglobin must be >= 9 g/dL (within 28 days before randomization)
Total bilirubin must be =< ULN (upper limit of normal) for the lab (within 28 days before randomization) unless the patient has a chronic grade 1 bilirubin elevation due to Gilbert?s disease or similar syndrome involving slow conjugation of bilirubin; and
Alkaline phosphatase must be < 2.5 x ULN for the lab (within 28 days before randomization); and
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be < 1.5 x ULN for the lab (within 28 days before randomization)
Serum creatinine =< 1.5 x ULN for the lab or measured or calculated creatinine clearance >= 50 mL/min using the Cockcroft-Gault formula for patients with creatinine levels > 1.5 x ULN for the lab (within 28 days before randomization)
Pregnancy test (urine or serum according to institutional standard) done within 14 days before randomization must be negative (for women of childbearing potential only)
Patients receiving a coumarin-derivative anticoagulant must agree to weekly monitoring of international normalized ratio (INR) if they are randomized to Arm 2 and receive capecitabine

Exclusion Criteria

Colon cancer histology other than adenocarcinoma (i.e., neuroendocrine carcinoma, sarcoma, lymphoma, squamous cell carcinoma, etc.)
Pathologic, clinical, or radiologic evidence of overt metastatic disease. This includes isolated, distant, or non-contiguous intra-abdominal metastases, even if resected (including the presence of satellite nodules constituting N1c disease in the absence of lymph node involvement)
Tumor-related bowel perforation
History of prior invasive colon malignancy, regardless of disease-free interval
History of organ transplantation
Any prior systemic chemotherapy, targeted therapy, or immunotherapy; or radiation therapy administered as treatment for colorectal cancer (e.g., primary rectal adenocarcinomas for which treatment with neoadjuvant chemoradiation is warranted are not permitted)
Other invasive malignancy within 5 years before randomization. Exceptions are colonic polyps, non-melanoma skin cancer or carcinoma-in-situ including those of the cervix and breast (DCIS)
Synchronous primary rectal and/or colon cancers
Antineoplastic therapy (e.g., chemotherapy, targeted therapy, or immunotherapy) within 5 years before randomization. (For the purposes of this study, hormonal therapy is not considered chemotherapy.)
Uncontrolled cardiac disease, in the opinion of the treating medical oncologist, that would preclude the use of any of the drugs included in the GI005 treatment regimen. This includes but is not limited to
Clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or indwelling temporary pacemaker
Ventricular tachycardia or supraventricular tachycardia that requires treatment with class Ia antiarrhythmic drugs (e.g., quinidine, procainamide, disopyramide) or class III antiarrhythmic drug (e.g., sotalol, amiodarone, dofetilide). Use of other antiarrhythmic drugs is permitted
Second- or third-degree atrioventricular (AV) block unless treated with a permanent pacemaker
Complete left bundle branch block (LBBB) unless treated with a permanent pacemaker
Sensory or motor neuropathy >= grade 2, according to Common Terminology Criteria for
Active seizure disorder uncontrolled by medication
Adverse Events (CTCAE) version (v) 5.0
Active or chronic infection requiring systemic therapy
Known homozygous DPD (dihydropyrimidine dehydrogenase) deficiency
Pregnancy or lactation at the time of randomization
Co-morbid illnesses or other concurrent disease that, in the judgement of the clinician obtaining informed consent, would make the patient inappropriate for entry into this study (i.e., unable to tolerate 6 months of combination chemotherapy or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens or prevent required follow-up)
Prior testing with any available ctDNA test as part of the management of colon cancer
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