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The patient must have an ECOG performance status of 0 or 1 |
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Patients must have histologically/pathologically confirmed colon adenocarcinoma (T1-3 |
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N1/N1c) with R0 resection accordingly to AJCC 8th edition criteria. NOTE: Patients with |
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pathologic stages II or IIIC colon adenocarcinoma with R0 resection who have a commercially |
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obtained Signatera™ ctDNA+ve assay result post-operatively meeting all timelines and |
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eligibility requirements otherwise, are eligible for enrollment and inclusion in Cohort B |
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No radiographic evidence of overt metastatic disease within 28 days prior to study entry |
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(CT with IV contrast or MRI imaging is acceptable and must include chest, abdomen, and |
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pelvis) |
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The distal extent of the tumor must be greater than or equal to 12 cm from the anal verge |
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on colonoscopy or above the peritoneal reflection as documented during surgery or on |
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pathology specimen (i.e., excluding rectal adenocarcinomas warranting treatment with |
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chemoradiation) |
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The patient must have had an en bloc complete gross resection of tumor (curative |
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resection). Patients who have had a two-stage surgical procedure, to first provide a |
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decompressive colostomy and then in a later procedure to have the definitive surgical |
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resection, are eligible |
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The resected tumor specimen and a blood specimen from patients with Stage IIIA or Stage |
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IIIB colon cancer must have central testing for ctDNA using the Signatera™ assay by Natera |
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NOTE: Patients with stage IIIA or IIIB colon cancer who otherwise meet eligibility criteria |
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and have had ctDNA status checked with the Signatera™ assay as routine care outside of the |
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study, are allowed to be enrolled, and will be retested and placed in either Cohort A or |
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Cohort B depending on the central ctDNA testing result |
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NOTE: Patients with stage II or IIIC colon cancer who otherwise meet eligibility criteria |
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and have had ctDNA status checked with the Signatera™ assay as routine care outside of the |
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study AND have a ctDNA+ve result, are allowed to be enrolled. Patients will have central |
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ctDNA testing, confirmed to be ctDNA+ve, and placed in Cohort B |
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Tumor must be documented as microsatellite stable or have intact mismatch repair proteins |
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through CLIA-approved laboratory testing. Patients whose tumors are MSI-H or dMMR are |
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excluded |
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The treating investigator must deem the patient a candidate for all potential agents used |
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in this trial (5FU, LV, oxaliplatin and irinotecan) |
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The interval between surgery (post-operative Day 7) and study entry must be no more than 60 |
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days |
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Availability and provision of adequate surgical tumor tissue for molecular diagnostics and |
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confirmatory profiling |
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Adequate hematologic function within 28 days before study entry defined as follows |
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Absolute neutrophil count (ANC) must be greater than or equal to 1500/mm3 |
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Platelet count must be greater than or equal to 100,000/mm3; and |
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Hemoglobin must be greater than or equal to 9 g/dL |
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Adequate hepatic function within 28 days before study entry defined as follows |
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total bilirubin must be less than or equal to ULN (upper limit of normal) for the lab |
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and |
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alkaline phosphatase must be less than 2.5 x ULN for the lab; and |
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AST and ALT must be less than 2.5 x ULN for the lab |
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Adequate renal function within 28 days before study entry defined as serum creatinine less |
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than or equal to 1.5 x ULN for the lab or measured or calculated creatinine clearance |
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greater than or equal to 50 mL/min using the Cockroft-Gault formula for patients with |
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creatinine levels greater than 1.5 x ULN for the lab |
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For Women Creatinine Clearance (mL/min) = (140 - age) x weight (kg) x 0.85 72 x serum |
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creatinine (mg/dL) For Men Creatinine Clearance (mL/min) = (140 - age) x weight (kg) 72 x |
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serum creatinine (mg/dL) |
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HIV-infected patients on effective anti-retroviral therapy with undetectable viral load |
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within 6 months are eligible for this trial |
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Pregnancy test (urine or serum according to institutional standard) done within 14 days |
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before study entry must be negative (for women of childbearing potential only) |
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Patients receiving a coumarin-derivative anticoagulant must agree to weekly monitoring of |
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INR if they are randomized to Arm 1 or Arm 3 and receive capecitabine |
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Eligibility Criteria for Cohort A Arm-2 patients on Second Randomization |
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Patient must have developed a ctDNA +ve assay during serial monitoring |
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Patient's willingness to be re-randomized affirmed |
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The patient must continue to have an ECOG performance status of 0 or 1 |
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No radiographic evidence of overt metastatic disease |
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Pregnancy test (urine or serum according to institutional standard) done within 14 days |
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before study entry must be negative (for women of childbearing potential only) |
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Adequate hematologic function within 28 days before randomization defined as follows |
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Absolute neutrophil count (ANC) must be greater than or equal to 1500/mm3 |
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Platelet count must be greater than or equal to 100,000/mm3; and |
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Hemoglobin must be greater than or equal to 9 g/dL |
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Adequate hepatic function within 28 days before randomization defined as follows |
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total bilirubin must be less than or equal to ULN (upper limit of normal) for the lab |
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|
and |
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alkaline phosphatase must be less than 2.5 x ULN for the lab; and |
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AST and ALT must be less than 2.5 x ULN for the lab |
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Adequate renal function within 28 days before randomization defined as serum creatinine |
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less than or equal to 1.5 x ULN for the lab or measured or calculated creatinine clearance |
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greater than or equal to 50 mL/min using the Cockroft-Gault formula for patients with |
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creatinine levels greater than 1.5 x ULN for the lab |
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For Women Creatinine Clearance (mL/min) = (140 - age) x weight (kg) x 0.85 72 x serum |
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creatinine (mg/dL) For Men Creatinine Clearance (mL/min) = (140 - age) x weight (kg) 72 x |
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serum creatinine (mg/dL) |
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Colon cancer histology other than adenocarcinoma (i.e., neuroendocrine carcinoma, sarcoma
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lymphoma, squamous cell carcinoma, etc.)
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Pathologic, clinical, or radiologic overt evidence of metastatic disease. This includes
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isolated, distant, or non-contiguous intra-abdominal metastases, even if resected
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Tumor-related bowel perforation
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History of prior invasive colon malignancy, regardless of disease-free interval
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History of bone marrow or solid organ transplantation (regardless of current
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immunosuppressive therapy needs). Bone grafts, skin grafts, corneal transplants and
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organ/tissue donation are not exclusionary
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Any prior systemic chemotherapy, targeted therapy, or immunotherapy; or radiation therapy
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administered as treatment for colorectal cancer (e.g., primary colon adenocarcinomas for
|
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which treatment with neoadjuvant chemotherapy and/or radiation is warranted are not
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permitted)
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Other invasive malignancy within 5 years before study entry. Exceptions are colonic polyps
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non-melanoma skin cancer or any carcinoma-in-situ
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Synchronous primary rectal and/ or colon cancers
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Patients with known history or current symptoms of cardiac disease, or history of treatment
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with cardiotoxic agents, should have a clinical risk assessment of cardiac function using
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the New York Heart Association Functional Classification. To be eligible for this trial
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patients should be class 2B or better
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Sensory or motor neuropathy greater than or equal to grade 2, according to CTCAE v5.0
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Blood transfusion within two weeks before collection of blood for central ctDNA testing
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Active seizure disorder uncontrolled by medication
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Active or chronic infection requiring systemic therapy
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Known homozygous DPD (dihydropyrimidine dehydrogenase) deficiency
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Patients known to have Gilbert's Syndrome or homozygosity for UGT1A128 polymorphism
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Pregnancy or lactation at the time of study entry
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Co-morbid illnesses or other concurrent disease that would make the patient inappropriate
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for entry into this study (i.e., unable to tolerate 6 months of combination chemotherapy or
|
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interfere significantly with the proper assessment of safety and toxicity of the prescribed
|
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|
regimens or prevent required follow-up)
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Ineligibility Criteria for Cohort A Arm-2 patients on Second Randomization
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Pregnancy or lactation at the time of randomization
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No longer a candidate for systemic chemotherapy (FOLFOX, CAPOX, and mFOLFIRINOX) in the
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opinion of the treating investigator
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|