Comparing 4 approaches for stage III colon cancer

Inclusion

• +HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• +Patients must have histologically/pathologically confirmed Stage IIB, IIC, or Stage III colon adenocarcinoma with R0 resection according to AJCC 8th edition criteria.
• +No radiographic evidence of overt metastatic disease within 45 days prior to Step 1/Study entry (CT with IV contrast or MRI imaging is acceptable and must include chest, abdomen, and pelvis).
• +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.
• +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 treating investigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more → must deem the patient a candidate for all potential agents used in this trial (5FU, LV, oxaliplatin and irinotecan).
• +Availability and provision of adequate surgical tumor tissue for molecular diagnostics and confirmatory profiling.
• +Adequate hematologic function within 28 days before Step 1/Study entry defined as follows:
• +Absolute neutrophil count (ANC) must be greater than or equal to 1500/mm3;
• +Participants with benign ethnic neutropenia (BEN): ANC less than 1300 mm3 are eligible.
• +BEN (also known as constitutional neutropenia) is an inherited cause of mild or moderate neutropenia that is not associated with any increased risk for infections or other clinical manifestations. BEN is referred to as ethnic neutropenia because of its increased prevalence in people of African descent and other specific ethnic groups.
• +Platelet count must be greater than or equal to 100,000/mm3; and
• +Hemoglobin must be greater than or equal to 9 g/dL.
• +Adequate hepatic function within 28 days before Step 1/Study entry defined as follows:
• +total bilirubin must be less than or equal to ULN (upper limit of normal) for the lab and
• +alkaline phosphatase must be less than 2.5 x ULN for the lab; and
• +AST and ALT must be less than 2.5 x ULN for the lab.
• +Adequate renal function within 28 days before Step 1/Study entry defined as serum creatinine less than or equal to 1.5 x ULN for the lab or measured or calculated creatinine clearance greater than or equal to 50 mL/min using the Cockroft-Gault formula for patients with creatinine levels greater than 1.5 x ULN for the lab.
• +For Women Creatinine Clearance (mL/min) = (140 - age) x weight (kg) x 0.85 72 x serum creatinine (mg/dL) For Men Creatinine Clearance (mL/min) = (140 - age) x weight (kg) 72 x serum creatinine (mg/dL) NOTE: Adjusted body weight (AdjBW) should be used for patients that have BMI greater than or equal to 28 (less than or equal to 30% above IBW).
• +Patients receiving a coumarin-derivative anticoagulant must agree to weekly monitoring of INR if they are randomizedRandomisedWhich group you go into is decided by chance, not by you or your doctor.Read more → to ArmArmOne of the groups in a study, each receiving something different.Read more → 1 or Arm 3 and receive capecitabine.
• +Eligibility CriteriaEligibility criteriaThe full list of requirements for taking part in a study.Read more → for CohortCohortA group of participants sharing a characteristic, followed together.Read more → A Arm-2 patients on Second Randomization
• +Patient must have developed a ctDNA +ve assay during serial monitoring.
• +Patient's willingness to be re-randomized affirmed.
• +No radiographic evidence of overt metastatic disease.
• +Adequate hematologic function within 28 days before second randomization defined as follows:
• +Absolute neutrophil count (ANC) must be greater than or equal to 1500/mm3;
• +Participants with benign ethnic neutropenia (BEN): ANC less than 1300 mm3 are eligible.
• +BEN (also known as constitutional neutropenia) is an inherited cause of mild or moderate neutropenia that is not associated with any increased risk for infections or other clinical manifestations. BEN is referred to as ethnic neutropenia because of its increased prevalence in people of African descent and other specific ethnic groups.
• +Platelet count must be greater than or equal to 100,000/mm3; and
• +Hemoglobin must be greater than or equal to 9 g/dL.
• +Adequate hepatic function within 28 days before second randomization defined as follows:
• +total bilirubin must be less than or equal to ULN (upper limit of normal) for the lab and
• +alkaline phosphatase must be less than 2.5 x ULN for the lab; and
• +AST and ALT must be less than 2.5 x ULN for the lab.
• +Adequate renal function within 28 days before second randomization defined as serum creatinine less than or equal to 1.5 x ULN for the lab or measured or calculated creatinine clearance greater than or equal to 50 mL/min using the Cockroft-Gault formula for patients with creatinine levels greater than 1.5 x ULN for the lab.
• +For Women Creatinine Clearance (mL/min) = (140 - age) x weight (kg) x 0.85 72 x serum creatinine (mg/dL) For Men Creatinine Clearance (mL/min) = (140 - age) x weight (kg) 72 x serum creatinine (mg/dL)
• +The patient must have an ECOG performance status of 0 or 1.
• +The patient must continue to have an ECOG performance status of 0 or 1.
• +Pregnancy test (urine or serum according to institutional standard) done within 14 days before Step 1/Study entry must be negative (for women of childbearing potential only).
• +Pregnancy test (urine or serum according to institutional standard) done within 14 days before second randomization must be negative (for women of childbearing potential only).
• +The distal extent of the tumor must be greater than or equal to 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 resected tumor specimen and a blood specimen from patients with Stage IIB, IIC, or Stage III colon cancer must have central testing for ctDNA using the Signatera™ assay by Natera (after Step 1/Study entry and before Step2/Randomization). Patient must have sufficient tissue to meet protocolProtocolThe detailed plan a study must follow.Read more → requirements. This blood specimen for the Signatera assay must be collected after surgery (and recommended at least 14 days post surgery).
• +The interval between surgery (post-operative Day 7) and Step 1/Study entry must be no more than 60 days. NOTE: Step 1/Study Entry may occur as early as post operative Day 7, but it cannot occur beyond 60 days from the actual date of the patient's surgery.