Testing the Use of BRAF-Targeted Therapy After Surgery and Usual Chemotherapy for BRAF-Mutated Colon Cancer

Inclusion Criteria:

• PRE-REGISTRATION (STEP 0) ELIGIBILITY CRITERIA:

• BRAF V600 mutational status may be determined either locally or by central testing.This testing is mandatory prior to registration to determine eligibility. Tissuesubmission should be initiated as soon after surgery as possible. For tumorsevaluated at local laboratories, formalin-fixed paraffin-embedded (FFPE) tumortissue must still be submitted for central confirmation of BRAF status

• REGISTRATION (STEP 1) ELIGIBILITY CRITERIA:

• Histologically-proven stage III (any T [Tx, T1, T2, T3, or T4], N1-2M0; includesN1C) or high-risk (pT4) stage II colon adenocarcinoma. Tumors must be deemed tooriginate in the colon including tumors that extend into/involve the small bowel (e.g. those at the ileocecal valve) and must have been completely resected

• BRAF V600E mutation

• MMR proficient (pMMR) or microsatellite stable (MSS) tumor

• Histologic documentation: adenocarcinoma

• Stage: III (any T [Tx, T1, T2, T3, or T4], N1-2M0; includes N1C) or high-risk II (pT4)

• Tumor site: colon

• Patients must have received at least 3 months of adjuvant chemotherapy with eitherleucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX) (minimum of 5 cycles) orcapecitabine and oxaliplatin (CAPOX) (minimum of 3 cycles)

• Adjuvant therapy must be completed at most 8 weeks prior to registration

• No other prior medical therapy (chemotherapy, immunotherapy, biologic, or targetedtherapy) or radiation therapy for the current colon cancer is permitted

• Not pregnant and not nursing, because this study involves an agent that has knowngenotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearingpotential only, a negative pregnancy test done =< 7 days prior to registration isrequired

• Age >= 18 years

• Eastern Cooperative Oncology Group (ECOG) performance status: 0-2

• Absolute neutrophil count (ANC) >= 1.0 x 10^9/L

• Platelet count >= 75 x 10^9/L

• Hemoglobin > 9.0 g/dL

• Total bilirubin =< 1.5 x upper limit of normal (ULN)

• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x ULN

• Corrected QT (QTc) Interval =< 480 msec

• Creatinine = calculated (calc.) creatinine clearance >= 40 mL/min

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviraltherapy with undetectable viral load within 6 months are eligible for this trial

• No medical condition such as uncontrolled infection, uncontrolled diabetes mellitus,or cardiac disease which, in the opinion of the treating physician, would make thisprotocol unreasonably hazardous for the patient

• Patients with known history or current symptoms of cardiac disease or history oftreatment with cardiotoxic agents in the last 12 months, should have a clinical riskassessment of cardiac function using the New York Heart Association FunctionalClassification. To be eligible for this trial, patients should be class 2B or better

• No uncontrolled or poorly-controlled hypertension (> 180 mmHg systolic or > 130 mmHgdiastolic)

• No history of allergic reactions attributed to compounds of chemical or biologiccomposition similar to those of cetuximab

• No "currently active" second malignancy other than non-melanoma skin cancers orcervical carcinoma in situ. Patients are not considered to have a "currently active"malignancy if they have completed therapy and are free of disease for >= 3 years

• Patients are not considered to have a "currently active" malignancy if they hada gastric or bowel carcinoid < 1 cm, ductal carcinoma in situ (DCIS)/lobularcarcinoma in situ (LCIS) of the breast without invasive cancer, or endometrialdysplasia/carcinoma in situ

• Patients are not considered to have a "currently active" malignancy if they hada sebaceous neoplasm (sebaceous adenoma, sebaceous epithelioma, sebaceousadenocarcinoma, keratoacanthoma, and squamous cell carcinoma) that wasnoninvasive

• No known medical condition causing an inability to swallow oral formulations ofagents

• No residual Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0grade >= 2 toxicity from prior chemotherapy, with the exception of grade 2 alopeciaor neuropathy

• Drugs that prolong the QTc interval should be avoided if possible, as encorafenibcan prolong the QTc interval. Drugs that are generally accepted to have a risk ofcausing Torsades de Pointes should be discontinued or replaced with drugs that donot carry this risk if at all possible. Patients who receive potentialQTc-prolonging medications should be monitored closely

• Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed duringtreatment on this study. Patients on strong CYP3A4 inhibitors must discontinue thedrug for 14 days prior to registration on the study

• Chronic concomitant treatment with strong CYP3A4 inducers is not allowed duringtreatment on this study. Patients must discontinue the drug 14 days prior toregistration on the study

Exclusion Criteria: N/A