Regorafenib in Reducing Recurrence in Patients With Non-metastatic Rectal Cancer Who Have Completed Curative-Intent Treatment

Inclusion Criteria: * Histologically or cytologically confirmed adenocarcinoma of the rectum that was clinically staged T3, T4 or node-positive (defined as \>= N1 per American Joint Committee on Cancer \[AJCC\] 7th edition) that was treated with the following treatment with curative intent: * Curative surgical resection * Pre- or post-operative chemoradiation; and at least 3 months of adjuvant systemic chemotherapy (equivalent to 6 cycles of leucovorin calcium, fluorouracil, and oxaliplatin \[FOLFOX\] or infusional fluorouracil \[5FU\]) * No evidence of cancer within 28 days prior to start of study treatment; this should be determined by imaging of the chest, abdomen and pelvis by computed tomography (CT) and/or magnetic resonance imaging (MRI); staging of the chest using chest x-ray in lieu of CT and/or MRI should not be used for this purpose * Have an Eastern Cooperative Oncology Group (ECOG) performance status of =\< 1 * Consent to allowing his/her archival tumor tissues to be requested and analyzed; however, the non-availability or inadequate amount samples for analysis will not exclude the patient * Platelet count \>= 100,000/mm\^3; blood transfusion to meet the inclusion criteria will not be allowed * Hemoglobin (Hb) \>= 9 g/dL; blood transfusion to meet the inclusion criteria will not be allowed * Absolute neutrophil count (ANC) 1500/mm\^3; blood transfusion to meet the inclusion criteria will not be allowed * Total bilirubin =\< 1.5 x the upper limits of normal …