Study of Colorectal Cancer Patients (Stage IIIC) With Either Regorafenib or Standard of Care (No Treatment) After Adjuvant FOLFOX

Previous assignment to treatment during this study. Subjects permanently withdrawn from study participation will not be allowed to re-enter study.

Uncontrolled hypertension (systolic pressure \>140 mm Hg or diastolic pressure \> 90 mm Hg \[NCI-Common Toxicity Criteria for Adverse Effects (CTCAE) v4.03\] on repeated measurement) despite optimal medical management.

Evidence of remaining tumor

Has local or distant metastasis

Previous antiangiogenic treatment

Abnormal hematological, renal, or liver function

Impaired pulmonary function

Evidence of ≥ Grade 2 neuropathy

Active or clinically significant cardiac disease including:

* Congestive heart failure - New York Heart Association (NYHA) \> Class II.

* Active coronary artery disease.

* Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin.

* Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before randomization, or myocardial infarction within 6 months before randomization.

Evidence or history of bleeding diathesis or coagulopathy.

Any hemorrhage or bleeding event ≥ NCI CTCAE Grade 3 within 4 weeks prior to start of study medication.

Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within 6 months of start of study treatment.

Subjects with any previously untreated or concurrent cancer that is distinct in primary site or histology from breast cancer except cervical cancer in-situ, treated basal cell carcinoma, or superficial bladder tumor. Subjects surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before randomization are allowed. All cancer treatments must be completed at least 3 years prior to study entry (ie, signature date of the informed consent form).

Patients with phaeochromocytoma.

Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy.

Ongoing infection \> Grade 2 NCI-CTCAE v4.03.

Presence of a non-healing wound, non-healing ulcer, or bone fracture.

Dehydration Grade ≥ 1 NCI-CTCAE v4.03.

Patients with seizure disorder requiring medication.

Persistent proteinuria ≥ Grade 3 NCI-CTCAE v4.03 (\> 3.5 g/24 hrs, measured by urine protein: creatinine ratio on a random urine sample).

Interstitial lung disease with ongoing signs and symptoms at the time of informed consent.

Pleural effusion or ascites that causes respiratory compromise (≥ NCI-CTCAE version 4.03 Grade 2 dyspnea).

History of organ allograft (including corneal transplant).

Known or suspected allergy or hypersensitivity to any of the study drugs, study drug classes, or excipients of the formulations given during the course of this trial.

Any malabsorption condition.

Women who are pregnant or breast-feeding.

Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.

Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results.

Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) other than study treatment (regorafenib, other agents being investigated in combination with regorafenib).

Prior use of regorafenib.

Concurrent use of another investigational drug or device therapy (ie, outside of study treatment) during, or within 4 weeks of trial entry (signing of the informed consent form).

Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication.

Therapeutic anticoagulation with Vitamin-K antagonists (eg, warfarin) or with heparins and heparinoids.

o However, prophylactic anticoagulation as described below is allowed:

* Low dose warfarin (1 mg orally, once daily) with PT-INR ≤ 1.5 x ULN is permitted. Infrequent bleeding or elevations in PT-INR have been reported in some subjects taking warfarin while on regorafenib therapy. Therefore, subjects taking concomitant warfarin should be monitored regularly for changes in PT, PT-INR, or clinical bleeding episodes.

* Low dose aspirin (≤ 100 mg daily).

* Prophylactic doses of heparin.

Use of any herbal remedy (eg, St. John's wort \[Hypericum perforatum\]) Note: Granulocyte colony-stimulating factor (G-CSF) and other hematopoietic growth factors may be used in the management of acute toxicity, such as febrile neutropenia, when clinically indicated or at the investigator's discretion. However, they may not be substituted for a required dose reduction. Subjects are permitted to take chronic erythropoietin.

What this study is about