A Phase 4 Study of Regorafenib in Metastatic Colorectal Cancer - Does Educating Physicians Change Patient Outcomes?

Inclusion Criteria:

- Histologically or cytologically-proven metastatic CRC for which the decision of
treatment with regorafenib was made

- Previous treatment with fluoropyrimidine-, oxaliplatin- and irinotecan-based
chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy

- Male or female patients ≥ 18 years of age

- Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1

- Signed informed consent obtained before any study specific procedure is
performed.Patients must be able to understand and willing to sign the written ICF.

- Life expectancy of at least 12 weeks

- Adequate bone marrow, liver and renal function as assessed by the following laboratory
requirements:

1. Total bilirubin ≤ 1.5 x the upper limits of normal (ULN)

2. Alanine aminotransferase (ALT) and aspartate aminotransferease (AST)

≤ 3.0 x ULN (≤ 5 x ULN for patients with liver involvement of their cancer)

3. Alkaline phosphastase limit ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver
involvement of their cancer)

4. Lipase ≤ 1.5 x the ULN

5. Amylase ≤ 1.5 x the ULN

6. Serum creatinine ≤ 1.5 x the ULN

7. International normalized ratio (INR) ≤ 1.5 x ULN and partial thromboplastin time
(PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless
receiving treatment with therapeutic anticoagulation. Patients being treated with
anticoagulant (e.g., heparin), will be allowed to participate provided no prior
evidence of an underlying abnormality in these parameters exists. Close
monitoring of at least weekly evaluations will be performed until INR and PTT are
stable based on a pre-dose measurement as defined by the local standard of care.

8. Platelet count ≥ 100000 /mm3, hemoglobin (Hb) ≥ 9 g/dL, absolute neutrophil count
(ANC) ≥ 1500/mm3. Blood transfusion to meet the inclusion criteria will not be
allowed.

- Estimated creatinine clearance (CLcr) ≥ 30 mL/min as calculated using the
Cockroft-Gault (C-G) equation.

- Women of childbearing potential must have a blood or urine pregnancy test performed a
maximum of 7 days before start of study treatment, and a negative result must be
documented before start of study treatment.

- Women of childbearing potential and men must agree to use adequate contraception
before entering the program until at least 8 weeks after the last study drug
administration.

Exclusion Criteria:

- Unable to swallow oral medications.

- Prior use of regorafenib

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

- Uncontrolled hypertension (systolic blood pressure > 140 millimeters of mercury (mmHg)
or diastolic pressure > 90 mmHg despite optimal medical management)

- Active or clinically significant cardiac disease including:

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

2. Active coronary artery disease

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

4. 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, irrespective of severity

- Any hemorrhage or bleeding event > National Cancer Institute Common Terminology
Criteria for Adverse Events (NCI-CTCAE) Grade 3 within 4 weeks prior to the start of
study medication

- Arterial or venous thrombotic or embolic events such as cerebrovascular accident
(including transient ischemic attacks), deep vein thrombosis or pulmonary embolism
within 6 month before the start of study medication (except for adequately treated
catheter-related venous thrombosis occurring more than one month before the start of
study medication)

- Previously untreated or concurrent cancer that is distinct in primary site or
histology from colorectal cancer except cervical cancer in-situ, treated basal cell
carcinoma, or superficial bladder tumor. Patients 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 (i.e.,signature date of the ICF).