Regorafenib in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumor

Inclusion Criteria: * At least 18 years of age at the time of study entry * Histologically confirmed metastatic and/or unresectable GIST with prior failure of both conventional tyrosine kinase inhibitors, imatinib and sunitinib. * Measurable disease per RECIST 1.1. A lesion in a previously irradiated area is eligible to be considered as measurable disease as long as there is objective evidence of progression of the lesion. * ECOG Performance Status 0 or 1 * Adequate organ and marrow function as outlined in the protocol * Fully recovered from the acute effects of prior cancer therapy before initiation of study drug * Patients must be suitable for oral drug administration * Willingness to use effective means of birth control throughout the duration of clinical study and for at least 3 months after completion of study drug * Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of study drug administration Exclusion Criteria: * Use of any unapproved tyrosine kinase inhibitors or investigational agents within 2 weeks or 6 half-lives of the agent, whichever is shorter, prior to receiving study drug * Participants who have had radiotherapy within 4 weeks prior to study entry * Major surgery, or significant traumatic injury within 4 weeks prior to study entry * Presence of symptomatic or uncontrolled brain or central nervous system metastases * Prior exposure to sorafenib * Prior exposure to regorafenib * Known or suspected allergy to the investigational agent or any agent given in association with this trial * Individuals with a history of a different malignancy, other than cervical cancer in situ, basal cell or squamous cell carcinoma of the skin, are ineligible, except if they have been disease-free for at least 5 years, and are deemed by the investigator to be at low risk for recurrence of that malignancy or other primary malignancy is neither currently clinically significant nor requiring active intervention * Clinically significant cardiac arrhythmias and/or patients who require anti-arrhythmic therapy (excluding beta blockers or digoxin) * History of clinically significant cardiac disease or congestive heart failure \> NYHA class 2. Patients must not have unstable angina or new-onset angina within the last 3 months or myocardial infarction within the past 6 months * Hypertension as defined by systolic blood pressure 140-159 mmHg or diastolic blood pressure 90-99 mmHg; recurrent or persistent or symptomatic increase by \> 20 mmHg (diastolic) or to systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater than 90 mmHg if previously within normal limits, despite optimal medical management * Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months before start of study medication * Ongoing infection of Grade 3 or higher * Patients with evidence of, or history of, bleeding diathesis. Any major hemorrhage or bleeding event of Grade 3 or higher within 4 weeks of start of study medication * Non-healing wound, ulcer or bone fracture * Renal failure requiring hemo-or peritoneal dialysis * Dehydration of Grade 2 or greater * Persistent proteinuria Grade 3 or higher * Known history of HIV infection or chronic hepatitis B or C * Uncontrolled intercurrent illness * Pregnant or lactating females