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