Daily Oral Regorafenib for Chemotherapy-Refractory, Metastatic and Locally Advanced Angiosarcoma

Inclusion Criteria

• Life expectancy of at least 4 months
• Histologically confirmed angiosarcoma
• Tumor deemed unresectable or metastatic
• Measurable disease per RECIST v 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Progressive disease under last palliative therapy with a history of prior ifosfamide, doxorubicin or taxane therapy for angiosarcoma; up to 4 prior therapies are allowed
• All acute toxic effects of any prior treatment have resolved to grade 1 or less (by National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE] v 4.0) at the time of registration; NOTE: Exceptions to this criterion will include alopecia and fatigue
• Total bilirubin = 100000/mm^3
• Hemoglobin > 9 g/dL
• Absolute neutrophil count > 1500/mm^3
• If baseline urine protein creatinine (UPC) >= 1, a 24-hour urine protein must be assessed; patients must have a 24-hour urine protein value 3.5 g/24 hours) to be eligible
• NOTE: Blood transfusion to meet the above criteria will not be allowed; NOTE: Patients who are prophylactically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists; close monitoring of at least weekly evaluations will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard of care
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug; post-menopausal women (defined as age >= 50 years and no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test
• Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at registration until at least 3 months after the last dose of study drug; the definition of adequate contraception will be based on the judgment of the principal investigator
• Subject must be able to swallow and retain oral medication
• Subjects must be able to understand and be willing to sign the written informed consent form; a signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure

Exclusion Criteria

• Uncontrolled hypertension (systolic pressure > 140 mmHg or diastolic pressure > 90 mmHg on repeated measurement) despite optimal medical management
• Active or clinically significant cardiac disease including:
• Congestive heart failure - New York Heart Association > 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 registration, or myocardial infarction within 6 months before registration
• Evidence or history of bleeding diathesis or coagulopathy
• Any hemorrhage or bleeding event grade 3 within 4 weeks prior to registration
• 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 informed consent
• Subjects with any previously untreated or concurrent cancer unrelated to angiosarcoma; NOTE: Exceptions include 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 registration are allowed; all treatments must have been completed at least 3 years prior to registration
• Patients with pheochromocytoma
• Patients with severe hepatic impairment (Child-Pugh class C)
• 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
• Evidence of significant central nervous system disease including se