Multicenter, Open-Label Phase II Study of Daily Oral Regorafenib for Chemotherapy-Refractory, Metastatic and Locally Advanced Angiosarcoma

Location:

Phoenix/Scottsdale, Ariz., Jacksonville, Fla., Rochester, Minn.

Trial status:

Open for Enrollment

Why is this study being done?

PRIMARY OBJECTIVES: I. To define the progression-free survival (PFS) at 4 months with daily oral regorafenib (160 mg) in previously treated locally advanced/metastatic angiosarcoma patients SECONDARY OBJECTIVES: I. Progression-free rate at 3 and 6 months. II. Progression-free survival. III. Overall survival (up to 5 years). IV. Response rate (by Response Evaluation Criteria in Solid Tumors [RECIST] version [v] 1.1). V. Rate and duration of tumor control (complete response [CR] + partial response [PR] + stable disease [SD]). VI. Safety/tolerability of regorafenib. OUTLINE: Patients receive regorafenib orally (PO) once daily (QD) on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months for up to 5 years.

Who is eligible to participate?

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 =< 1.5 x the upper limits of normal (ULN) - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (=< 5 x ULN for subjects with liver involvement of their cancer) - Alkaline phosphatase limit =< 2.5 x ULN (=< 5 x ULN for subjects with liver involvement of their cancer) - Lipase =< 1.5 x the ULN - Serum creatinine =< 1.5 x the ULN - International normalized ratio (INR)/partial thromboplastin time (PTT) < 1.5 x ULN - Platelet count > 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 < grade 3 (> 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 seizure disorder requiring medication, symptomatic metastatic brain or meningeal tumors - Presence of a non-healing wound, non-healing ulcer, or bone fracture - Renal failure requiring hemo-or peritoneal dialysis - Dehydration > grade 1 - Interstitial lung disease with ongoing signs and symptoms at the time of registration - Pleural effusion or ascites that causes respiratory compromise (>= 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 - Evidence of abdominal fistula, gastrointestinal (GI) perforation or intraabdominal abscess - Women who are pregnant or breast-feeding - Concurrent anti-cancer therapy (chemotherapy, surgery, immunotherapy, biologic therapy, or tumor embolization) other than study treatment (regorafenib) - Prior use of regorafenib - Prior use of sorafenib - Use of cytotoxic chemotherapy within 21 days of registration - Use of targeted therapy within two half-lives of registration - Radiation directed at target lesion within 28 days of registration - Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before registration - Therapeutic anticoagulation with Vitamin-K antagonists (e.g., warfarin) or with heparins and heparinoids; NOTE: Prophylactic anticoagulation as described below is allowed: - Low dose warfarin (1 mg orally, once daily) with prothrombin time (PT)-international normalized ratio (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 - 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

Last updated:

3/17/2014

NCT ID:

NCT02048722

IRB Number:

14-003565