SARC024: A Blanket Protocol to Study Oral Regorafenib in Patients With Selected Sarcoma Subtypes

Exclusion Criteria

• •Patients with documentation of well differentiated liposarcoma only (of the well differentiated/dedifferentiated liposarcoma family) are specifically excluded, owing to its characteristically slow growth. If high grade areas are suspected (dedifferentiation), but not proved by pathology analysis (e.g. after primary resection of a well-differentiated liposarcoma), a biopsy must be performed to demonstrate the high-grade dedifferentiated disease
• •Prior systemic therapy with a small molecule oral kinase inhibitor, including but not limited to: pazopanib, sunitinib, sorafenib, everolimus, sirolimus, vemurafenib, dasatinib and trametinib
• •Previous assignment to treatment during this study. Subjects permanently withdrawn from study participation will not be allowed to re-enter study. Patients who progress on placebo are specifically allowed to enroll on the treatment arm of the study if they meet all other entry criteria
• •Concurrent, clinically significant, active malignancies within 12 months of study enrollment
• •Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol
• •Major surgery within 28 days prior to study registration or those patients who have not recovered adequately from prior surgery
• •Patients who have received wide field radiotherapy ≤ 28 days (defined as \> 50% of volume of pelvis bones or equivalent) or limited field radiation for palliation \< 14 days prior to study registration or those patients who have not recovered adequately from side effects of such therapy
• •Patients who have received prior systemic therapy \< 14 days prior to study registration or have not recovered adequately from toxicities to CTCAE v. 4.03 grade 1 or less; prior investigational therapy may not have been given \< 5 half-lives of last dose of treatment, or \< 14 days, whichever is greater
• •Patients who have had prior autologous, or allogeneic bone marrow transplant
• •Uncontrolled hypertension (systolic pressure \>140 mm Hg or diastolic pressure \> 90 mm Hg \[NCI-CTCAE v 4.0\] on repeated measurement) despite optimal medical management
• •Active or clinically significant cardiac disease including: Congestive heart failure-New York Heart Association (NYHA) \> 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 randomization, or myocardial infarction within 6 months before randomization
• •Evidence or history of bleeding diathesis
• •Any hemorrhage or bleeding event ≥ NCI CTCAE Grade 3 within 4 weeks prior to study 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 start of study treatment
• •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 NCI-CTCAE v 4.03
• •Presence of a non-healing wound, non-healing ulcer, or benign bone fracture (patients with stress insufficiency fractures e.g. from osteoporosis or pathological fracture from tumor are eligible for study)
• •Patients with seizure disorder requiring medication
• •Proteinuria \> 100 mg/dl on urine analysis
• •Interstitial lung disease with ongoing signs and symptoms at the time of informed consent
• •Pleural effusion or ascites that causes respiratory compromise (≥ NCI-CTCAE version 4.03 Grade 2 dyspnea)
• •History of organ allograft (including corneal transplant).
• •Known or suspected allergy or hypersensitivity to regorafenib, or excipients of the formulations given during the course of this trial
• •Any malabsorption condition.
• •Women who are pregnant or breast-feeding.
• •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
• •Inability to comply with protocol required procedures
• •Use of any herbal remedy (e.g. St. John wort \[Hypericum perforatum\])