FASN Inhibitor TVB-2640 and Bevacizumab in Treating Patients with Relapsed High Grade Astrocytoma

Inclusion Criteria

• Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator’s Institutional Review Board (IRB)/Ethics Committee
• Histologically confirmed high grade astrocytoma
• Progression following standard combined modality treatment with radiation and temozolomide chemotherapy
• Recovered from reversible toxicities of prior therapy to grade 0 or grade 1
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Life expectancy of at least 3 months
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN)
• Bilirubin =< 1.5 x ULN
• Creatinine =< ULN
• Hemoglobin >= 9 g/dL
• Absolute neutrophil count (ANC) >= 1500 cells/ml
• Platelets >= 100,000 cells/ml
• All women of childbearing potential must have a negative serum pregnancy test and male and female subjects must agree to use effective means of contraception (for example, surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an intrauterine device [IUD]) with their partner from entry into the study through three months after the last dose

Exclusion Criteria

• Receiving warfarin (or other coumarin derivatives) and is unable to switch to low molecular weight heparin (LMWH) before the first dose of study drug
• Evidence of acute intracranial or intratumoral hemorrhage either by magnetic resonance imaging (MRI) or computed tomography (CT) scan; subjects with resolving hemorrhage changes, punctuate hemorrhage, or hemosiderin are eligible
• Unable to undergo MRI scan (e.g., pacemaker)
• Received enzyme-inducing anti-epileptic agents within 14 days of study drug (e.g., carbamazepine, phenytoin, phenobarbital, primidone)
• Not recovered to a National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4.03 grade =< 1 from adverse events (AEs) (except alopecia and lymphopenia) due to surgery, antineoplastic agents, investigational drugs, or other medications that were administered prior to study drug
• Evidence of wound dehiscence
• Pregnant or breast-feeding
• Clinically significant dry eye or contact lens use
• Serious intercurrent illness such as: * Hypertension (two or more blood pressure readings performed at screening of > 150 mmHg systolic or > 100 mmHg diastolic) despite optimal treatment * Non-healing wound or ulcer * Uncontrolled life threatening cardiac arrhythmias * Untreated hypothyroidism * Uncontrolled active infection * Symptomatic congestive heart failure or unstable angina pectoris within 3 months prior to study drug * Myocardial infarction, stroke, transient ischemic attack within 6 months * Gastrointestinal perforation, abdominal fistula, intra-abdominal abscess within 1 year
• Inherited bleeding diathesis or coagulopathy with the risk of bleeding
• Human immunodeficiency virus (HIV), hepatitis B or C documented infections
• Received any of the following prior anticancer therapy: * Non-standard radiation therapy such as brachytherapy, systemic radioisotope therapy (RIT), or intra-operative radiotherapy (IORT); Note: stereotactic radiosurgery (SRS) is allowed * Non-antiangiogenic therapy (including investigational agents and small molecular kinase inhibitors) within 7 days or 5 half-lives, whichever is shorter, prior to the first dose of study drug * Biologic agents (antibodies, immune modulators, vaccines, cytokines) within 21 days prior to first dose of study drug * Nitrosoureas or mitomycin C within 42 days or metronomic/protracted low- dose chemotherapy within 14 days, or other cytotoxic chemotherapy within 28 days, prior to first dose of study drug * Prior treatment with TVB-2640 * Prior treatment with Carmustine Wafers