TVB- 2640 in Combination With Bevacizumab in Patients With First Relapse of High Grade Astrocytoma
Condition: Astrocytoma
MeSH terms: Astrocytoma
Intervention: Bevacizumab; TVB-2640
Intervention description: Bevacizumab is FDA approved as a treatment for recurrent Glioblastoma following failure of radiation therapy and temozolomide.; TVB-2640 is a potent and reversible inhibitor of the FASN enzyme. TVB-2640 inhibits the β-ketoacyl reductase (KR) enzymatic activity of the FASN enzyme.
Intervention MeSH terms: Bevacizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Randomized phase 2 study TVB-2640 in combination with Bevacizumab versus Bevacizumab alone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  At least 18 years of age

          -  Ability to understand the purposes and risks of the study and has signed a written
             informed consent form approved by the investigator's 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

          -  ECOG Performance Status of 0 to 2

          -  Life expectancy of at least 3 months

          -  Adequate renal and liver function: AST/ALT ≤ 3 x ULN, Bilirubin ≤ 1.5 times ULN,
             Creatinine ≤ ULN

          -  Adequate hematologic status (without hematologic support): Hemoglobin ≥ 9 g/dL, 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 IUD) with their partner from entry
             into the study through six 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 MRI or 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 NCI CTCAE v.4.03 Grade ≤ 1 from 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 necessary 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, Gastrointestinal perforation, abdominal fistula, intra-abdominal
             abscess within 1 year

          -  Inherited bleeding diathesis or coagulopathy with the risk of bleeding

          -  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