Clinical Trial Finder

Inclusion Criteria:

• - Age > 18 years.

• - An interval of at least 4 weeks between prior surgical resection or one week from stereotactic biopsy.

• - An interval of at least 12 weeks from the end of prior radiotherapy unless there is a new area of enhancement consistent with recurrent tumor outside of the radiation field, or there is biopsy-proven tumor progression.

• - An interval of at least 4 weeks from prior chemotherapy [6 weeks for nitrosoureas, 1 week for daily administered chemotherapy (metronomic dosing)] or investigational agent unless the patient has recovered from all anticipated toxicities associated with that therapy.

• - Eastern Cooperative Oncology Group (ECOG) 0-1.

• - Hematocrit ≥ 29%, hemoglobin ≥ 9, absolute neutrophil ≥1,500 cells/microliter, platelets ≥ 100,000 cells/microliters.

• - Serum creatinine, serum glutamic oxaloacetic transaminase(SGOT) and bilirubin < 1.5 times upper limit of normal.

• - Signed informed consent approved by the Institutional Review Board prior to patient entry.

• - No evidence of hemorrhage on the baseline MRI or CT scan other than those that are stable grade 1.

• - If sexually active, patients will take contraceptive measures for the duration of the treatments.

Medically acceptable contraceptives include:

• (1) surgical sterilization (such as a tubal ligation, hysterectomy, vasectomy), (2) approved hormonal contraceptives (such as birth control pills, patches, implants or injections), (3) barrier methods (such as a condom or diaphragm) used with a spermicide, or (4) an intrauterine device (IUD).

Exclusion Criteria:

Disease-specific exclusions.

• - More than 2 prior episodes of disease progression.

• - Prior therapy with histone deacetylase inhibitors; valproic acid is not permitted and patients previously treated with valproic acid must be off valproic acid for at least 30 days prior to initiation of study medication.

• - Prior bevacizumab therapy.

• - Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids.

• - Active infection requiring intravenous antibiotics.

• - Severe hepatic insufficiency, active viral hepatitis or HIV infection.

• - Requires therapeutic anti-coagulation with warfarin.

General medical exclusions.Subjects meeting the following criteria are ineligible for study entry:

• - Inability to comply with study and/or follow-up procedures.

Bevacizumab-specific exclusions.

• - Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications) - Any prior history of hypertensive crisis or hypertensive encephalopathy.

• - New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix E) - History of myocardial infarction or unstable angina within 6 months prior to study enrollment.

• - History of stroke or transient ischemic attack within 6 months prior to study enrollment.

• - Significant vascular disease (e.g., aortic aneurysm, aortic dissection) - Symptomatic peripheral vascular disease.

• - Evidence of bleeding diathesis or coagulopathy.

• - Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study.

• - Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment.

• - History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment.

• - Serious, non-healing wound, ulcer, or bone fracture.

• - Proteinuria at screening as demonstrated by either: - Urine protein:creatinine (UPC) ratio >= 1.0 at screening OR.

• - Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).

• - Known hypersensitivity to any component of bevacizumab.

• - Pregnant (positive pregnancy test) or lactating.

Refuse the use of effective means of contraception (men and women) in subjects of child-bearing potential

There is no effective therapy for patients with recurrent glioblastoma multiforme (GBM) hence such patients remain a major unmet need in oncology. The investigators have recently demonstrated that bevacizumab (BV), a humanized monoclonal antibody against vascular endothelial growth factor, has significant anti-tumor activity among recurrent glioblastoma multiforme patients. Vorinostat has modest anti-tumor activity against malignant glioma and can potentiate the action of both chemotherapy and anti-angiogenics. The current study is designed to evaluate the anti-tumor activity of vorinostat when combined with BV among recurrent glioblastoma multiforme patients.

Arms

Experimental: Vorinostat & Bevacizumab

Patients will be administered bevacizumab every 2 weeks and vorinostat will be taken on days 1-7 and 15-21 of each 28-day cycle at 400 mg per day.

Interventions

Drug: - Vorinostat

Drug: - Bevacizumab