This trial is active, not recruiting.

Conditions recurrent glioblastoma multiforme, malignant glioma, adult brain tumor
Treatments vorinostat, bevacizumab
Phase phase 2
Targets HDAC, VEGF
Sponsor Duke University
Collaborator Genentech, Inc.
Start date January 2013
End date December 2014
Trial size 40 participants
Trial identifier NCT01738646, Pro00024983


It has been shown that bevacizumab has significant anti-tumor activity in patients with recurrent glioblastoma multiforme. Vorinostat has modest anti-tumor activity against malignant glioma and can enhance the action of both chemotherapy and anti-angiogenics. Patients will be treated with a combination of bevacizumab and vorinostat.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
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.
vorinostat SAHA
bevacizumab Avastin

Primary Outcomes

6-month progression-free survival
time frame: 6 months

Secondary Outcomes

Radiographic Response
time frame: 2.5 Years
Safety & Tolerability
time frame: 2.5 Years
Median progression-free survival
time frame: 2.5 Years
Overall survival
time frame: 2.5 Years

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title Phase II Study of Bevacizumab and Vorinostat for Recurrent WHO Grade IV Malignant Glioma Patients
Principal investigator Katherine Peters, MD, PhD
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in March 2015.
Information provided to ClinicalTrials.gov by Duke University.