Phase II Study of Bevacizumab and Vorinostat for Recurrent WHO Grade IV Malignant Glioma Patients
- Age > 18 years.
- An interval of at least 4 weeks between prior surgical resection or one week from
- 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
- 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).
- 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
- 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
- History of myocardial infarction or unstable angina within 6 months prior to study
- History of stroke or transient ischemic attack within 6 months prior to study
- 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