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Phase II Study of Bevacizumab and Vorinostat for Recurrent WHO Grade IV Malignant Glioma Patients

Phase 2
18 Years
Open (Enrolling)
Recurrent Glioblastoma Multiforme, Malignant Glioma, Adult Brain Tumor

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Trial Information

Phase II Study of Bevacizumab and Vorinostat for Recurrent WHO Grade IV Malignant Glioma Patients

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.

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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

6-month progression-free survival

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

Katherine Peters, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke University


United States: Food and Drug Administration

Study ID:




Start Date:

January 2013

Completion Date:

June 2015

Related Keywords:

  • Recurrent Glioblastoma Multiforme
  • Malignant Glioma
  • Adult Brain Tumor
  • vorinostat
  • SAHA
  • bevacizumab
  • malignant glioma
  • GBM
  • glioblastoma multiforme
  • brain tumor
  • Brain Neoplasms
  • Glioblastoma
  • Glioma



Duke Cancer CenterDurham, North Carolina  27710