Ph II SAHA and Bevacizumab for Recurrent Malignant Glioma Patients

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Genentech
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT01738646
First received: November 28, 2012
Last updated: June 13, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Recurrent Glioblastoma Multiforme
Malignant Glioma
Adult Brain Tumor
Drug: Vorinostat
Drug: Bevacizumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Bevacizumab and Vorinostat for Recurrent WHO Grade IV Malignant Glioma Patients

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • 6-month progression-free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Radiographic Response [ Time Frame: 2.5 Years ] [ Designated as safety issue: No ]
    MRI evaluations for assessment of radiographic response and response will be classified according to the Response Assessment in Neuro-Oncology criteria. Brain MRI will be performed prior to the initiation of every other cycle. Comparisons of objective assessments, excluding progressive disease, are based upon major changes in tumor size on the Gd-MRI scan compared to the baseline scan. Determination of progressive disease is based upon comparison to the previous scan with the smallest measurements.

  • Safety & Tolerability [ Time Frame: 2.5 Years ] [ Designated as safety issue: Yes ]
    Grade 3 or greater, treatment related, non-hematologic toxicities.

  • Median progression-free survival [ Time Frame: 2.5 Years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 2.5 Years ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: January 2013
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Vorinostat
Other Name: SAHA
Drug: Bevacizumab
Other Name: Avastin

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01738646

Locations
United States, North Carolina
Duke Cancer Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Genentech
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Katherine Peters, MD, PhD Duke University
  More Information

Additional Information:
No publications provided

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT01738646     History of Changes
Other Study ID Numbers: Pro00024983
Study First Received: November 28, 2012
Last Updated: June 13, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Duke University:
vorinostat
SAHA
bevacizumab
AVASTIN
malignant glioma
GBM
glioblastoma multiforme
brain tumor

Additional relevant MeSH terms:
Glioma
Glioblastoma
Brain Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Astrocytoma
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Bevacizumab
Vorinostat
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014