Ph II SAHA and Bevacizumab for Recurrent Malignant Glioma Patients
This study is ongoing, but not recruiting participants.
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
First received: November 28, 2012
Last updated: March 16, 2015
Last verified: March 2015
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.
Recurrent Glioblastoma Multiforme
Adult Brain Tumor
||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||Phase II Study of Bevacizumab and Vorinostat for Recurrent WHO Grade IV Malignant Glioma Patients
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:
| Study Start Date:
| Estimated Study Completion Date:
| Primary Completion Date:
||December 2014 (Final data collection date for primary outcome measure)
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.
Other Name: SAHA
Other Name: Avastin
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.
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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).
- 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
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
|Duke Cancer Center
|Durham, North Carolina, United States, 27710 |
Merck Sharp & Dohme Corp.
||Katherine Peters, MD, PhD
No publications provided
History of Changes
|Other Study ID Numbers:
|Study First Received:
||November 28, 2012
||March 16, 2015
||United States: Food and Drug Administration
United States: Institutional Review Board
Keywords provided by Duke University:
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on April 26, 2015
Central Nervous System Diseases
Central Nervous System Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Nervous System Diseases
Nervous System Neoplasms
Angiogenesis Modulating Agents
Histone Deacetylase Inhibitors
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs