Ph II SAHA and Bevacizumab for Recurrent Malignant Glioma Patients

NCT ID: NCT01738646

Last Updated: 2017-03-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-31
• Study Completion Date: 2016-02-29

Brief Summary

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.

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.

Conditions

Recurrent Glioblastoma Multiforme; Malignant Glioma; Adult Brain Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Vorinostat

Intervention Type: DRUG

Bevacizumab

Intervention Type: DRUG

Interventions

Vorinostat

Intervention Type: DRUG

Bevacizumab

Intervention Type: DRUG

Other Intervention Names

SAHA; Avastin

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Katherine Peters, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Duke Cancer Center

Durham, North Carolina, United States

Countries

United States

References

Ghiaseddin A, Reardon D, Massey W, Mannerino A, Lipp ES, Herndon JE 2nd, McSherry F, Desjardins A, Randazzo D, Friedman HS, Peters KB. Phase II Study of Bevacizumab and Vorinostat for Patients with Recurrent World Health Organization Grade 4 Malignant Glioma. Oncologist. 2018 Feb;23(2):157-e21. doi: 10.1634/theoncologist.2017-0501. Epub 2017 Nov 13.

Reference Type: DERIVED

PMID: 29133513 (View on PubMed)

Related Links

http://www.cancer.duke.edu/btc/

Link to the Preston Robert Tisch Brain Tumor Center

http://www.dukecancerinstitute.org/

Duke Cancer Institute

http://www.dukehealth.org/cancer

Duke Cancer Center - Patient Care

Other Identifiers

Pro00024983

Identifier Type: -

Identifier Source: org_study_id