Ph II SAHA and Bevacizumab for Recurrent Malignant Glioma Patients

NCT01738646 | Completed Phase 2 Results DMC

• 1 other identifier: Pro00024983
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

Recurrent Glioblastoma Multiforme; Malignant Glioma; Adult Brain Tumor

Keywords

vorinostat; SAHA; bevacizumab; AVASTIN; malignant glioma; GBM; glioblastoma multiforme; brain tumor

Outcome Measures

Primary Outcomes (1)

• Six-month Progression-free Survival (PFS6)

  The percentage of participants alive and progression-free at 6 months after the start of study treatment will be determined. Based on Response Assessment in Neuro-Oncology (RANO) criteria, progression is defined as a ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions; significant increase in T2/FLAIR; any new lesion; clear clinical deterioration not attributable to other causes apart from the tumor; failure to return for evaluation as a result of death or deteriorating condition; or clear progression of non-measurable disease. PFS6 will be calculated from the date study treatment started until the date of progression or death, or the date of last follow-up if participants are alive without progression. Kaplan-Meier methods will be used to estimate survival.

  6 months

Secondary Outcomes (4)

• Radiographic Response

  3 Years

• Percentage of Participants Who Experience Grade 3 or Greater, Treatment Related, Non-hematologic Toxicities.

  2.7 Years

• Median Progression-free Survival (PFS)

  3 Years

• Median Overall Survival (OS)

  3 Years

Study Arms (1)

Vorinostat & Bevacizumab

EXPERIMENTAL

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; Drug: Bevacizumab

Interventions

Vorinostat DRUG

Also known as: SAHA

Vorinostat & Bevacizumab

Bevacizumab DRUG

Also known as: Avastin

Vorinostat & Bevacizumab

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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
• 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 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)

Sponsors & Collaborators

• Duke University: lead
• Genentech, Inc.: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• 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.

  PMID: 29133513 DERIVED

Related Links

• Link to the Preston Robert Tisch Brain Tumor Center
• Duke Cancer Institute
• Duke Cancer Center - Patient Care

MeSH Terms

Conditions

Glioblastoma; Glioma; Brain Neoplasms

Interventions

Vorinostat; Bevacizumab

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Katherine Peters
• Organization: Duke Univeristy Medical Center

katherine.peters.@dm.duke.edu

919 684-3914

Study Officials

• Katherine Peters, MD, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2012
• First Posted: November 30, 2012
• Study Start: January 1, 2013
• Primary Completion: December 1, 2014
• Study Completion: February 1, 2016
• Last Updated: March 6, 2017
• Results First Posted: October 29, 2015

Record last verified: 2016-11

Locations

US (1)