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Vorinostat and Temozolomide in Treating Patients With Malignant Gliomas
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), November 2008
Sponsors and Collaborators: North American Brain Tumor Consortium
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00268385
  Purpose

RATIONALE: Drugs used in chemotherapy, such as vorinostat and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Vorinostat may help temozolomide work better by making tumor cells more sensitive to the drug. Giving vorinostat together with temozolomide may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of vorinostat when given together with temozolomide in treating patients with malignant gliomas.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: temozolomide
Drug: vorinostat
Phase I

MedlinePlus related topics: Cancer
Drug Information available for: Temozolomide Suberoylanilide hydroxamic acid
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: Phase I Study of Vorinostat (Suberoylanilide Hydroxamic Acid [SAHA]) in Combination With Temozolomide in Patients With Malignant Gliomas

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment: 77
Study Start Date: December 2005
Estimated Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose (MTD) of vorinostat in combination with temozolomide in patients with malignant gliomas.
  • Characterize the safety profile of vorinostat in combination with temozolomide in these patients.

Secondary

  • Characterize the pharmacokinetics of vorinostat (SAHA) in combination with temozolomide in these patients.
  • Determine efficacy of vorinostat (SAHA) in combination with temozolomide as measured by objective response in these patients.

Exploratory

  • Correlate response to treatment with the molecular phenotype of the tumor in these patients.

OUTLINE: This is a 2-part, multicenter, dose-escalation study of vorinostat.

  • Part 1: Patients receive oral vorinostat once or twice daily on days 1-7 and 15-21 OR once or twice daily on days 1-7. Patients also receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity. Beginning in course 2, some patients may receive a higher dose of temozolomide. Treatment may continue beyond 13 courses at the discretion of the investigator.

Cohorts of 3-6 patients receive escalating doses of vorinostat during course 1 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.

  • Part 2: Patients receive vorinostat and temozolomide as in part 1*. NOTE: *Beginning in course 2, all patients receive a higher dose of temozolomide.

Cohorts of 3-6 patients receive de-escalating doses of vorinostat (beginning at the MTD determined in part 1) during courses 1 and 2 until the MTD for part 2 is determined. The MTD is defined as in part 1. An additional 6 patients are treated at the MTD.

After completion of study treatment, patients are followed periodically for survival.

PROJECTED ACCRUAL: A total of 77 patients will be accrued for this study.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically proven intracranial malignant glioma, including the following subtypes:

    • Glioblastoma multiforme
    • Gliosarcoma
    • Anaplastic astrocytoma
    • Anaplastic oligodendroglioma
    • Anaplastic mixed oligoastrocytoma
    • Malignant astrocytoma NOS (not otherwise specified)
    • Original histology of a low-grade glioma and a subsequent histological diagnosis of a malignant glioma
  • Patients who have progressed on temozolomide are ineligible
  • Patients in part 1 of this study must meet the following requirements:

    • Stable disease or progression after radiation therapy (except if they have progressed on temozolomide therapy) OR recurrent disease after treatment for any number of prior relapses
    • Must have recovered from the toxic effects of prior therapy
    • 28 days since prior investigational agent
    • 28 days since prior cytotoxic therapy

      • 23 days since prior temozolomide for patients on a standard regimen (i.e., 5 days every 28 days)
    • 14 days since prior vincristine
    • 42 days since prior nitrosoureas
    • 21 days since prior procarbazine administration
    • 7 days since prior non-cytotoxic agents (e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc.) except as a radiosensitizer
    • Patients who have recently undergone resection of recurrent or progressive disease must meet the following conditions:

      • Recovered from the effects of surgery
      • Residual disease following resection is not mandated for eligibility into the study
    • Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis by positron emission tomography or thallium scanning, MR spectroscopy or surgical documentation of disease
  • Patients in part 2 of this study must meet the following requirements:

    • Stable disease after radiation therapy

      • Concurrent temozolomide with radiation therapy or radiation therapy alone, is the only prior therapy permitted
    • No recurrent disease
  • Must be willing to participate in the pharmacokinetic studies

PATIENT CHARACTERISTICS:

  • Life expectancy > 8 weeks
  • Karnofsky performance status ≥ 60
  • WBC > 3,000/mm^3
  • Absolute neutrophil count > 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin > 10 g/dL (transfusion allowed)
  • SGOT < 2 times upper limit of normal (ULN)
  • Bilirubin < 2 times ULN
  • Creatinine < 1.5 mg/dL
  • Pregnant women are excluded
  • Women of childbearing potential must have a negative pregnancy test
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of the study
  • Breastfeeding should be discontinued
  • Must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy
  • No history of any other cancer, except non-melanoma skin cancer or carcinoma in-situ of the cervix, unless in complete remission and off of all therapy for that disease for a minimum of 3 years
  • Must not have active infection or serious intercurrent medical illness
  • Must not have any disease that will obscure toxicity or dangerously alter drug metabolism
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat or other agents used in study

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 2 weeks since prior valproic acid
  • At least 3 weeks since radiation therapy
  • No patients who are known to be HIV positive and are receiving combination antiretroviral therapy
  • No other investigational agents
  • No other anticancer therapy (including chemotherapy, radiation, hormonal treatment or immunotherapy) of any kind is permitted during the study period
  • No concurrent routine prophylactic use of filgrastim (G-CSF)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00268385

Locations
United States, California
Jonsson Comprehensive Cancer Center at UCLA Recruiting
Los Angeles, California, United States, 90095-1781
Contact: Clinical Trials Office - Jonsson Comprehensive Cancer Center a     888-798-0719        
UCSF Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94115
Contact: Clinical Trials Office - UCSF Helen Diller Family Comprehensi     877-827-3222        
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Patrick Y. Wen, MD     617-632-2166     patrick_wen@dfci.harvard.edu    
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10021
Contact: Lisa M. DeAngelis, MD     212-639-7997        
United States, North Carolina
Duke Comprehensive Cancer Center Recruiting
Durham, North Carolina, United States, 27710
Contact: David A. Reardon, MD     919-668-1409     reard003@mc.duke.edu    
United States, Pennsylvania
UPMC Cancer Centers Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Clinical Trials Office - UPMC Cancer Centers     412-647-8073        
United States, Texas
M. D. Anderson Cancer Center at University of Texas Recruiting
Houston, Texas, United States, 77030-4009
Contact: Clinical Trials Office - M. D. Anderson Cancer Center at the U     713-792-3245        
United States, Wisconsin
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center Recruiting
Madison, Wisconsin, United States, 53792-6164
Contact: Clinical Trials Office - University of Wisconsin Paul P. Carbo     608-262-5223        
Sponsors and Collaborators
North American Brain Tumor Consortium
Investigators
Principal Investigator: Patrick Y. Wen, MD Dana-Farber Cancer Institute
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Publications of Results:
Wen PY, Puduvalli V, Kuhn J, et al.: Phase I study of vorinostat (suberoylanilide hydroxamic acid) in combination with temozolomide (TMZ) in patients with malignant gliomas (NABTC 04-03). [Abstract] J Clin Oncol 25 (Suppl 18): A-2039, 2007.

Study ID Numbers: CDR0000450762, NABTC-0403
Study First Received: December 20, 2005
Last Updated: December 2, 2008
ClinicalTrials.gov Identifier: NCT00268385  
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
adult anaplastic oligodendroglioma
adult glioblastoma
adult gliosarcoma
adult mixed glioma
adult anaplastic astrocytoma
adult giant cell glioblastoma
recurrent adult brain tumor

Study placed in the following topic categories:
Glioblastoma
Astrocytoma
Vorinostat
Central Nervous System Neoplasms
Temozolomide
Recurrence
Brain Neoplasms
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma
Oligodendroglioma
Glioma
Gliosarcoma
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Anticarcinogenic Agents
Anti-Inflammatory Agents
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Neoplasms, Nerve Tissue
Nervous System Diseases
Enzyme Inhibitors
Protective Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Sensory System Agents
Analgesics, Non-Narcotic
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Peripheral Nervous System Agents
Analgesics
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Neoplasms, Neuroepithelial
Central Nervous System Agents
Alkylating Agents

ClinicalTrials.gov processed this record on January 15, 2009