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Vorinostat, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme
This study is currently recruiting participants.
Verified March 2011 by National Cancer Institute (NCI)

First Received on August 8, 2008.   Last Updated on March 23, 2011   History of Changes
Sponsor: North Central Cancer Treatment Group
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00731731
  Purpose

RATIONALE: Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving vorinostat together with temozolomide and radiation therapy may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of vorinostat when given together with temozolomide and radiation therapy and to see how well they work in treating patients with newly diagnosed glioblastoma multiforme.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Cognitive/Functional Effects
Drug: temozolomide
Drug: vorinostat
Procedure: adjuvant therapy
Procedure: cognitive assessment
Radiation: radiation therapy
Phase I
Phase II

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Phase I/II Study of Vorinostat (Suberoylanilide Hydroxamic Acid [SAHA]), Temozolomide, and Radiation Therapy in Patients With Newly Diagnosed Glioblastoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum tolerated dose of vorinostat (Phase I) [ Designated as safety issue: Yes ]
  • Overall survival (Phase II) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity (Phase I) [ Designated as safety issue: Yes ]
  • Time to tumor progression (Phase II) [ Designated as safety issue: No ]
  • Safety (Phase II) [ Designated as safety issue: Yes ]
  • Correlation of tumor molecular characteristics and expression profile with response, survival, and safety [ Designated as safety issue: Yes ]
  • Correlation of neurocognitive effects and outcome endpoints (Phase II) [ Designated as safety issue: No ]

Estimated Enrollment: 132
Study Start Date: July 2009
Estimated Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To determine the maximum tolerated dose of vorinostat when administered with temozolomide and radiotherapy in patients with newly diagnosed glioblastoma multiforme. (Phase I)
  • To determine the efficacy of this regimen, in terms of overall survival, in these patients. (Phase II)

Secondary

  • To determine the toxicity of this regimen in these patients. (Phase I)
  • To determine progression-free survival of patients treated with this regimen. (Phase II)
  • To further evaluate the safety profile of this regimen in these patients. (Phase II)
  • To determine the neurocognitive effects in these patients and correlate the results with outcome endpoints. (Phase II)

Tertiary

  • To correlate tumor molecular characteristics and expression profile with outcome.
  • To evaluate potential mechanisms of therapy resistance in tumor samples obtained at the time of tumor progression.

OUTLINE: This is a multicenter, phase I, dose-escalation study of vorinostat followed by a phase II study.

Patients undergo radiotherapy and receive oral vorinostat once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients also receive oral temozolomide once daily on days 1-42. Beginning 4-6 weeks later, patients receive oral vorinostat once daily on days 1-7 and 15-21 and oral temozolomide once daily on days 1-5. Treatment with vorinostat and temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Patients enrolled in phase II and those who are treated at the maximum tolerated dose in phase I submit tumor tissue samples for correlative laboratory studies. Studies include assessment of histone acetylation status by immunohistochemistry; gene expression profiling; and assessment of MGMT methylation status by polymerase chain reaction.

Patients enrolled in phase II and those who are treated at the maximum tolerated dose in phase I complete a neurocognitive assessment prior to, during, and after completion of study therapy. The assessment includes the Hopkins Verbal Learning Test (HVLT-R) (Revised), the Controlled Oral Word Association test from the Multilingual Aphasia Examination (COWA), the Trail Making Test A: Visual scanning speed, and the Trail Making Test B: Divided attention.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 1 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed glioblastoma multiforme, including gliosarcoma or other grade 4 astrocytoma variant (e.g., giant cell glioblastoma)
  • Bidimensionally measurable or evaluable disease by gadolinium MRI or contrast-enhanced CT scan
  • Has undergone surgery for the brain tumor within the past 2-5 weeks

PATIENT CHARACTERISTICS:

  • Karnofsky performance status (PS) 60-100% or ECOG PS 0-2
  • Life expectancy ≥ 12 weeks
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • WBC ≥ 3,000/mm^3
  • Hemoglobin ≥ 10.0 g/dL (transfusion allowed)
  • Total bilirubin ≤ 2.0 times upper normal limit (ULN)
  • AST ≤ 2.0 times ULN
  • Creatinine ≤ 1.5 mg/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 12 weeks after completion of study treatment
  • No known hypersensitivity to any of the components of vorinostat or other drugs used in the study
  • No other active malignancy within the past 3 years, except nonmelanotic skin cancer or carcinoma in situ of the cervix
  • No uncontrolled infection
  • Known HIV positivity allowed provided there is no clinical evidence of an immunocompromised state
  • No co-morbid systemic illness or other concurrent severe illness that, in the opinion of the investigator, would preclude study participation
  • No concurrent uncontrolled illness (e.g., ongoing or active infection or psychiatric illness/social situation) that would preclude study compliance
  • No myocardial infarction or unstable angina within the past 6 months
  • No congestive heart failure requiring ongoing maintenance therapy
  • No life-threatening ventricular arrhythmias
  • No congenital long QT syndrome
  • No prolonged QTc interval (i.e., QTc > 450 msec)
  • Able to take oral medications
  • Willing to provide mandatory tissue samples for research studies (for patients treated at the maximum tolerated dose)
  • Willing and able to complete neurocognitive assessments (patients enrolled in phase II and those who are treated at the maximum tolerated dose in phase I)

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior cytotoxic, non-cytotoxic, or experimental drug therapy for the brain tumor
  • No prior cranial radiotherapy
  • No prior Gliadel wafers
  • More than 7 days since prior and no concurrent Category I drugs that have a risk of causing torsades de pointes (e.g., quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, erythromycin, clarithromycin, chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, or lidoflazine)
  • More than 2 weeks since prior and no concurrent valproic acid or other histone deacetylase inhibitors
  • Concurrent corticosteroids allowed provided patient is on a fixed or decreasing dose for ≥ 5 days prior to study enrollment
  • No other concurrent investigational agents for the brain tumor
  • No other concurrent cytotoxic or non-cytotoxic drug therapy for the brain tumor
  • No concurrent stereotactic radiosurgery or brachytherapy
  • No concurrent antiretroviral therapy for HIV-positive patients
  • No concurrent treatment for another malignancy other than hormonal therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00731731

Locations
United States, Alabama
UAB Comprehensive Cancer Center Recruiting
Birmingham, Alabama, United States, 35294
Contact: Clinical Trials Office - UAB Comprehensive Cancer Center     205-934-0309        
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, Florida
Mayo Clinic - Jacksonville Recruiting
Jacksonville, Florida, United States, 32224
Contact: Clinical Trials Office - All Mayo Clinic Locations     507-538-7623        
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida Recruiting
Tampa, Florida, United States, 33612-9497
Contact: Clinical Trials Office - H. Lee Moffitt Cancer Center and Rese     800-456-7121     canceranswers@moffitt.org    
United States, Georgia
Winship Cancer Institute of Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Jeffrey J. Olson, MD     404-778-5770        
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21231-2410
Contact: Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Ce     410-955-8804     jhcccro@jhmi.edu    
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Clinical Trials Office - Warren Grant Magnusen Clinical Center     888-NCI-1937        
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Clinical Trials Office - Massachusetts General Hospital     877-726-5130        
United States, Michigan
Josephine Ford Cancer Center at Henry Ford Hospital Recruiting
Detroit, Michigan, United States, 48202
Contact: Tom Mikkelsen, MD     313-916-8641     nstom@neuro.hfh.edu    
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Lauren E. Abrey, MD     212-639-5122     abreyl@mskcc.org    
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: David A. Reardon, MD     919-684-5301     reard003@mc.duke.edu    
Wake Forest University Comprehensive Cancer Center Recruiting
Winston-Salem, North Carolina, United States, 27157-1096
Contact: Clinical Trials Office - Wake Forest University Comprehensive     336-713-6771        
United States, Ohio
Cleveland Clinic Taussig Cancer Center Recruiting
Cleveland, Ohio, United States, 44195
Contact: Clinical Trials Office - Cleveland Clinic Taussig Cancer Cente     866-223-8100        
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104-4283
Contact: Clinical Trials Office - Abramson Cancer Center of the Univers     800-474-9892        
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 Central Cancer Treatment Group
Investigators
Study Chair: Evanthia Galanis, MD Mayo Clinic
Study Chair: Patrick Y. Wen, MD Dana-Farber Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Jan C. Buckner, North Central Cancer Treatment Group
ClinicalTrials.gov Identifier: NCT00731731     History of Changes
Other Study ID Numbers: CDR0000609743, NCCTG-N0874, ABTC 0902
Study First Received: August 8, 2008
Last Updated: March 23, 2011
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
cognitive/functional effects
adult glioblastoma
adult gliosarcoma
adult giant cell glioblastoma

Additional relevant MeSH terms:
Glioblastoma
Nervous System Neoplasms
Central Nervous System Neoplasms
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Temozolomide
Dacarbazine
Vorinostat
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Histone Deacetylase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012