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Vorinostat in Treating Patients With Progressive or Recurrent Glioblastoma Multiforme

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00238303
Recruitment Status : Completed
First Posted : October 13, 2005
Results First Posted : July 10, 2013
Last Update Posted : May 23, 2014
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE October 12, 2005
First Posted Date  ICMJE October 13, 2005
Results First Submitted Date  ICMJE December 11, 2012
Results First Posted Date  ICMJE July 10, 2013
Last Update Posted Date May 23, 2014
Study Start Date  ICMJE September 2005
Actual Primary Completion Date July 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 29, 2013)
Proportion of Successes (Patients Alive and Progression-free) [ Time Frame: At 6 months ]
Estimated using the Binomial point estimator (number of successes divided by the total number of evaluable patients) and the Binomial 95% confidence interval estimated by the exact method. Definition of progression: Bidimensionally measurable disease: >25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions. Evaluable disease (i.e., contrast enhancing mass on MRI and/or CT that is not bidimensionally measurable but clearly evaluable for response to therapy): unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians: appearance of new lesions.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 29, 2013)
  • Survival [ Time Frame: From study registration to date of death due to any cause or last follow-up (up to 5 years) ]
    Estimated using Kaplan-Meier survival curve.
  • Confirmed Tumor Response [ Time Frame: Assessed up to 5 years ]
    A confirmed tumor response will be defined as an objective status of complete response (CR), partial response (PR), or regression (REGR) on two consecutive evaluations, which include neuroimaging, lasting during a period of at least 6 weeks. Confidence intervals for the true proportion will be calculated using the exact binomial method. Bidimensionally measurable disease:≥50% reduction in product of perpendicular diameters of contrast enhancement or mass with no new lesions with the patient being on stable or decreased steroid dose. Evaluable disease (i.e., contrast enhancing mass on MRI and/or CT that is not bidimensionally measurable but clearly evaluable for response to therapy): unequivocal reduction in size of contrast-enhancement or decrease in mass effect as agreed upon independently by primary physician and quality control physicians; no new lesions. Patient should be on stable or decreased steroid dose.
  • Time to Progression [ Time Frame: From registration to disease progression (up to 5 years) ]
    Estimated using Kaplan-Meier survival curve. Definition of progression: Bidimensionally measurable disease: >25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions. Evaluable disease (i.e., contrast enhancing mass on MRI and/or CT that is not bidimensionally measurable but clearly evaluable for response to therapy): unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians: appearance of new lesions.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Vorinostat in Treating Patients With Progressive or Recurrent Glioblastoma Multiforme
Official Title  ICMJE Phase II Trial of Suberoylanilide Hydroxamic Acid (SAHA) in Patients With Recurrent Glioblastoma
Brief Summary This phase II trial is studying how well vorinostat works in treating patients with progressive or recurrent glioblastoma multiforme. Drugs used in chemotherapy, such as vorinostat, 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. Giving vorinostat before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving it after surgery may kill any remaining tumor cells.
Detailed Description

PRIMARY OBJECTIVES:

I. Determine the efficacy of vorinostat (SAHA), in terms of 6-month progression-free survival, in patients with progressive or recurrent glioblastoma multiforme.

II. Determine the safety and toxicity of this drug in these patients.

SECONDARY OBJECTIVES:

I. Determine the pharmacokinetics of this drug in these patients. II. Determine the biologic effect of this drug in target tissues, including primary tumor tissue, in these patients.

III. Correlate genetic alteration of tumors with response in patients treated with this drug.

OUTLINE: This is an open-label, multicenter study. Patients are stratified according to planned surgery (yes [stratum 1] vs no [stratum 2]) and number of prior chemotherapy regimens for progressive/recurrent disease (≤ 1 [stratum 1A] vs ≥ 2 [stratum 1B]).

STRATUM 1: Patients receive oral vorinostat (SAHA) twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. (not undergoing surgery)

STRATUM 2: Beginning 3 days prior to surgery, patients receive oral SAHA once or twice daily for a total of 6 doses. Patients then undergo surgery to remove the tumor. Beginning within 1-4 weeks after surgery, patients receive oral SAHA twice daily for 2 weeks. (undergoing surgery)

Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 5 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Adult Giant Cell Glioblastoma
  • Adult Glioblastoma
  • Adult Gliosarcoma
  • Recurrent Adult Brain Tumor
Intervention  ICMJE
  • Drug: vorinostat
    Given orally
    Other Names:
    • L-001079038
    • SAHA
    • suberoylanilide hydroxamic acid
    • Zolinza
  • Procedure: conventional surgery
    Patients undergo surgery to remove tumor
    Other Name: surgery, conventional
Study Arms  ICMJE
  • Experimental: Stratum 1 (not undergoing surgery)
    Patients receive oral vorinostat (SAHA) twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: vorinostat
    • Procedure: conventional surgery
  • Experimental: Stratum 2 (undergoing surgery)
    Beginning 3 days prior to surgery, patients receive oral SAHA once or twice daily for a total of 6 doses. Patients then undergo surgery to remove the tumor. Beginning within 1-4 weeks after surgery, patients receive oral SAHA twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: vorinostat
    • Procedure: conventional surgery
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 7, 2014)
103
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE March 2010
Actual Primary Completion Date July 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed grade 4 astrocytoma (glioblastoma multiforme), including gliosarcoma, at primary diagnosis or recurrence

    • Progressive or recurrent disease
  • Measurable or evaluable disease by MRI or CT scan
  • Performance status - ECOG 0-2
  • WBC ≥ 3,000/mm^3
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 8 g/dL
  • AST ≤ 3 times upper limit of normal (ULN)
  • Bilirubin normal
  • Creatinine ≤ 1.5 times ULN
  • No myocardial infarction within the past 6 months
  • No congestive heart failure
  • No life-threatening ventricular arrhythmia requiring ongoing maintenance therapy
  • No known HIV positivity
  • Not immunocompromised except if related to the use of corticosteroids
  • No known hypersensitivity to any of the components of the study drug
  • No uncontrolled infection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 6 months after completion of study treatment
  • No other malignancy
  • No other severe disease that would preclude study participation
  • Prior adjuvant chemotherapy allowed
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
  • More than 2 weeks since prior small molecule cell cycle inhibitor
  • Concurrent corticosteroids allowed as long as dose has been stable for ≥ 1 week
  • At least 8 weeks since prior radiotherapy

    • Must have evidence of tumor progression by MRI or CT scan after radiotherapy
  • More than 6 weeks since prior stereotactic radiosurgery or interstitial brachytherapy, unless 1 of the following criteria is met:

    • There is a separate lesion by MRI outside of the prior treatment field
    • There is evidence of recurrent disease by biopsy, MRI spectroscopy, or positron-emission tomography scan
  • More than 2 weeks since prior valproic acid
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00238303
Other Study ID Numbers  ICMJE NCI-2009-00646
NCI-2009-00646 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000445405
NCCTG-N047B
N047B ( Other Identifier: North Central Cancer Treatment Group )
N047B ( Other Identifier: CTEP )
U10CA025224 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Evanthia Galanis North Central Cancer Treatment Group
PRS Account National Cancer Institute (NCI)
Verification Date October 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP