Vorinostat in Treating Patients With Progressive or Recurrent Glioblastoma Multiforme

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00238303
First received: October 12, 2005
Last updated: May 7, 2014
Last verified: October 2011
  Purpose

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.


Condition Intervention Phase
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Recurrent Adult Brain Tumor
Drug: vorinostat
Procedure: conventional surgery
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Suberoylanilide Hydroxamic Acid (SAHA) in Patients With Recurrent Glioblastoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Proportion of Successes (Patients Alive and Progression-free) [ Time Frame: At 6 months ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Survival [ Time Frame: From study registration to date of death due to any cause or last follow-up (up to 5 years) ] [ Designated as safety issue: No ]
    Estimated using Kaplan-Meier survival curve.

  • Confirmed Tumor Response [ Time Frame: Assessed up to 5 years ] [ Designated as safety issue: No ]

    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) ] [ Designated as safety issue: No ]

    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.



Enrollment: 103
Study Start Date: September 2005
Study Completion Date: March 2010
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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.
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

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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00238303

Locations
United States, Minnesota
North Central Cancer Treatment Group
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Investigators
Principal Investigator: Evanthia Galanis North Central Cancer Treatment Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00238303     History of Changes
Obsolete Identifiers: NCT01647100
Other Study ID Numbers: NCI-2009-00646, NCI-2009-00646, CDR0000445405, NCCTG-N047B, N047B, N047B, U10CA025224
Study First Received: October 12, 2005
Results First Received: December 11, 2012
Last Updated: May 7, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on July 23, 2014