Vorinostat in Treating Patients With Progressive or Recurrent Glioblastoma Multiforme

NCT ID: NCT00238303

Last Updated: 2014-05-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 103 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-09-30
• Study Completion Date: 2010-03-31

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.

Conditions

Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Recurrent Adult Brain Tumor

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

vorinostat

Intervention Type: DRUG

Given orally

conventional surgery

Intervention Type: PROCEDURE

Patients undergo surgery to remove tumor

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.

Group Type: EXPERIMENTAL

vorinostat

Intervention Type: DRUG

Given orally

conventional surgery

Intervention Type: PROCEDURE

Patients undergo surgery to remove tumor

Interventions

vorinostat

Given orally

Intervention Type: DRUG

conventional surgery

Patients undergo surgery to remove tumor

Intervention Type: PROCEDURE

Other Intervention Names

L-001079038; SAHA; suberoylanilide hydroxamic acid; Zolinza; surgery, conventional

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Evanthia Galanis

Role: PRINCIPAL_INVESTIGATOR

North Central Cancer Treatment Group

Locations

North Central Cancer Treatment Group

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

NCI-2009-00646

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000445405

Identifier Type: -

Identifier Source: secondary_id

NCCTG-N047B

Identifier Type: -

Identifier Source: secondary_id

N047B

Identifier Type: OTHER

Identifier Source: secondary_id

N047B

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA025224

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00646

Identifier Type: -

Identifier Source: org_study_id

NCT01647100

Identifier Type: -

Identifier Source: nct_alias