Clinical trial NCT00238303: Vorinostat in Treating Patients With Progressive or Recurrent Glioblastoma Multiforme
Official title: Phase II Trial of Suberoylanilide Hydroxamic Acid (SAHA) in Patients With Recurrent Glioblastoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Recurrent Adult Brain Tumor
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2005-10-13
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Proportion of Successes (Patients Alive and Progression-free)
timeFrame: At 6 months
Secondary outcomes:
measure: Survival
timeFrame: From study registration to date of death due to any cause or last follow-up (up to 5 years)
measure: Confirmed Tumor Response
timeFrame: Assessed up to 5 years
measure: Time to Progression
timeFrame: From registration to disease progression (up to 5 years)
Other outcomes:
Locations:
city: Rochester
country: United States
facility: North Central Cancer Treatment Group
state: Minnesota
Study officials:
affiliation: North Central Cancer Treatment Group
name: Evanthia Galanis
role: PRINCIPAL_INVESTIGATOR
References: