Vorinostat in Treating Patients With Progressive or Recurrent Glioblastoma Multiforme

Adult Glioblastoma Clinical Trial

Official title:

Phase II Trial of Suberoylanilide Hydroxamic Acid (SAHA) in Patients With Recurrent Glioblastoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00238303
• Other study ID #: NCI-2009-00646
• Secondary ID: NCI-2009-00646CD
• Status: Completed
• Phase: Phase 2
• First received: October 12, 2005
• Last updated: May 7, 2014
• Start date: September 2005
• Est. completion date: March 2010

Study information

• Verified date: October 2011
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT01647100

Recruitment information / eligibility

• Status: Completed
• Enrollment: 103
• Est. completion date: March 2010
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• vorinostat
Given orally

Procedure:
• conventional surgery
Patients undergo surgery to remove tumor

Locations

Country	Name	City	State
United States	North Central Cancer Treatment Group	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Successes (Patients Alive and Progression-free)	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.	At 6 months	No
Secondary	Survival	Estimated using Kaplan-Meier survival curve.	From study registration to date of death due to any cause or last follow-up (up to 5 years)	No
Secondary	Confirmed Tumor Response	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.	Assessed up to 5 years	No
Secondary	Time to Progression	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.	From registration to disease progression (up to 5 years)	No