Ignite Creation Date:
2025-12-26 @ 5:18 PM
Ignite Modification Date:
2025-12-29 @ 1:21 AM
Study NCT ID:
NCT00641706
Status:
COMPLETED
Last Update Posted:
2014-05-14
First Post:
2008-03-21
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Vorinostat and Bortezomib in Treating Patients With Progressive, Recurrent Glioblastoma Multiforme
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
Phase II Study of Vorinostat (SAHA) in Combination With Bortezomib (PS-341) in Patients With Recurrent Glioblastoma Multiforme
Status:
COMPLETED
Status Verified Date:
2011-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase II trial is studying how well giving vorinostat together with bortezomib works in treating patients with progressive, recurrent glioblastoma multiforme. Vorinostat and bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vorinostat together with bortezomib may kill more tumor cells.
Detailed Description:
PRIMARY OBJECTIVES:
I. To determine the clinical efficacy of vorinostat (SAHA) and bortezomib, in terms of progression-free survival (PFS) at 6 months, in patients with progressive, recurrent glioblastoma multiforme.
SECONDARY OBJECTIVES:
I. To determine the clinical efficacy of this regimen, in terms of overall survival, PFS at 12 months, time to progression, and objective response rate, in these patients.
II. To identify molecular predictors of response in baseline tumor specimens from these patients.
III. To determine molecular changes in response to this regimen in tumor specimens from patients undergoing surgery.
OUTLINE: This is a multicenter study. Patients are stratified according to planned surgery (no \[stratum 1\] vs yes \[stratum 2\]).
STRATUM 1 (NOT UNDERGOING SURGERY): Patients receive oral vorinostat (SAHA) once daily on days 1-14 and bortezomib intravenously (IV) on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
STRATUM 2 (UNDERGOING SURGERY): Patients receive oral SAHA once daily for 2 days prior to surgery and then on the day of surgery. Patients also receive bortezomib IV on the day of surgery. After receiving the 3rd dose of SAHA, patients undergo surgery to remove the tumor. Beginning at least 7 days after surgery, patients receive SAHA and bortezomib as in stratum 1.
Tumor tissue samples are collected at baseline and during surgery (stratum 2) for correlative laboratory studies. Tissue samples are analyzed for baseline total and phosphorylated AKT and p27\^KIp1 expression by IHC. Tissue samples from patients in stratum 2 are also analyzed for histone acetylation status; markers of proteasome inhibition; total and phosphorylated Bax expression by IHC; and gene expression profiles.
After completion of study therapy, patients are followed every 3 months for 2 years and then every 6 months thereafter.
I. To determine the clinical efficacy of vorinostat (SAHA) and bortezomib, in terms of progression-free survival (PFS) at 6 months, in patients with progressive, recurrent glioblastoma multiforme.
SECONDARY OBJECTIVES:
I. To determine the clinical efficacy of this regimen, in terms of overall survival, PFS at 12 months, time to progression, and objective response rate, in these patients.
II. To identify molecular predictors of response in baseline tumor specimens from these patients.
III. To determine molecular changes in response to this regimen in tumor specimens from patients undergoing surgery.
OUTLINE: This is a multicenter study. Patients are stratified according to planned surgery (no \[stratum 1\] vs yes \[stratum 2\]).
STRATUM 1 (NOT UNDERGOING SURGERY): Patients receive oral vorinostat (SAHA) once daily on days 1-14 and bortezomib intravenously (IV) on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
STRATUM 2 (UNDERGOING SURGERY): Patients receive oral SAHA once daily for 2 days prior to surgery and then on the day of surgery. Patients also receive bortezomib IV on the day of surgery. After receiving the 3rd dose of SAHA, patients undergo surgery to remove the tumor. Beginning at least 7 days after surgery, patients receive SAHA and bortezomib as in stratum 1.
Tumor tissue samples are collected at baseline and during surgery (stratum 2) for correlative laboratory studies. Tissue samples are analyzed for baseline total and phosphorylated AKT and p27\^KIp1 expression by IHC. Tissue samples from patients in stratum 2 are also analyzed for histone acetylation status; markers of proteasome inhibition; total and phosphorylated Bax expression by IHC; and gene expression profiles.
After completion of study therapy, patients are followed every 3 months for 2 years and then every 6 months thereafter.
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?: