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Presurgery Bortezomib for Recurrent Malignant Gliomas Followed by Postop Bortezomib & Temozolomide

This study has been completed.
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Jeffrey Raizer, Northwestern University
ClinicalTrials.gov Identifier:
NCT00990652
First received: October 6, 2009
Last updated: December 11, 2013
Last verified: December 2013
Results First Received: December 11, 2013  
Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Brain and Central Nervous System Tumors
Interventions: Drug: Bortezomib
Drug: Temozolomide

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study opened on May 21, 2009 with an accrual goal of 29 patients; the study was designed to enroll 10 patients initially and do an interim efficacy assessment. Accrual was suspended on February 11, 2011 for this analysis. The interim results did not support further accrual, and so the study was permanently closed to accrual on March 29, 2011.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Bortezomib + Temozolomide Patients receive an injection of bortezomib 1.7mg/m^2 on days 1, 4 and 8. Patients then undergo their standard of care surgery on day 8 or 9 to remove the tumor. Once recovered from surgery (approximately 14 days later), patients receive combination treatment with temozolomide and bortezomib in periods called cycles (1 cycle = 4 weeks or 28 days). Temozolomide (75 mg/m^2) is taken by mouth on days 1-7 and 14-21 of each cycle, and bortezomib (1.3 mg/m^2) is given intravenously (IV) on days 7 and 21 of each cycle. Patients continue to receive cycles of treatment until disease progression, development of unacceptable toxicity, or up to a maximum of 24 months.

Participant Flow for 3 periods

Period 1:   Pre-surgical Bortezomib
    Bortezomib + Temozolomide  
STARTED     10  
COMPLETED     9  
NOT COMPLETED     1  
Adverse Event                 1  

Period 2:   Surgical Resection
    Bortezomib + Temozolomide  
STARTED     9  
COMPLETED     9  
NOT COMPLETED     0  

Period 3:   Post-sugery Bortezomib + Temozolomide
    Bortezomib + Temozolomide  
STARTED     9  
COMPLETED     8  
NOT COMPLETED     1  
Withdrawal by Subject                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Bortezomib + Temozolomide Patients receive an injection of bortezomib 1.7mg/m^2 on days 1, 4 and 8. Patients then undergo their standard of care surgery on day 8 or 9 to remove the tumor. Once recovered from surgery (approximately 14 days later), patients receive combination treatment with temozolomide and bortezomib in periods called cycles (1 cycle = 4 weeks or 28 days). Temozolomide (75 mg/m^2) is taken by mouth on days 1-7 and 14-21 of each cycle, and bortezomib (1.3 mg/m^2) is given intravenously (IV) on days 7 and 21 of each cycle. Patients continue to receive cycles of treatment until disease progression, development of unacceptable toxicity, or up to a maximum of 24 months.

Baseline Measures
    Bortezomib + Temozolomide  
Number of Participants  
[units: participants]
  10  
Age, Customized  
[units: participants]
 
21-30 years     0  
31-40 years     0  
41-50 years     6  
51-60 years     2  
61-70 years     2  
71-80 years     0  
81-90 years     0  
Gender  
[units: participants]
 
Female     2  
Male     8  
Region of Enrollment  
[units: participants]
 
United States     10  



  Outcome Measures
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1.  Primary:   Number of Patients Surviving Without Disease Progression After 6 Months   [ Time Frame: From date of first treatment until disease progression, death, or early discontinuation of treatment (up to 24 months) ]

2.  Secondary:   Number of Participants Achieving a Response to Treatment (Either Complete or Partial Response) as Defined by MacDonald Criteria   [ Time Frame: Day of treatment post-surgery and then approximately every 8 weeks thereafter until off treatment ]

3.  Secondary:   Number of Grade 1, 2, 3, 4, and 5 Adverse Events Observed During Study Treatment (Defined by CTCAE v 3.0)   [ Time Frame: Days 1, 4, 8 pre-surgery, and then at the start of every cycle (approximately every 4 weeks) post-surgery while on treatment ]

4.  Secondary:   Overall Survival (in Days)   [ Time Frame: Days 1, 4, 8 pre-surgery, once per cycle (every 4 weeks) while on treatment post-surgery, and then every 3 months up to 2 years during follow-up ]

5.  Secondary:   Overall Survival Rate at 6 Months   [ Time Frame: After 6 months on study ]

6.  Other Pre-specified:   Correlation of Expression of NFKBIA Gene With Response to Therapy and Survival.   [ Time Frame: Tissue samples for analysis were obtained on the day of surgery for all patients ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

7.  Other Pre-specified:   Change in MGMT Methylation Status as Well as Other Methylation Patterns in Plasma   [ Time Frame: Blood samples drawn on days 1, 4, and 8 pre-surgery, and then prior to cycle 1 and every 2 cycles thereafter ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

8.  Other Pre-specified:   Pharmacokinetics of Bortezomib in Tumor Tissue Taken at the Time of Surgery.   [ Time Frame: Tissue sample taken at the time of surgery for all patients. ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Results Point of Contact:  
Name/Title: Jeffrey Raizer, MD
Organization: Northwestern University
phone: 312-503-4724
e-mail: jraizer@nmff.org


No publications provided


Responsible Party: Jeffrey Raizer, Northwestern University
ClinicalTrials.gov Identifier: NCT00990652     History of Changes
Other Study ID Numbers: NU 08C5, STU00008280
Study First Received: October 6, 2009
Results First Received: December 11, 2013
Last Updated: December 11, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board