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LBH589 and Bevacizumab in Patients With Recurrent High Grade Glioma

This study has been completed.
Sponsor:
Collaborators:
Brigham and Women's Hospital
Massachusetts General Hospital
Beth Israel Deaconess Medical Center
Northwestern University
University of Virginia
Genentech, Inc.
Novartis
Information provided by (Responsible Party):
Patrick Y. Wen, MD, Dana-Farber/Brigham and Women's Cancer Center
ClinicalTrials.gov Identifier:
NCT00859222
First received: March 9, 2009
Last updated: October 6, 2016
Last verified: October 2016
Results First Received: March 29, 2016  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Malignant Glioma
Interventions: Drug: LBH589
Drug: bevacizumab

  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
Participants in the Phase I study enrolled from March 2009-January 2011 and the Phase II study from June 2011-May 2013.

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
Phase I Cohort 1: Bevacizumab +LBH589 20 mg Every Week Phase I Cohort 1 participants received bevacizumab 10 mg/kg intravenously (IV) on days 1 and 15 of each 28 day cycle and the original starting LBH589 dose of 20 mg/day orally, 3x per week, every week (days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26). Participants were treated until disease progression or unacceptable toxicity.
Phase I Cohort 2: Bevacizumab + LBH589 20 mg Every Other Week Phase I Cohort 2 participants received bevacizumab 10 mg/kg intravenously (IV) on days 1 and 15 of each 28 day cycle and the amended starting LBH589 dose of 20 mg/day orally, 3x per week, every other week (Days 1, 3, 5, 15, 17, 19). Participants were treated until disease progression or unacceptable toxicity.
Phase I Cohort 3: Bevacizumab + LBH589 30 mg Every Other Week Phase I Cohort 3 participants received bevacizumab 10 mg/kg intravenously (IV) on days 1 and 15 of each 28 day cycle and LBH589 30 mg/day orally, 3x per week, every other week (Days 1, 3, 5, 15, 17, 19). Participants were treated until disease progression or unacceptable toxicity.
Phase II GBM: Bevacizumab + LBH589 30 mg Every Other Week Phase II glioblastoma (GBM) participants received the regimen established in the Phase I study (Feb 2011). Phase II participants received bevacizumab 10 mg/kg intravenously (IV) on days 1 and 15 of each 28 day cycle and LBH589 30 mg/day orally, 3x per week, every other week (Days 1, 3, 5, 15, 17, 19). Participants were treated until disease progression or unacceptable toxicity.
Phase II AG: Bevacizumab + LBH589 30 mg Every Other Week Phase II Anaplastic Glioma (AG) participants received the regimen established in the Phase I study (Feb 2011). Phase II participants received bevacizumab 10 mg/kg intravenously (IV) on days 1 and 15 of each 28 day cycle and LBH589 30 mg/day orally, 3x per week, every other week (Days 1, 3, 5, 15, 17, 19). Participants were treated until disease progression or unacceptable toxicity.

Participant Flow:   Overall Study
    Phase I Cohort 1: Bevacizumab +LBH589 20 mg Every Week   Phase I Cohort 2: Bevacizumab + LBH589 20 mg Every Other Week   Phase I Cohort 3: Bevacizumab + LBH589 30 mg Every Other Week   Phase II GBM: Bevacizumab + LBH589 30 mg Every Other Week   Phase II AG: Bevacizumab + LBH589 30 mg Every Other Week
STARTED   3   3   6   24   15 
COMPLETED   0   0   0   0   0 
NOT COMPLETED   3   3   6   24   15 
Adverse Event                2                3                6                24                15 
DLT                1                0                0                0                0 



  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.
The analysis dataset is comprised of all enrolled patients.

Reporting Groups
  Description
All Phase I Participants All phase I participants received bevacizumab 10 mg/kg intravenously (IV) on days 1 and 15 of each 28 day cycle and LBH589 according to the established dose escalation schedule.
Phase II GBM: Bevacizumab + LBH589 30 mg Every Other Week Phase II glioblastoma (GBM) participants received the regimen established in the Phase I study (Feb 2011). Phase II participants received bevacizumab 10 mg/kg intravenously (IV) on days 1 and 15 of each 28 day cycle and LBH589 30 mg/day orally, 3x per week, every other week (Days 1, 3, 5, 15, 17, 19). Participants were treated until disease progression or unacceptable toxicity.
Phase II AG: Bevacizumab + LBH589 30 mg Every Other Week Phase II Anaplastic Glioma (AG) participants received the regimen established in the Phase I study (Feb 2011). Phase II participants received bevacizumab 10 mg/kg intravenously (IV) on days 1 and 15 of each 28 day cycle and LBH589 30 mg/day orally, 3x per week, every other week (Days 1, 3, 5, 15, 17, 19). Participants were treated until disease progression or unacceptable toxicity.
Total Total of all reporting groups

Baseline Measures
   All Phase I Participants   Phase II GBM: Bevacizumab + LBH589 30 mg Every Other Week   Phase II AG: Bevacizumab + LBH589 30 mg Every Other Week   Total 
Overall Participants Analyzed 
[Units: Participants]
 12   24   15   51 
Age 
[Units: Years]
Median (Full Range)
 50 
 (30 to 71) 
 53 
 (22 to 66) 
 48 
 (31 to 69) 
 50 
 (22 to 71) 
Gender 
[Units: Participants]
       
Female   6   10   5   21 
Male   6   14   10   30 
Race/Ethnicity, Customized 
[Units: Participants]
       
White   12   16   14   42 
Non-White   0   8   1   9 
Number of Prior Relapses 
[Units: Participants]
       
 12   15   7   34 
 0   9   4   13 
 0   0   3   3 
 0   0   1   1 
Histology 
[Units: Participants]
       
glioblastoma (GBM)   10   24   0   34 
anaplastic astrocytoma (AA)   1   0   8   9 
anaplastic oligodendroglioma (AO)   0   0   5   5 
anaplastic oligoastrocytoma (AOA)   1   0   2   3 


  Outcome Measures
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1.  Primary:   LBH589 Maximum Tolerated Dose (MTD) [Phase I]   [ Time Frame: Participants were assessed every 2 weeks while on study; The observation period for MTD evaluation was the first 30 days of treatment. ]

2.  Primary:   Dose Limiting Toxicity (DLT) [Phase I]   [ Time Frame: Participants were assessed every 2 weeks while on study; The observation period for DLT evaluation was the first 30 days of treatment. ]

3.  Primary:   6-Month Progression-Free Survival (PFS6) [Phase II]   [ Time Frame: Disease was assessed radiographically to document clinical progression every cycle on treatment and post-treatment every 8 weeks up to 12 months. Participants were followed for PFS6 up to 6 months since study entry. ]

4.  Secondary:   Best Radiographic Response   [ Time Frame: Disease was assessed radiographically for response every cycle on treatment. Treatment duration in cycles was a median (range) of 2 (1-6) PI Cohort 1, 4.5 (2-6) PI Cohort 2, 6 (2-10) PI Cohort 3, 5 PII GBM and 7 PII AG. ]

5.  Secondary:   Progression-Free Survival (PFS) [Phase II]   [ Time Frame: Disease was assessed radiographically to document clinical progression every cycle on treatment and post-treatment every 8 weeks up to 12 months. ]

6.  Secondary:   Overall Survival [Phase II]   [ Time Frame: Participants were followed long-term for survival every 4 months from the end of treatment until death or lost to follow-up. Phase II participants were followed for OS up to 27 months on this study. ]

7.  Other Pre-specified:   Progression-Free Survival (PFS) [Phase I]   [ Time Frame: Disease was assessed radiographically to document clinical progression every cycle on treatment and post-treatment every 8 weeks up to 12 months. ]

8.  Other Pre-specified:   6-Month Progression-Free Survival (PFS6) [Phase I]   [ Time Frame: Disease was assessed radiographically to document clinical progression every cycle on treatment and post-treatment every 8 weeks up to 12 months. Participants were followed for PFS6 up to 6 months since study entry. ]

9.  Other Pre-specified:   Overall Survival (OS) [Phase I]   [ Time Frame: Participants were followed long-term for survival every 4 months from the end of treatment until death or lost to follow-up. Phase I participants were followed for OS up to 12.1 months on this study. ]


  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:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Patrick Y. Wen, MD
Organization: Dana-Farber Cancer Institute
phone: 617-632-2166
e-mail: Patrick_Wen@dfci.harvard.edu


Publications of Results:

Responsible Party: Patrick Y. Wen, MD, Dana-Farber/Brigham and Women's Cancer Center
ClinicalTrials.gov Identifier: NCT00859222     History of Changes
Other Study ID Numbers: 08-342
CLBH589BUS42T
Study First Received: March 9, 2009
Results First Received: March 29, 2016
Last Updated: October 6, 2016
Health Authority: United States: Food and Drug Administration