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Trial record 36 of 42 for:    Malignant Hyperthermia 5

LBH589 and Bevacizumab in Patients With Recurrent High Grade Glioma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00859222
Recruitment Status : Completed
First Posted : March 10, 2009
Results First Posted : November 28, 2016
Last Update Posted : March 14, 2017
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

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Malignant Glioma
Interventions Drug: LBH589
Drug: bevacizumab
Enrollment 51
Recruitment Details 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  
Arm/Group Title 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
Hide Arm/Group Description 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 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 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 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 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.
Period Title: Overall Study
Started 3 3 6 24 15
Completed 0 0 0 0 0
Not Completed 3 3 6 24 15
Reason Not Completed
Adverse Event             2             3             6             24             15
DLT             1             0             0             0             0
Arm/Group Title 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
Hide Arm/Group Description 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 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 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 of all reporting groups
Overall Number of Baseline Participants 12 24 15 51
Hide Baseline Analysis Population Description
The analysis dataset is comprised of all enrolled patients.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 12 participants 24 participants 15 participants 51 participants
50
(30 to 71)
53
(22 to 66)
48
(31 to 69)
50
(22 to 71)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 24 participants 15 participants 51 participants
Female
6
  50.0%
10
  41.7%
5
  33.3%
21
  41.2%
Male
6
  50.0%
14
  58.3%
10
  66.7%
30
  58.8%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 12 participants 24 participants 15 participants 51 participants
White 12 16 14 42
Non-White 0 8 1 9
Number of Prior Relapses  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 12 participants 24 participants 15 participants 51 participants
1 12 15 7 34
2 0 9 4 13
3 0 0 3 3
4 0 0 1 1
Histology  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 12 participants 24 participants 15 participants 51 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
1.Primary Outcome
Title LBH589 Maximum Tolerated Dose (MTD) [Phase I]
Hide Description The MTD LBH589 in combination with bevacizumab 10 mg/kg intravenously (IV) on days 1 and 15 of each 28 day cycle is determined by the number of patients who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as the highest dose at which fewer than one-third of patients experience a DLT. If no DLTs are observed, the MTD is not reached but the highest dose received may be the Recommended Phase II Dose (RP2D). The MTD was not reached with 0 of 6 DLTs observed in the highest dose cohort but due to safety concerns higher doses of LBH589 with bevacizumab were neither planned nor tested. The RP2D was 30 mg/day orally, 3x per week, every other week.
Time Frame Participants were assessed every 2 weeks while on study; The observation period for MTD evaluation was the first 30 days of treatment.
Hide Outcome Measure Data
Hide Analysis Population Description
All PI participants who received at least one dose of the study drug were evaluable for MTD.
Arm/Group Title All Phase I Participants
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 12
Measure Type: Number
Unit of Measure: mg/day orally, 3x per wk, every other wk
30
2.Primary Outcome
Title Dose Limiting Toxicity (DLT) [Phase I]
Hide Description A DLT was defined as an adverse event that (a) is related to the LBH589 and/or bevacizumab with an attribution of possible, probable, or definite, and (b) occurs during and/or begins during the first 30 days of the study treatment, and (c) meets any of the following criteria: grade 3 thrombocytopenia; grade 4 neutropenia lasting 7 days; grade 4 anemia lasting 7 days despite transfusion or growth factors; febrile neutropenia if ANC<0.5 x10^9/L; a QT interval corrected for heart rate (QTc) of 500–515 msec that did not stabilize to <480 msec after one week; a second occurrence of QTc 500–515 msec; any QTc >515 msec; any deep vein thrombosis (DVT) or pulmonary embolism (PE) while on fully therapeutic anticoagulation therapy; Grade 3 proteinuria lasting 14 days; or any other clinically significant Grade 3 toxicity despite maximal medical therapy lasting 7 days, any Grade 4 toxicity despite maximal medical therapy; or any Grade 3 or 4 toxicity resulting in study drug discontinuation.
Time Frame Participants were assessed every 2 weeks while on study; The observation period for DLT evaluation was the first 30 days of treatment.
Hide Outcome Measure Data
Hide Analysis Population Description
All PI participants who received at least one dose of the study drug were evaluable for DLT.
Arm/Group Title 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
Hide Arm/Group Description:
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 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 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.
Overall Number of Participants Analyzed 3 3 6
Measure Type: Number
Unit of Measure: participants with DLT
1 0 0
3.Primary Outcome
Title 6-Month Progression-Free Survival (PFS6) [Phase II]
Hide Description PFS6 is the proportion of patients remaining alive and progression-free at 6-months from study entry. Progressive disease was established based on RANO criteria (Wen et al JCO 2010).
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.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with measurable disease present at baseline and received at least one dose of the study drug were evaluable for PFS6.
Arm/Group Title Phase II GBM: Bevacizumab + LBH589 30 mg Every Other Week Phase II AG: Bevacizumab + LBH589 30 mg Every Other Week
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 24 15
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.304
(0.124 to 0.507)
0.467
(0.21 to 0.73)
4.Secondary Outcome
Title Best Radiographic Response
Hide Description Radiographic response was established based on Response Assessment in Neuro-Oncology (RANO) criteria (Wen et al JCO 2010) with 5 potential categories: Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive disease (PD) and Unknown status.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with measurable disease present at baseline and received at least one dose of the study drug were evaluable for response.
Arm/Group Title 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
Hide Arm/Group Description:
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 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 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 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 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.
Overall Number of Participants Analyzed 3 3 6 24 15
Measure Type: Number
Unit of Measure: participants
Complete Response 0 0 0 0 0
Partial Response 0 1 2 7 4
Stable Disease 2 2 3 14 9
Progressive Disease 1 0 1 3 2
5.Secondary Outcome
Title Progression-Free Survival (PFS) [Phase II]
Hide Description PFS is defined as the time from study entry to the earliest documentation of disease progression or death. Patients alive without evidence of PD were censored at the date of last disease assessment.
Time Frame Disease was assessed radiographically to document clinical progression every cycle on treatment and post-treatment every 8 weeks up to 12 months.
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Hide Analysis Population Description
All PII participants with measurable disease present at baseline and received at least one dose of the study drug were evaluable for PFS.
Arm/Group Title Phase II GBM: Bevacizumab + LBH589 30 mg Every Other Week Phase II AG: Bevacizumab + LBH589 30 mg Every Other Week
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 24 15
Median (Full Range)
Unit of Measure: months
5
(3 to 9)
7
(2 to 10)
6.Secondary Outcome
Title Overall Survival [Phase II]
Hide Description OS is defined as the time from study entry to death or date last known alive.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of the study drug were followed for OS.
Arm/Group Title Phase II GBM: Bevacizumab + LBH589 30 mg Every Other Week Phase II AG: Bevacizumab + LBH589 30 mg Every Other Week
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 24 12
Median (Full Range)
Unit of Measure: months
9
(6 to 19)
17
(5 to 27)
7.Other Pre-specified Outcome
Title Progression-Free Survival (PFS) [Phase I]
Hide Description PFS is defined as the time from study entry to the earliest documentation of disease progression or death. Patients alive without evidence of PD were censored at the date of last disease assessment. Progressive disease was established based on Response Assessment in Neuro-Oncology (RANO) criteria (Wen et al JCO 2010).
Time Frame Disease was assessed radiographically to document clinical progression every cycle on treatment and post-treatment every 8 weeks up to 12 months.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with measurable disease present at baseline and received at least one dose of the study drug were evaluable for PFS.
Arm/Group Title All Phase I Participants
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 12
Median (Full Range)
Unit of Measure: months
4.3
(1.1 to 9.5)
8.Other Pre-specified Outcome
Title 6-Month Progression-Free Survival (PFS6) [Phase I]
Hide Description PFS6 is the proportion of patients remaining alive and progression-free at 6-months from study entry. Progressive disease was established based on Response Assessment in Neuro-Oncology (RANO) criteria (Wen et al JCO 2010).
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.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with measurable disease present at baseline and received at least one dose of the study drug were evaluable for PFS6.
Arm/Group Title All Phase I Participants
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 12
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.25
(0.063 to 0.551)
9.Other Pre-specified Outcome
Title Overall Survival (OS) [Phase I]
Hide Description OS is defined as the time from study entry to death or date last known alive.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of the study drug were followed for OS.
Arm/Group Title All Phase I Participants
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 12
Median (Full Range)
Unit of Measure: months
8.2
(4.8 to 12.1)
Time Frame Assessed each treatment cycle from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 2 (1-6) Phase I Cohort 1, 4.5 (2-6) Phase I Cohort 2, 6 (2-10) Phase I Cohort 3, 5 Phase II GBM and 7 Phase II AG.
Adverse Event Reporting Description Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with LBH589 and/or bevacizumab treatment-attribution of at least possibly and grade 3 or higher per CTCAEv3. Other AEs were defined as events with LBH589 and/or bevacizumab treatment-attribution of at least possibly and grades 1 or 2 per CTCAEv3.
 
Arm/Group Title 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
Hide Arm/Group Description 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 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 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 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 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.
All-Cause Mortality
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
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
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
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/3 (33.33%)   1/3 (33.33%)   2/6 (33.33%)   12/24 (50.00%)   7/15 (46.67%) 
Blood and lymphatic system disorders           
Hematologic-other  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Gastrointestinal disorders           
Esophagus, hemorrhage  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/24 (4.17%)  0/15 (0.00%) 
General disorders           
Fatigue  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/24 (4.17%)  1/15 (6.67%) 
Investigations           
ADH secretion abnormality (eg SIADH)  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
ALT, SGPT  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  2/24 (8.33%)  0/15 (0.00%) 
Lymphopenia  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  2/24 (8.33%)  1/15 (6.67%) 
Neutrophils  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  2/24 (8.33%)  1/15 (6.67%) 
Platelets  1  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%)  3/24 (12.50%)  3/15 (20.00%) 
QTc interval  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/24 (4.17%)  0/15 (0.00%) 
Weight loss  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Metabolism and nutrition disorders           
Hyperglycemia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Hyponatremia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Hypophosphatemia  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  3/24 (12.50%)  2/15 (13.33%) 
Musculoskeletal and connective tissue disorders           
Musculoskeletal/soft tissue-other  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/24 (4.17%)  1/15 (6.67%) 
Nervous system disorders           
CNS, hemorrhage  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Head/headache  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Psychiatric disorders           
Confusion  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Vascular disorders           
Hypertension  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Thrombosis/thrombus/embolism  1  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  4/24 (16.67%)  0/15 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
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
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/3 (100.00%)   3/3 (100.00%)   6/6 (100.00%)   21/24 (87.50%)   15/15 (100.00%) 
Blood and lymphatic system disorders           
Hemoglobin  1  1/3 (33.33%)  0/3 (0.00%)  1/6 (16.67%)  2/24 (8.33%)  3/15 (20.00%) 
Cardiac disorders           
Cardiac-ischemia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Endocrine disorders           
Hyopthyroidism  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/24 (0.00%)  0/15 (0.00%) 
Hyopthyroidism  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  2/24 (8.33%)  1/15 (6.67%) 
Hyperthyroidism, thyrotoxicosis  1  0/3 (0.00%)  0/3 (0.00%)  2/6 (33.33%)  1/24 (4.17%)  1/15 (6.67%) 
Hypoparathyroidism  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Eye disorders           
Dry eye syndrome  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/24 (4.17%)  0/15 (0.00%) 
Gastrointestinal disorders           
Abdomen, pain  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/24 (0.00%)  2/15 (13.33%) 
Anus, hemorrhage  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Constipation  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  2/24 (8.33%)  0/15 (0.00%) 
Diarrhea w/o prior colostomy  1  0/3 (0.00%)  1/3 (33.33%)  5/6 (83.33%)  14/24 (58.33%)  10/15 (66.67%) 
Dry mouth  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/24 (4.17%)  0/15 (0.00%) 
Dyspepsia  1  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  1/24 (4.17%)  1/15 (6.67%) 
Dysphagia  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/24 (0.00%)  1/15 (6.67%) 
Gastritis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
GI-other  1  1/3 (33.33%)  0/3 (0.00%)  2/6 (33.33%)  1/24 (4.17%)  2/15 (13.33%) 
Hemorrhoids  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Muco/stomatitis (symptom) oral cavity  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/24 (4.17%)  0/15 (0.00%) 
Muco/stomatitis by exam, oral cavity  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/24 (4.17%)  0/15 (0.00%) 
Nausea  1  1/3 (33.33%)  0/3 (0.00%)  2/6 (33.33%)  5/24 (20.83%)  5/15 (33.33%) 
Oral cavity, hemorrhage  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Vomiting  1  0/3 (0.00%)  0/3 (0.00%)  2/6 (33.33%)  3/24 (12.50%)  3/15 (20.00%) 
General disorders           
Constitutional, other  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Edema limb  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/24 (4.17%)  1/15 (6.67%) 
Fatigue  1  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Fatigue  1  0/3 (0.00%)  2/3 (66.67%)  4/6 (66.67%)  14/24 (58.33%)  7/15 (46.67%) 
Pain-other  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/24 (4.17%)  0/15 (0.00%) 
Infections and infestations           
Febrile neutropenia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Infection Gr0-2 neut, vagina  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/24 (4.17%)  0/15 (0.00%) 
Infection-other  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Injury, poisoning and procedural complications           
Wound - non-infectious  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  2/24 (8.33%)  0/15 (0.00%) 
Investigations           
Alkaline phosphatase  1  1/3 (33.33%)  0/3 (0.00%)  1/6 (16.67%)  1/24 (4.17%)  1/15 (6.67%) 
ALT, SGPT  1  0/3 (0.00%)  0/3 (0.00%)  3/6 (50.00%)  2/24 (8.33%)  6/15 (40.00%) 
Amylase  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
AST, SGOT  1  1/3 (33.33%)  0/3 (0.00%)  4/6 (66.67%)  4/24 (16.67%)  4/15 (26.67%) 
Creatinine  1  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Leukocytes  1  2/3 (66.67%)  0/3 (0.00%)  4/6 (66.67%)  3/24 (12.50%)  6/15 (40.00%) 
Lipase  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Lymphopenia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/24 (4.17%)  2/15 (13.33%) 
Metabolic/Laboratory-other  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Neutrophils  1  2/3 (66.67%)  0/3 (0.00%)  4/6 (66.67%)  2/24 (8.33%)  6/15 (40.00%) 
Platelets  1  2/3 (66.67%)  0/3 (0.00%)  5/6 (83.33%)  7/24 (29.17%)  6/15 (40.00%) 
QTc interval  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/24 (0.00%)  1/15 (6.67%) 
Weight loss  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  2/24 (8.33%)  0/15 (0.00%) 
Metabolism and nutrition disorders           
Anorexia  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  4/24 (16.67%)  3/15 (20.00%) 
Bicarbonate  1  0/3 (0.00%)  1/3 (33.33%)  2/6 (33.33%)  1/24 (4.17%)  1/15 (6.67%) 
Dehydration  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Hypercalcemia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Hyperglycemia  1  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Hyperglycemia  1  0/3 (0.00%)  0/3 (0.00%)  3/6 (50.00%)  2/24 (8.33%)  2/15 (13.33%) 
Hyperkalemia  1  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Hypermagnesemia  1  0/3 (0.00%)  0/3 (0.00%)  2/6 (33.33%)  1/24 (4.17%)  1/15 (6.67%) 
Hypocalcemia  1  0/3 (0.00%)  0/3 (0.00%)  2/6 (33.33%)  0/24 (0.00%)  2/15 (13.33%) 
Hypoglycemia  1  0/3 (0.00%)  1/3 (33.33%)  1/6 (16.67%)  0/24 (0.00%)  1/15 (6.67%) 
Hypokalemia  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/24 (4.17%)  0/15 (0.00%) 
Hypomagnesemia  1  0/3 (0.00%)  0/3 (0.00%)  2/6 (33.33%)  3/24 (12.50%)  0/15 (0.00%) 
Hyponatremia  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/24 (0.00%)  1/15 (6.67%) 
Hypophosphatemia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  2/24 (8.33%)  2/15 (13.33%) 
Musculoskeletal and connective tissue disorders           
Extremity-limb, pain  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Joint, pain  1  0/3 (0.00%)  0/3 (0.00%)  2/6 (33.33%)  3/24 (12.50%)  1/15 (6.67%) 
Muscle, pain  1  0/3 (0.00%)  0/3 (0.00%)  2/6 (33.33%)  2/24 (8.33%)  0/15 (0.00%) 
Neck, pain  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/24 (4.17%)  0/15 (0.00%) 
Nonneuropathic generalized weakness  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Nervous system disorders           
CNS, hemorrhage  1  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Dizziness  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Head/headache  1  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%)  2/24 (8.33%)  1/15 (6.67%) 
Leak, CSF  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Speech impairment  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Taste disturbance  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  3/24 (12.50%)  4/15 (26.67%) 
Psychiatric disorders           
Anxiety  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Depression  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/24 (4.17%)  0/15 (0.00%) 
Renal and urinary disorders           
Proteinuria  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/24 (4.17%)  0/15 (0.00%) 
Reproductive system and breast disorders           
Irregular menses  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Cough  1  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Dyspnea  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Nose, hemorrhage  1  0/3 (0.00%)  0/3 (0.00%)  2/6 (33.33%)  4/24 (16.67%)  3/15 (20.00%) 
Pulmonary/Upper Respiratory-other  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/24 (4.17%)  0/15 (0.00%) 
Throat/pharynx/larynx, pain  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Voice changes/dysarthria  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  6/24 (25.00%)  2/15 (13.33%) 
Skin and subcutaneous tissue disorders           
Alopecia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Dry skin  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/24 (4.17%)  0/15 (0.00%) 
Nail changes  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/24 (4.17%)  1/15 (6.67%) 
Petechiae  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Rash: acne/acneiform  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Skin-other  1  0/3 (0.00%)  0/3 (0.00%)  2/6 (33.33%)  2/24 (8.33%)  0/15 (0.00%) 
Vascular disorders           
Hemorrhage-other  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Hypertension  1  1/3 (33.33%)  1/3 (33.33%)  2/6 (33.33%)  4/24 (16.67%)  6/15 (40.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
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
Layout table for Results Point of Contact information
Name/Title: Patrick Y. Wen, MD
Organization: Dana-Farber Cancer Institute
Phone: 617-632-2166
EMail: Patrick_Wen@dfci.harvard.edu
Layout table for additonal information
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
First Submitted: March 9, 2009
First Posted: March 10, 2009
Results First Submitted: March 29, 2016
Results First Posted: November 28, 2016
Last Update Posted: March 14, 2017