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Ph II SAHA and Bevacizumab for Recurrent Malignant Glioma Patients

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: NCT01738646
Recruitment Status : Completed
First Posted : November 30, 2012
Results First Posted : October 29, 2015
Last Update Posted : March 6, 2017
Sponsor:
Collaborators:
Genentech, Inc.
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Duke University

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Recurrent Glioblastoma Multiforme
Malignant Glioma
Adult Brain Tumor
Interventions Drug: Vorinostat
Drug: Bevacizumab
Enrollment 48
Recruitment Details  
Pre-assignment Details 48 participants signed consent. 8 participants are considered screen failures. 40 participants received treatment.
Arm/Group Title Vorinostat & Bevacizumab
Hide Arm/Group Description Patients will be administered bevacizumab every 2 weeks and vorinostat will be taken on days 1-7 and 15-21 of each 28-day cycle at 400 mg per day.
Period Title: Overall Study
Started 40
Completed 38 [1]
Not Completed 2
Reason Not Completed
Still Receiving Treatment             2
[1]
Participants who discontinued study drug for any reason.
Arm/Group Title Vorinostat & Bevacizumab
Hide Arm/Group Description Patients will be administered bevacizumab every 2 weeks and vorinostat will be taken on days 1-7 and 15-21 of each 28-day cycle at 400 mg per day.
Overall Number of Baseline Participants 40
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 40 participants
52.4  (11.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants
Female
16
  40.0%
Male
24
  60.0%
1.Primary Outcome
Title Six-month Progression-free Survival (PFS6)
Hide Description The percentage of participants alive and progression-free at 6 months after the start of study treatment will be determined. Based on Response Assessment in Neuro-Oncology (RANO) criteria, progression is defined as a ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions; significant increase in T2/FLAIR; any new lesion; clear clinical deterioration not attributable to other causes apart from the tumor; failure to return for evaluation as a result of death or deteriorating condition; or clear progression of non-measurable disease. PFS6 will be calculated from the date study treatment started until the date of progression or death, or the date of last follow-up if participants are alive without progression. Kaplan-Meier methods will be used to estimate survival.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat
Arm/Group Title Vorinostat & Bevacizumab
Hide Arm/Group Description:
Patients will be administered bevacizumab every 2 weeks and vorinostat will be taken on days 1-7 and 15-21 of each 28-day cycle at 400 mg per day.
Overall Number of Participants Analyzed 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
30
(16.8 to 44.4)
2.Secondary Outcome
Title Radiographic Response
Hide Description The percentage of participants with a complete or partial response as determined by modified Response Assessment in Neuro-Oncology (RANO) criteria will be determined. Complete Response (CR) is defined as complete disappearance on MR/CT of all enhancing tumor and mass effect, off all corticosteroids (or receiving only adrenal replacement doses) and accompanied by a stable or improving neurologic examination. Partial Response (PR) is defined as greater than or equal to 50% reduction in tumor size on MR/CT by bi-dimensional measurement, on a stable or decreasing dose of corticosteroids and accompanied by a stable or improving neurologic examination. Tumor assessments are done at baseline and the end of every second cycle (every 8 weeks) thereafter.
Time Frame 3 Years
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat
Arm/Group Title Vorinostat & Bevacizumab
Hide Arm/Group Description:

Patients will be administered bevacizumab every 2 weeks and vorinostat will be taken on days 1-7 and 15-21 of each 28-day cycle at 400 mg per day.

Vorinostat

Bevacizumab

Overall Number of Participants Analyzed 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
22.5
(12.1 to 37.7)
3.Secondary Outcome
Title Percentage of Participants Who Experience Grade 3 or Greater, Treatment Related, Non-hematologic Toxicities.
Hide Description The percentage of participants who experience grade 3 or greater, treatment-related, non-hematologic toxicities will be calculated.
Time Frame 2.7 Years
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat
Arm/Group Title Vorinostat & Bevacizumab
Hide Arm/Group Description:
Patients will be administered bevacizumab every 2 weeks and vorinostat will be taken on days 1-7 and 15-21 of each 28-day cycle at 400 mg per day.
Overall Number of Participants Analyzed 40
Measure Type: Number
Unit of Measure: percentage of participants
40
4.Secondary Outcome
Title Median Progression-free Survival (PFS)
Hide Description Progression-free survival is defined as the time in months from the start of protocol treatment until the date of progression or death if death occurred before progression. If the participant is alive and progression-free, PFS will be censored at the date of last follow-up. Kaplan-Meier methods will be used to estimate progression-free survival.
Time Frame 3 Years
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat
Arm/Group Title Vorinostat & Bevacizumab
Hide Arm/Group Description:
Patients will be administered bevacizumab every 2 weeks and vorinostat will be taken on days 1-7 and 15-21 of each 28-day cycle at 400 mg per day.
Overall Number of Participants Analyzed 40
Median (95% Confidence Interval)
Unit of Measure: months
3.7
(2.9 to 4.8)
5.Secondary Outcome
Title Median Overall Survival (OS)
Hide Description Overall survival is defined as the time in months from the start of protocol treatment until the date of death, or the date of last follow-up if alive. Kaplan-Meier methods will be used to estimate overall survival.
Time Frame 3 Years
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat
Arm/Group Title Vorinostat & Bevacizumab
Hide Arm/Group Description:
Patients will be administered bevacizumab every 2 weeks and vorinostat will be taken on days 1-7 and 15-21 of each 28-day cycle at 400 mg per day.
Overall Number of Participants Analyzed 40
Median (95% Confidence Interval)
Unit of Measure: months
10.4
(7.6 to 12.8)
Time Frame From the start of study treatment for a patient until 30 days after treatment is discontinued.
Adverse Event Reporting Description Patients will be evaluated for adverse events (AEs) (all grades), serious AEs, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation in the study.
 
Arm/Group Title Vorinostat & Bevacizumab
Hide Arm/Group Description Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation in the study.
All-Cause Mortality
Vorinostat & Bevacizumab
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
Vorinostat & Bevacizumab
Affected / at Risk (%)
Total   12/40 (30.00%) 
Cardiac disorders   
Sinus bradycardia  1  2/40 (5.00%) 
Gastrointestinal disorders   
Constipation  1  1/40 (2.50%) 
Enterocolitis  1  1/40 (2.50%) 
Nausea  1  1/40 (2.50%) 
General disorders   
Death NOS  1  2/40 (5.00%) 
Fatigue  1  1/40 (2.50%) 
Fever  1  1/40 (2.50%) 
Malaise  1  1/40 (2.50%) 
Infections and infestations   
Lung infection  1  1/40 (2.50%) 
Injury, poisoning and procedural complications   
Fall  1  1/40 (2.50%) 
Musculoskeletal and connective tissue disorders   
Generalized muscle weakness  1  3/40 (7.50%) 
Nervous system disorders   
Edema cerebral  1  1/40 (2.50%) 
Intracranial hemorrhage  1  1/40 (2.50%) 
Pyramidal tract syndrome  1  1/40 (2.50%) 
Seizure  1  7/40 (17.50%) 
Psychiatric disorders   
Confusion  1  1/40 (2.50%) 
Respiratory, thoracic and mediastinal disorders   
Hypoxia  1  1/40 (2.50%) 
Vascular disorders   
Thromboembolic event  1  2/40 (5.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Vorinostat & Bevacizumab
Affected / at Risk (%)
Total   40/40 (100.00%) 
Blood and lymphatic system disorders   
Anemia  1  15/40 (37.50%) 
Cardiac disorders   
Sinus bradycardia  1  5/40 (12.50%) 
Ear and labyrinth disorders   
Ear pain  1  1/40 (2.50%) 
Eye disorders   
Blurred vision  1  3/40 (7.50%) 
Conjunctivitis  1  1/40 (2.50%) 
Gastrointestinal disorders   
Abdominal pain  1  1/40 (2.50%) 
Anal hemorrhage  1  1/40 (2.50%) 
Bloating  1  2/40 (5.00%) 
Constipation  1  11/40 (27.50%) 
Dental caries  1  1/40 (2.50%) 
Diarrhea  1  28/40 (70.00%) 
Dry mouth  1  1/40 (2.50%) 
Dysphagia  1  1/40 (2.50%) 
Gastroesophageal reflux disease  1  1/40 (2.50%) 
Gastrointestinal disorders - Other, specify  1  1/40 (2.50%) 
Mucositis oral  1  3/40 (7.50%) 
Nausea  1  17/40 (42.50%) 
Vomiting  1  6/40 (15.00%) 
General disorders   
Edema limbs  1  1/40 (2.50%) 
Fatigue  1  28/40 (70.00%) 
Pain  1  1/40 (2.50%) 
Infections and infestations   
Bronchial infection  1  1/40 (2.50%) 
Infections and infestations - Other, specify  1  2/40 (5.00%) 
Laryngitis  1  1/40 (2.50%) 
Paronychia  1  1/40 (2.50%) 
Sinusitis  1  4/40 (10.00%) 
Skin infection  1  2/40 (5.00%) 
Upper respiratory infection  1  6/40 (15.00%) 
Urinary tract infection  1  3/40 (7.50%) 
Wound infection  1  1/40 (2.50%) 
Injury, poisoning and procedural complications   
Bruising  1  2/40 (5.00%) 
Fall  1  1/40 (2.50%) 
Investigations   
Alanine aminotransferase increased  1  9/40 (22.50%) 
Alkaline phosphatase increased  1  3/40 (7.50%) 
Aspartate aminotransferase increased  1  9/40 (22.50%) 
Blood bilirubin increased  1  1/40 (2.50%) 
Creatinine increased  1  9/40 (22.50%) 
Lymphocyte count decreased  1  32/40 (80.00%) 
Neutrophil count decreased  1  22/40 (55.00%) 
Platelet count decreased  1  33/40 (82.50%) 
Weight loss  1  2/40 (5.00%) 
White blood cell decreased  1  27/40 (67.50%) 
Metabolism and nutrition disorders   
Anorexia  1  5/40 (12.50%) 
Dehydration  1  1/40 (2.50%) 
Hyperglycemia  1  27/40 (67.50%) 
Hyperkalemia  1  2/40 (5.00%) 
Hypernatremia  1  5/40 (12.50%) 
Hypoalbuminemia  1  1/40 (2.50%) 
Hypocalcemia  1  10/40 (25.00%) 
Hypoglycemia  1  4/40 (10.00%) 
Hypokalemia  1  8/40 (20.00%) 
Hyponatremia  1  11/40 (27.50%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  10/40 (25.00%) 
Back pain  1  3/40 (7.50%) 
Generalized muscle weakness  1  2/40 (5.00%) 
Muscle weakness upper limb  1  1/40 (2.50%) 
Myalgia  1  3/40 (7.50%) 
Pain in extremity  1  1/40 (2.50%) 
Nervous system disorders   
Dizziness  1  2/40 (5.00%) 
Dysgeusia  1  5/40 (12.50%) 
Dysphasia  1  4/40 (10.00%) 
Headache  1  17/40 (42.50%) 
Memory impairment  1  6/40 (15.00%) 
Paresthesia  1  2/40 (5.00%) 
Pyramidal tract syndrome  1  1/40 (2.50%) 
Seizure  1  6/40 (15.00%) 
Tremor  1  3/40 (7.50%) 
Psychiatric disorders   
Agitation  1  1/40 (2.50%) 
Anxiety  1  1/40 (2.50%) 
Delirium  1  1/40 (2.50%) 
Insomnia  1  1/40 (2.50%) 
Renal and urinary disorders   
Proteinuria  1  13/40 (32.50%) 
Renal and urinary disorders - Other, specify  1  2/40 (5.00%) 
Urinary retention  1  2/40 (5.00%) 
Reproductive system and breast disorders   
Dyspareunia  1  1/40 (2.50%) 
Erectile dysfunction  1  1/40 (2.50%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  2/40 (5.00%) 
Epistaxis  1  6/40 (15.00%) 
Hoarseness  1  9/40 (22.50%) 
Nasal congestion  1  1/40 (2.50%) 
Postnasal drip  1  12/40 (30.00%) 
Sleep apnea  1  1/40 (2.50%) 
Skin and subcutaneous tissue disorders   
Alopecia  1  2/40 (5.00%) 
Dry skin  1  9/40 (22.50%) 
Rash acneiform  1  3/40 (7.50%) 
Rash maculo-papular  1  1/40 (2.50%) 
Skin and subcutaneous tissue disorders - Other, specify  1  3/40 (7.50%) 
Vascular disorders   
Hypertension  1  14/40 (35.00%) 
Thromboembolic event  1  3/40 (7.50%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Katherine Peters
Organization: Duke Univeristy Medical Center
Phone: 919 684-3914
EMail: katherine.peters.@dm.duke.edu
Layout table for additonal information
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT01738646    
Other Study ID Numbers: Pro00024983
First Submitted: November 28, 2012
First Posted: November 30, 2012
Results First Submitted: September 30, 2015
Results First Posted: October 29, 2015
Last Update Posted: March 6, 2017