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Trial of Ponatinib in Patients With Bevacizumab-Refractory Glioblastoma

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ClinicalTrials.gov Identifier: NCT02478164
Recruitment Status : Completed
First Posted : June 23, 2015
Results First Posted : April 2, 2018
Last Update Posted : July 24, 2018
Sponsor:
Information provided by (Responsible Party):
Eudocia Quant Lee, MD, Dana-Farber Cancer Institute

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Glioblastoma
Intervention Drug: Ponatinib
Enrollment 17
Recruitment Details Study began enrolling on 7/13/2015 and enrolled the last participant on 6/13/2017. Enrollment was stopped during a planned interim analysis due to futility. 17 participants were enrolled, but only 15 went on to receive ponatinib study treatment, as 2 participants withdrew after enrolling and before beginning ponatinib.
Pre-assignment Details  
Arm/Group Title Ponatinib
Hide Arm/Group Description Drug will be administered once daily per cycle through oral ingestion.
Period Title: Overall Study
Started 15 [1]
Completed 0
Not Completed 15
Reason Not Completed
Lack of Efficacy             13
Adverse Event             1
Withdrawal by Subject             1
[1]
17 participants enrolled. 15 of 17 received ponatinib as 2 participants withdrew prior to ponatinib.
Arm/Group Title Ponatinib
Hide Arm/Group Description Drug will be administered once daily per cycle through oral ingestion.
Overall Number of Baseline Participants 15
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 15 participants
62
(28 to 75)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
Female
4
  26.7%
Male
11
  73.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
13
  86.7%
Unknown or Not Reported
2
  13.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
American Indian or Alaska Native
0
   0.0%
Asian
1
   6.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
13
  86.7%
More than one race
1
   6.7%
Unknown or Not Reported
0
   0.0%
Initial Glioma Diagnosis  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
Anaplastic Oligodendroglioma
1
   6.7%
Astrocytoma
1
   6.7%
Oligodendroglioma
1
   6.7%
Glioblastoma Multiforme
12
  80.0%
Current Tumor Diagnosis  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
15
 100.0%
Number of Prior Relapses  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
Second relapse
10
  66.7%
Third relapse
4
  26.7%
Fourth relapse
1
   6.7%
First relapse
0
   0.0%
Baseline Karnofsky performance status (KPS)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
100
0
   0.0%
90
4
  26.7%
80
8
  53.3%
70
3
  20.0%
[1]
Measure Description: 'Karnofsky Performance Status' (KPS) scale: 100 = Normal; no complaints; no evidence of disease; 90 = Able to carry on normal activity; minor signs or symptoms of disease; 80 = Normal activity with effort; some sign or symptoms of disease; 70 = Cares for self; unable to carry on normal activity or do active work.
1.Primary Outcome
Title 3-Month Progression-Free Survival (PFS3)
Hide Description PFS3 is the proportion of patients remaining alive and progression-free at 3-months from study entry. Progressive disease was established based on Response Assessment in Neuro-Oncology (RANO) criteria. RANO criteria has 5 potential categories: Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive disease (PD) and Unknown. CR: disappearance of all enhancing lesions, stable or improved non-enhancing lesions, and stable or improved clinically. PR: >= 50% decrease in sum of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, stable or improved non-enhancing lesions, and stable or improved clinically. PD: >25% increase in sum of perpendicular diameters of all measurable enhancing lesions, significant increase of non-enhancing lesions, any new lesions, clear clinical deterioration, failure to return for evaluation due to death or deteriorating condition. SD: does not qualify for CR,PR or PD.
Time Frame 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ponatinib
Hide Arm/Group Description:
Drug will be administered once daily per cycle through oral ingestion.
Overall Number of Participants Analyzed 15
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
2.Secondary Outcome
Title Best Radiographic Response
Hide Description Radiographic response was established based on Response Assessment in Neuro-Oncology (RANO) criteria 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 8 weeks, assessed up to 24 weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ponatinib
Hide Arm/Group Description:
Drug will be administered once daily per cycle through oral ingestion.
Overall Number of Participants Analyzed 15
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Response
0
   0.0%
Partial Response
0
   0.0%
Stable Disease
2
  13.3%
Progressive Disease
10
  66.7%
Unknown
3
  20.0%
3.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS based on Kaplan-Meier is defined as the time from study entry to death or date last known alive.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ponatinib
Hide Arm/Group Description:
Drug will be administered once daily per cycle through oral ingestion.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: days
98
(56 to 257)
4.Secondary Outcome
Title Progression-Free Survival (PFS)
Hide Description PFS based on Kaplan-Meier is defined as the time from study entry to the earliest documentation of disease progression or death. Progressive disease was established based on Response Assessment in Neuro-Oncology (RANO) criteria.
Time Frame 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ponatinib
Hide Arm/Group Description:
Drug will be administered once daily per cycle through oral ingestion.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: days
28
(27 to 30)
Time Frame Assessed each treatment cycle (1 cycle = 28 days) from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 1 (0-3). Assessed an average of 60 days.
Adverse Event Reporting Description Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with ponatinib study treatment-attribution of at least possibly and causing a hospitalization, deemed serious by the treating investigator or grade 5 events per CTCAE v4. Other AEs were defined as events with ponatinib study treatment-attribution of at least possibly and not requiring a hospitalization or deemed non-serious by treating investigator.
 
Arm/Group Title Ponatinib
Hide Arm/Group Description Drug will be administered once daily per cycle through oral ingestion.
All-Cause Mortality
Ponatinib
Affected / at Risk (%)
Total   4/15 (26.67%)    
Show Serious Adverse Events Hide Serious Adverse Events
Ponatinib
Affected / at Risk (%) # Events
Total   2/15 (13.33%)    
Nervous system disorders   
Intracranial hemorrhage  1 [1]  1/15 (6.67%)  1
Skin and subcutaneous tissue disorders   
Bullous dermatitis  1 [2]  1/15 (6.67%)  1
1
Term from vocabulary, CTCAEv4
Indicates events were collected by systematic assessment
[1]
Grade 2
[2]
Grade 3
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Ponatinib
Affected / at Risk (%) # Events
Total   15/15 (100.00%)    
Blood and lymphatic system disorders   
Anemia  1 [1]  1/15 (6.67%)  1
Gastrointestinal disorders   
Abdominal Pain  1 [1]  1/15 (6.67%)  1
Constipation  1 [1]  1/15 (6.67%)  1
Constipation  1 [2]  2/15 (13.33%)  2
Diarrhea  1 [1]  1/15 (6.67%)  1
Gastroesophageal reflux disease  1 [1]  1/15 (6.67%)  1
Mucositis Oral  1 [1]  1/15 (6.67%)  1
Pancreatitis  1 [2]  1/15 (6.67%)  1
Diarrhea  1 [2]  1/15 (6.67%)  1
Nausea  1 [1]  1/15 (6.67%)  1
Constipation  1 [3]  1/15 (6.67%)  1
General disorders   
Fatigue  1 [1]  4/15 (26.67%)  4
Fatigue  1 [2]  2/15 (13.33%)  2
Fatigue  1 [3]  3/15 (20.00%)  3
Investigations   
Alanine aminotransferase increased  1 [1]  3/15 (20.00%)  3
Alkaline phosphatase increased  1 [1]  2/15 (13.33%)  2
Aspartate aminotransferase increased  1 [1]  3/15 (20.00%)  3
CD4 lymphocytes decreased  1 [2]  1/15 (6.67%)  1
GGT increased  1 [1]  2/15 (13.33%)  2
Lipase increased  1 [3]  2/15 (13.33%)  2
Lymphocyte count decreased  1 [3]  1/15 (6.67%)  1
Platelet count decreased  1 [1]  1/15 (6.67%)  1
Platelet count decreased  1 [2]  4/15 (26.67%)  4
Serum amylase increased  1 [1]  1/15 (6.67%)  1
Serum amylase increased  1 [2]  1/15 (6.67%)  1
Alanine aminotransferase increased  1 [3]  1/15 (6.67%)  1
Aspartate aminotransferase increased  1 [3]  1/15 (6.67%)  1
Weight loss  1 [1]  1/15 (6.67%)  1
Metabolism and nutrition disorders   
Anorexia  1 [1]  2/15 (13.33%)  2
Hypoalbuminemia  1 [1]  2/15 (13.33%)  2
Hypocalcemia  1 [1]  2/15 (13.33%)  2
Hyponatremia  1 [1]  1/15 (6.67%)  1
Anorexia  1 [2]  2/15 (13.33%)  2
Other - Mucosal lesions  1 [1]  1/15 (6.67%)  1
Musculoskeletal and connective tissue disorders   
Arthralgia  1 [1]  1/15 (6.67%)  1
Generalized muscle weakness  1 [1]  2/15 (13.33%)  2
Myalgia  1 [1]  1/15 (6.67%)  1
Nervous system disorders   
Dysgeusia  1 [1]  1/15 (6.67%)  1
Skin and subcutaneous tissue disorders   
Dry Skin  1 [1]  1/15 (6.67%)  1
Rash acneiform  1 [2]  1/15 (6.67%)  1
Rash maculo-papular  1 [1]  1/15 (6.67%)  1
Rash maculo-papular  1 [2]  1/15 (6.67%)  1
Other - rash  1 [1]  1/15 (6.67%)  1
Vascular disorders   
Hypertension  1 [2]  2/15 (13.33%)  2
Hypertension  1 [3]  2/15 (13.33%)  2
1
Term from vocabulary, CTCAEv4
Indicates events were collected by systematic assessment
[1]
Grade 1
[2]
Grade 2
[3]
Grade 3
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: Eudocia Q. Lee, MD, MPH
Organization: Dana-Farber Cancer Institute
Phone: 617-632-2166
Responsible Party: Eudocia Quant Lee, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT02478164     History of Changes
Other Study ID Numbers: 15-163
First Submitted: June 12, 2015
First Posted: June 23, 2015
Results First Submitted: March 1, 2018
Results First Posted: April 2, 2018
Last Update Posted: July 24, 2018