Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

BIBF 1120 for Recurrent High-Grade Gliomas

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: NCT01380782
Recruitment Status : Completed
First Posted : June 27, 2011
Results First Posted : August 18, 2014
Last Update Posted : August 18, 2014
Sponsor:
Collaborators:
Boehringer Ingelheim
Wake Forest University Health Sciences
University of Virginia
Massachusetts General Hospital
The Cleveland Clinic
Information provided by (Responsible Party):
Patrick Y. Wen, MD, Dana-Farber Cancer Institute

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Glioblastoma
Gliosarcoma
Anaplastic Astrocytoma
Anaplastic Oligodendroglioma
Anaplastic Oligoastrocytoma
Intervention Drug: BIBF 1120
Enrollment 37
Recruitment Details Study activated at Dana-Farber Cancer Institute in May 2012 and was eventually activated at Massachusetts General Hospital, Cleveland Clinic, and University of Virginia. The bevacizumab-treated arm closed to accrual in December 2012 and the bevacizumab-naive arm closed in March 2013, both due to futility.
Pre-assignment Details  
Arm/Group Title Arm A (Bevacizumab-naive) - GBM Arm A (Bevacizumab-naive) - AG Arm B (Bevacizumab Treated) - GBM Arm B (Bevacizumab Treated) - AG
Hide Arm/Group Description Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was glioblastoma (GBM). Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was anaplastic glioma (AG). Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was glioblastoma (GBM). Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was anaplastic glioma (AG).
Period Title: Overall Study
Started 12 10 11 4
Completed 0 0 0 0
Not Completed 12 10 11 4
Reason Not Completed
Adverse Event             0             1             0             0
Death             1             0             0             0
Lack of Efficacy             10             9             10             3
Physician Decision             1             0             0             0
Withdrawal by Subject             0             0             1             1
Arm/Group Title Arm A Bevacizumab-naive Arm B Bevacizumab-treated Total
Hide Arm/Group Description Bevacizumab-naive participants Bevacizumab-treated participants Total of all reporting groups
Overall Number of Baseline Participants 22 14 36
Hide Baseline Analysis Population Description
One participant from Arm B (GBM) was removed from analysis, aside from the review of adverse events, due to later determining she did not meet eligibility requirements as a result of prior stereotatic radiosurgery received prior to starting the study.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 22 participants 14 participants 36 participants
54
(28 to 75)
52
(32 to 70)
52
(28 to 75)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 14 participants 36 participants
Female
15
  68.2%
3
  21.4%
18
  50.0%
Male
7
  31.8%
11
  78.6%
18
  50.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 14 participants 36 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   4.5%
0
   0.0%
1
   2.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
19
  86.4%
11
  78.6%
30
  83.3%
More than one race
1
   4.5%
0
   0.0%
1
   2.8%
Unknown or Not Reported
1
   4.5%
3
  21.4%
4
  11.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 14 participants 36 participants
Hispanic or Latino
0
   0.0%
1
   7.1%
1
   2.8%
Not Hispanic or Latino
21
  95.5%
12
  85.7%
33
  91.7%
Unknown or Not Reported
1
   4.5%
1
   7.1%
2
   5.6%
Karnofsky Performance Status   [1] 
Median (Full Range)
Unit of measure:  Units on a scale
Number Analyzed 22 participants 14 participants 36 participants
90
(60 to 100)
90
(60 to 100)
90
(60 to 100)
[1]
Measure Description: Karnofsky Performance Status ranges from 0 (Dead) to 100 (Normal, no complaints, no evidence of disease) in increments of 10. This was measured at baseline, prior to any treatment on study.
1.Primary Outcome
Title 6-Month Progression Free Survival
Hide Description To determine the efficacy of BIBF 1120 in bevacizumab-naive participants with recurrent glioblastoma (GBM) as measured by 6-month progression-free survival (PFS6).
Time Frame Six months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm A (Bevacizumab-naive) - GBM
Hide Arm/Group Description:
Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was glioblastoma (GBM).
Overall Number of Participants Analyzed 12
Measure Type: Number
Unit of Measure: percentage of participants
0
2.Primary Outcome
Title 3-Month Progression Free Survival
Hide Description To determine the efficacy of BIBF 1120 in bevacizumab-treated participants with recurrent GBM as measured by 3-month progression free survival (PFS3).
Time Frame 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm B (Bevacizumab Treated) - GBM
Hide Arm/Group Description:
Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was glioblastoma (GBM).
Overall Number of Participants Analyzed 10
Measure Type: Number
Unit of Measure: percentage of participants
0
3.Secondary Outcome
Title Proportion of Participants Experiencing Stable Disease (SD) as Their Best Radiographic Response
Hide Description Best radiographic response in both populations. There were no participants with partial or complete responses, so the results are being reported in the proportion of participants who experienced stable disease (SD) as their best response (as opposed to progressive disease).
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm A (Bevacizumab-naive) - GBM Arm A (Bevacizumab-naive) - AG Arm B (Bevacizumab Treated) - GBM Arm B (Bevacizumab Treated) - AG
Hide Arm/Group Description:
Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was glioblastoma (GBM).
Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was anaplastic glioma (AG).
Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was glioblastoma (GBM).
Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was anaplastic glioma (AG).
Overall Number of Participants Analyzed 12 10 10 4
Measure Type: Number
Unit of Measure: % of patients with best response SD
33 40 10 25
4.Secondary Outcome
Title Overall Survival
Hide Description Overall survival in both populations
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm A (Bevacizumab-naive) - GBM Arm A (Bevacizumab-naive) - AG Arm B (Bevacizumab Treated) - GBM Arm B (Bevacizumab Treated) - AG
Hide Arm/Group Description:
Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was glioblastoma (GBM).
Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was anaplastic glioma (AG).
Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was glioblastoma (GBM).
Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was anaplastic glioma (AG).
Overall Number of Participants Analyzed 12 10 10 4
Median (95% Confidence Interval)
Unit of Measure: months
6.9
(3.7 to 8.1)
11.3
(2.7 to 14.6)
2.6
(1.0 to 6.9)
7.3
(1.4 to 18.1)
5.Secondary Outcome
Title Time-to-tumor Progression
Hide Description Time-to-tumor progression in both populations.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm A (Bevacizumab-naive) - GBM Arm A (Bevacizumab-naive) - AG Arm B (Bevacizumab Treated) - GBM Arm B (Bevacizumab Treated) - AG
Hide Arm/Group Description:
Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was glioblastoma (GBM).
Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was anaplastic glioma (AG).
Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was glioblastoma (GBM).
Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was anaplastic glioma (AG).
Overall Number of Participants Analyzed 12 10 10 4
Median (95% Confidence Interval)
Unit of Measure: days
28
(27 to 83)
28
(27 to 138)
28
(22 to 28)
36
(27 to 55)
6.Secondary Outcome
Title Safety Profile as Summarized With Descriptive Statistics (Using Toxicity Data Gathered on Trial)
Hide Description Safety profile in both populations - as adverse events are posted separately in detail, these results will demonstrate serious adverse events (defined as grades 3-5) that were judged at least possibly related to Nintedanib (BIBF 1120).
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title All Participants (Arm A and B)
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 37
Measure Type: Number
Unit of Measure: number of incidents
Abdominal pain 1
Reversible transaminase elevation 8
Hypertension 1
Hypophosphatemia 3
Intracranial hemorrhage 1
Colonic perforation 2
Pulmonary embolism 1
7.Other Pre-specified Outcome
Title Exploratory Objective #1: Progression-free Survival at 3- and 6-months for Participants With Recurrent Anaplastic Gliomas (AG)
Hide Description To explore the efficacy of BIBF 1120 in bevacizumab-naïve and bevacizumab-treated participants with recurrent anaplastic gliomas (AG) survival was assessed at 6 months for Arm A and 3 months for Arm B.
Time Frame Arm A - 6 months; Arm B - 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm A (Bevacizumab-naive) - AG Arm B (Bevacizumab Treated) - AG
Hide Arm/Group Description:
Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was anaplastic glioma (AG).
Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was anaplastic glioma (AG).
Overall Number of Participants Analyzed 10 4
Measure Type: Number
Unit of Measure: percentage of participants
0 0
8.Other Pre-specified Outcome
Title Exploratory Objective #2: Determination if Any Correlation Exists Between Patient Outcomes (Survival, PFS3, PFS6) and Tumor Genotype and/or Expression Profile
Hide Description To explore the extent to which the tumor's genotype and expression profile correlate with outcome.
Time Frame 2 years
Outcome Measure Data Not Reported
9.Other Pre-specified Outcome
Title Exploratory Objective #3: Determination if Any Correlation Exists Between Patient Outcomes (Survival, PFS3, PFS6) and Serum Angiogenic Peptides, Circulating Endothelial Cells, and/or Circulating Progenitor Cells
Hide Description To explore the correlation between serum angiogenic peptides, circulating endothelial cells, and circulating progenitor cells with response to therapy.
Time Frame 2 years
Outcome Measure Data Not Reported
10.Other Pre-specified Outcome
Title Exploratory Objective #4: Determination if Any Correlation Exists Between Patient Outcomes (Survival, PFS3, PFS6) and Perfusion MRI, Diffusion MRI
Hide Description To explore the correlation between perfusion MRI, diffusion MRI and response to therapy.
Time Frame 2 years
Outcome Measure Data Not Reported
Time Frame Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug.
Adverse Event Reporting Description Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.
 
Arm/Group Title Arm A Arm B
Hide Arm/Group Description Bevacizumab-naive participants Bevacizumab-treated participants
All-Cause Mortality
Arm A Arm B
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Arm A Arm B
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/22 (36.36%)      5/14 (35.71%)    
Gastrointestinal disorders     
Abdominal pain * 1 [1]  0/22 (0.00%)  0 1/14 (7.14%)  1
Colonic perforation * 1 [2]  1/22 (4.55%)  2 0/14 (0.00%)  0
Enterocolitis * 1 [3]  0/22 (0.00%)  0 1/14 (7.14%)  2
General disorders     
Death NOS * 1 [4]  1/22 (4.55%)  1 2/14 (14.29%)  2
Investigations     
Alanine aminotransferase increased * 1 [5]  0/22 (0.00%)  0 1/14 (7.14%)  1
Aspartate aminotransferase increased * 1 [5]  0/22 (0.00%)  0 1/14 (7.14%)  1
Musculoskeletal and connective tissue disorders     
Muscle weakness left-sided * 1 [6]  0/22 (0.00%)  0 1/14 (7.14%)  1
Muscle weakness right-sided * 1 [7]  1/22 (4.55%)  1 0/14 (0.00%)  0
Nervous system disorders     
Dysphasia * 1 [7]  1/22 (4.55%)  1 0/14 (0.00%)  0
Edema cerebral * 1 [8]  1/22 (4.55%)  1 1/14 (7.14%)  1
Hydrocephalus * 1 [9]  0/22 (0.00%)  0 1/14 (7.14%)  1
Intracranial hemorrhage * 1 [10]  1/22 (4.55%)  2 0/14 (0.00%)  0
Psychiatric disorders     
Agitation * 1 [11]  1/22 (4.55%)  1 0/14 (0.00%)  0
Delirium * 1 [12]  1/22 (4.55%)  1 0/14 (0.00%)  0
Depression * 1 [11]  1/22 (4.55%)  1 0/14 (0.00%)  0
Suicidal ideation * 1 [13]  1/22 (4.55%)  2 0/14 (0.00%)  0
Suicidal attempt * 1 [9]  1/22 (4.55%)  1 0/14 (0.00%)  0
Vascular disorders     
Thromboembolic event * 1 [14]  1/22 (4.55%)  1 1/14 (7.14%)  1
Vascular disorders - Other * 1 [15]  0/22 (0.00%)  0 1/14 (7.14%)  2
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (4.0)
[1]
Grade 3 possibly related to BIBF 1120, expected
[2]
Same participant - grade 4, possibly related to BIBF 1120 and unexpected; grade 5, possibly related to BIBF 1120 and expected.
[3]
Grade 3, unrelated to BIBF 1120, unexpected Grade 5, unrelated to BIBF 1120, unexpected
[4]
Arm A - grade 5, unrelated, unexpected Arm B - both events grade 5, unrelated, unexpected
[5]
Grade 3, possibly related to BIBF 1120, expected
[6]
Grade 2, unrelated to BIBF 1120, unexpected
[7]
Grade 2, possibly related to BIBF 1120, unexpected
[8]
Arm A - grade 4, unlikely related to BIBF 1120, unexpected Arm B - grade <4, unrelated to BIBF 1120, unexpected
[9]
Grade 3, unrelated to BIBF 1120, unexpected
[10]
Same participant - grade 2 and grade 3, possibly related to BIBF 1120, unexpected
[11]
Grade 4, unrelated to BIBF 1120, unexpected
[12]
Grade 3, unlikely related to BIBF 1120, unexpected
[13]
Same participant - grade 2 twice, unrelated to BIBF 1120, and unexpected
[14]
Arm A - grade 5, possibly related to BIBF 1120, unexpected Arm B - grade 3, unlikely related to BIBF 1120, unexpected
[15]
Both grade 4, one unlikely related and other unrelated to BIBF 1120, both unexpected
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm A Arm B
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   22/22 (100.00%)      14/14 (100.00%)    
Cardiac disorders     
Cardiac disorders - Other * 1  0/22 (0.00%)  0 1/14 (7.14%)  1
Sinus bradycardia * 1  0/22 (0.00%)  0 1/14 (7.14%)  1
Sinus tachycardia * 1  0/22 (0.00%)  0 1/14 (7.14%)  1
Endocrine disorders     
Cushingoid * 1  0/22 (0.00%)  0 1/14 (7.14%)  1
Eye disorders     
Eye disorders - Other * 1  1/22 (4.55%)  1 1/14 (7.14%)  1
Gastrointestinal disorders     
Abdominal pain * 1  3/22 (13.64%)  3 1/14 (7.14%)  1
Constipation * 1  2/22 (9.09%)  2 1/14 (7.14%)  1
Diarrhea * 1  7/22 (31.82%)  9 4/14 (28.57%)  4
Nausea * 1  3/22 (13.64%)  5 4/14 (28.57%)  5
Vomiting * 1  5/22 (22.73%)  5 3/14 (21.43%)  3
Duodenal hemorrhage * 1  0/22 (0.00%)  0 1/14 (7.14%)  1
General disorders     
Edema limbs * 1  2/22 (9.09%)  2 0/14 (0.00%)  0
Fatigue * 1  4/22 (18.18%)  4 8/14 (57.14%)  10
Pain * 1  1/22 (4.55%)  1 1/14 (7.14%)  1
Infusion site extravasation * 1  0/22 (0.00%)  0 1/14 (7.14%)  1
Infections and infestations     
Urinary tract infection * 1  4/22 (18.18%)  4 1/14 (7.14%)  1
Lung infection * 1  0/22 (0.00%)  0 1/14 (7.14%)  1
Injury, poisoning and procedural complications     
Fall * 1  2/22 (9.09%)  2 2/14 (14.29%)  3
Investigations     
Alanine aminotransferase increased * 1  4/22 (18.18%)  10 3/14 (21.43%)  4
Aspartate aminotransferase increased * 1  4/22 (18.18%)  9 0/14 (0.00%)  0
Platelet count decreased * 1  2/22 (9.09%)  2 3/14 (21.43%)  5
Weight loss * 1  2/22 (9.09%)  4 0/14 (0.00%)  0
White blood cell decreased * 1  2/22 (9.09%)  2 0/14 (0.00%)  0
Activated partial thromboplastic time prolonged * 1  0/22 (0.00%)  0 1/14 (7.14%)  1
INR increased * 1  0/22 (0.00%)  0 1/14 (7.14%)  1
Metabolism and nutrition disorders     
Anorexia * 1  2/22 (9.09%)  3 1/14 (7.14%)  1
Hypokalemia * 1  1/22 (4.55%)  1 1/14 (7.14%)  1
Hypomagnesemia * 1  1/22 (4.55%)  1 1/14 (7.14%)  1
Hypophosphatemia * 1  4/22 (18.18%)  6 0/14 (0.00%)  0
Hyperglycemia * 1  0/22 (0.00%)  0 2/14 (14.29%)  3
Hypocalcemia * 1  0/22 (0.00%)  0 1/14 (7.14%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  0/22 (0.00%)  0 1/14 (7.14%)  1
Bone pain * 1  0/22 (0.00%)  0 2/14 (14.29%)  2
Generalized muscle weakness * 1  0/22 (0.00%)  0 2/14 (14.29%)  2
Muscle weakness left-sided * 1  0/22 (0.00%)  0 1/14 (7.14%)  1
Muscle weakness lower limb * 1  0/22 (0.00%)  0 1/14 (7.14%)  1
Muscle weakness right-sided * 1  0/22 (0.00%)  0 1/14 (7.14%)  1
Pain in extremity * 1  0/22 (0.00%)  0 2/14 (14.29%)  2
Nervous system disorders     
Dysarthria * 1  2/22 (9.09%)  2 0/14 (0.00%)  0
Headache * 1  4/22 (18.18%)  4 2/14 (14.29%)  2
Seizure * 1  2/22 (9.09%)  2 3/14 (21.43%)  4
Ataxia * 1  0/22 (0.00%)  0 1/14 (7.14%)  1
Concentration impairment * 1  0/22 (0.00%)  0 1/14 (7.14%)  1
Dysphasia * 1  0/22 (0.00%)  0 3/14 (21.43%)  3
Encephalopathy * 1  0/22 (0.00%)  0 1/14 (7.14%)  1
Paresthesia * 1  0/22 (0.00%)  0 1/14 (7.14%)  1
Peripheral motor neuropathy * 1  0/22 (0.00%)  0 1/14 (7.14%)  1
Psychiatric disorders     
Agitation * 1  1/22 (4.55%)  1 1/14 (7.14%)  1
Confusion * 1  2/22 (9.09%)  3 3/14 (21.43%)  3
Depression * 1  1/22 (4.55%)  1 1/14 (7.14%)  1
Personality change * 1  2/22 (9.09%)  2 0/14 (0.00%)  0
Anxiety * 1  0/22 (0.00%)  0 1/14 (7.14%)  1
Delirium * 1  0/22 (0.00%)  0 1/14 (7.14%)  1
Insomnia * 1  0/22 (0.00%)  0 2/14 (14.29%)  2
Renal and urinary disorders     
Urinary incontinence * 1  0/22 (0.00%)  0 1/14 (7.14%)  1
Reproductive system and breast disorders     
Vaginal hemorrhage * 1  0/22 (0.00%)  0 1/14 (7.14%)  1
Respiratory, thoracic and mediastinal disorders     
Epistaxis * 1  0/22 (0.00%)  0 1/14 (7.14%)  1
Hoarseness * 1  0/22 (0.00%)  0 1/14 (7.14%)  1
Respiratory failure * 1  0/22 (0.00%)  0 1/14 (7.14%)  1
Respiratory, thoracic and mediastinal disorders - Other * 1  0/22 (0.00%)  0 1/14 (7.14%)  1
Skin and subcutaneous tissue disorders     
Rash maculo-papular * 1  2/22 (9.09%)  2 0/14 (0.00%)  0
Purpura * 1  0/22 (0.00%)  0 1/14 (7.14%)  1
Vascular disorders     
Hypertension * 1  5/22 (22.73%)  6 6/14 (42.86%)  7
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (4.0)
The trial intended to enroll 14 participants onto Arm A GBM, but only 10 enrolled due to futility. In addition, 10 AG participants were to be enrolled onto each Arm as exploratory cohorts, but again due to futility only 4 enrolled onto Arm B.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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: 6176322166
Responsible Party: Patrick Y. Wen, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01380782     History of Changes
Other Study ID Numbers: 11-055
BIBF 1199.94 ( Other Identifier: Boehringer-Ingleheim )
First Submitted: June 21, 2011
First Posted: June 27, 2011
Results First Submitted: July 14, 2014
Results First Posted: August 18, 2014
Last Update Posted: August 18, 2014