BIBW 2992 (Afatinib) With or Without Daily Temozolomide in the Treatment of Patients With Recurrent Malignant Glioma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00727506
First received: July 31, 2008
Last updated: June 3, 2014
Last verified: January 2014
Results First Received: August 8, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Glioma
Interventions: Drug: BIBW 2992
Drug: TMZ
Drug: BIBW 2992 plus TMZ

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
This study consists of 2 parts (phase I and phase II) with separate participants.

Reporting Groups
  Description
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2 Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2 Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2 Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
Phase II - Temozolomide 75mg/m^2 Patients receiving Temozolomide monotherapy 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
Phase II - Afatinib 40mg Patients receiving Afatinib monotherapy 40mg once daily (q.d.) - Phase II part
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2 Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase II part

Participant Flow:   Overall Study
    Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2     Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2     Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2     Phase II - Temozolomide 75mg/m^2     Phase II - Afatinib 40mg     Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2  
STARTED     6 [1]   8 [1]   18 [1]   39 [2]   41 [2]   39 [2]
COMPLETED     0     0     0     1 [3]   1 [3]   2 [3]
NOT COMPLETED     6     8     18     38     40     37  
Adverse Event                 0                 0                 4                 4                 1                 8  
Dose Limiting Toxicity (DLT)                 2                 0                 2                 0                 0                 0  
Progressive disease                 4                 7                 9                 28                 37                 26  
Refused to continue medication                 0                 1                 2                 2                 1                 2  
Other reason not described above                 0                 0                 1                 4                 1                 1  
[1] Entered
[2] Randomized
[3] On treatment at data cutoff May 12, 2011



  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.
For Phase I part, all patients who were treated with at least one dose of the study medication. For Phase II part, all patients who were randomized and have taken at least one dose of the study medication.

Reporting Groups
  Description
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2 Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2 Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2 Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
Phase II - Temozolomide 75mg/m^2 Patients receiving Temozolomide monotherapy 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
Phase II - Afatinib 40mg Patients receiving Afatinib monotherapy 40mg once daily (q.d.) - Phase II part
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2 Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
Total Total of all reporting groups

Baseline Measures
    Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2     Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2     Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2     Phase II - Temozolomide 75mg/m^2     Phase II - Afatinib 40mg     Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2     Total  
Number of Participants  
[units: participants]
  6     8     18     39     41     39     151  
Age  
[units: years]
Mean ± Standard Deviation
  51.7  ± 12.4     51.6  ± 14.2     51.0  ± 9.4     56.9  ± 10.62     56.6  ± 9.44     55.4  ± 11.02     56.3  ± 10.3  
Gender  
[units: Number of participants]
             
Female     2     2     8     14     14     18     58  
Male     4     6     10     25     27     21     93  
Race/Ethnicity, Customized  
[units: Number of participants]
             
Asian     0     1     0     0     1     1     3  
Black/African American     0     0     2     2     0     2     6  
Hawaiian/Pacific Isle     0     0     0     0     0     1     1  
White     6     7     16     37     40     35     141  
Karnofsky performance score [1]
[units: Number of participants]
             
70     1     1     1     9     9     12     33  
80     1     1     2     13     12     9     38  
90     2     4     11     12     17     15     61  
100     2     2     4     5     3     3     19  
[1] The scale range is from 100 (Normal no complaints) to 0 (dead). This score was used in Phase II randomization stratification and in some efficacy analyses.



  Outcome Measures
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1.  Primary:   Progression-free Survival (PFS-6) at Six Months - Phase II Part   [ Time Frame: At six months after randomization ]

2.  Primary:   Number of Participants With Dose Limiting Toxicities - Phase I Part   [ Time Frame: From randomization till data cut-off (10 Jun 2009), with a mean treatment duration of 51 days ]

3.  Secondary:   Objective Tumor Response (OBR) in Phase II   [ Time Frame: From randomization to until the date of first documented progression or data cutoff on May 12, 2011, whichever came first, with a mean treatment duration of 91 days ]

4.  Secondary:   Objective Tumor Response (OBR) in Phase I   [ Time Frame: From treatment start until the date of first documented progression or data cutoff at May 12, 2011, whichever came first, with a mean treatment duration of 69.7 days. ]


  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 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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim Pharmaceuticals
phone: 1-800-243-0127
e-mail: clintriage.rdg@boehringer-ingelheim.com


No publications provided


Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00727506     History of Changes
Other Study ID Numbers: 1200.36
Study First Received: July 31, 2008
Results First Received: August 8, 2013
Last Updated: June 3, 2014
Health Authority: Canada: Health Canada
United States: Food and Drug Administration