Study to Determine the Maximum Tolerated Dose of BIBW 2992 (Afatinib) When Combined With Cisplatin/Paclitaxel or Cisplatin/5-FU in Patients With Advanced Solid Tumours

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00716417
First received: July 15, 2008
Last updated: June 3, 2014
Last verified: August 2013
Results First Received: August 8, 2013  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety Study;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Neoplasms
Intervention: Drug: BIBW 2992

  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
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
Pac175 + Cis50 + Afatinib20 Patients received continous daily dosing with Afatinib 20mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 50mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity.
Pac175 + Cis75 + Afatinib20 Patients received continous daily dosing with Afatinib 20mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity.
Pac175 + Cis75 + Afatinib30 Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity.
Pac175 + Cis75 + Afatinib40 Patients received continous daily dosing with Afatinib 40mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity.
Pac175 + Cis75 + Afatinib50 Patients received continous daily dosing with Afatinib 50mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity.
Cis75 + 5FU750 + Afatinib20 Patients received continous daily dosing with Afatinib 20mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity.
Cis75 + 5FU750 + Afatinib30 Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity.
Cis75 + 5FU750 + Afatinib40 Patients received continous daily dosing with Afatinib 40mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity.
Cis100 + 5FU750 + Afatinib30 Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 100mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity.
Cis100 + 5FU1000 + Afatinib30 Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 1000mg/m^2 and Cisplatin 100mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity.

Participant Flow:   Overall Study
    Pac175 + Cis50 + Afatinib20     Pac175 + Cis75 + Afatinib20     Pac175 + Cis75 + Afatinib30     Pac175 + Cis75 + Afatinib40     Pac175 + Cis75 + Afatinib50     Cis75 + 5FU750 + Afatinib20     Cis75 + 5FU750 + Afatinib30     Cis75 + 5FU750 + Afatinib40     Cis100 + 5FU750 + Afatinib30     Cis100 + 5FU1000 + Afatinib30  
STARTED     3     6     5     11     1     3     7     3     5     3  
COMPLETED     0     0     0     0     0     0     0     0     0     0  
NOT COMPLETED     3     6     5     11     1     3     7     3     5     3  
Adverse Event                 0                 0                 2                 1                 0                 0                 3                 1                 0                 3  
Withdrawal by Subject                 0                 1                 0                 2                 0                 0                 1                 0                 0                 0  
Progressive disease                 3                 5                 3                 8                 0                 3                 3                 1                 5                 0  
Dose limiting toxicity (DLT)                 0                 0                 0                 0                 1                 0                 0                 0                 0                 0  
On patient request due to toxicities                 0                 0                 0                 0                 0                 0                 0                 1                 0                 0  



  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.
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Reporting Groups
  Description
Pac175 + Cis50 + Afatinib20 Patients received continous daily dosing with Afatinib 20mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 50mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity.
Pac175 + Cis75 + Afatinib20 Patients received continous daily dosing with Afatinib 20mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity.
Pac175 + Cis75 + Afatinib30 Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity.
Pac175 + Cis75 + Afatinib40 Patients received continous daily dosing with Afatinib 40mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity.
Pac175 + Cis75 + Afatinib50 Patients received continous daily dosing with Afatinib 50mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity.
Cis75 + 5FU750 + Afatinib20 Patients received continous daily dosing with Afatinib 20mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity.
Cis75 + 5FU750 + Afatinib30 Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity.
Cis75 + 5FU750 + Afatinib40 Patients received continous daily dosing with Afatinib 40mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity.
Cis100 + 5FU750 + Afatinib30 Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 100mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity.
Cis100 + 5FU1000 + Afatinib30 Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 1000mg/m^2 and Cisplatin 100mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity.
Total Total of all reporting groups

Baseline Measures
    Pac175 + Cis50 + Afatinib20     Pac175 + Cis75 + Afatinib20     Pac175 + Cis75 + Afatinib30     Pac175 + Cis75 + Afatinib40     Pac175 + Cis75 + Afatinib50     Cis75 + 5FU750 + Afatinib20     Cis75 + 5FU750 + Afatinib30     Cis75 + 5FU750 + Afatinib40     Cis100 + 5FU750 + Afatinib30     Cis100 + 5FU1000 + Afatinib30     Total  
Number of Participants  
[units: participants]
  3     6     5     11     1     3     7     3     5     3     47  
Age  
[units: years]
Mean ± Standard Deviation
  56.7  ± 14.0     61.8  ± 15.6     61.8  ± 5.9     58.1  ± 7.8     54.0  ± NA [1]   52.7  ± 9.7     53.1  ± 16.1     65.0  ± 8.5     59.2  ± 14.4     63.7  ± 9.3     58.58  ± 11.3  
Gender  
[units: Number¬†of¬†participants]
                     
Female     3     3     2     3     0     0     2     2     3     1     19  
Male     0     3     3     8     1     3     5     1     2     2     28  
[1] only one patient in this group



  Outcome Measures
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1.  Primary:   Number of Participants With Dose Limiting Toxicities (DLT) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)   [ Time Frame: 21 days ]

2.  Primary:   Maximum Tolerated Dose (MTD) for Regimen A and Regimen B   [ Time Frame: 21 days ]

3.  Secondary:   Number of Patients With Objective Response   [ Time Frame: Tumor assessment were performed at screening and every 2nd cycle until end of follow up (=end of treatment + 30 days +/- 7 days) ]

4.  Secondary:   Maximum Concentration of Afatinib in Plasma at Steady State (Cmax,ss)   [ Time Frame: 0.05hours (h) before administration and 1h, 2h, 2h 55 minutes (min), 4h, 4h 30min, 5h, 6h, 8h, 10h, 24h, 48h, 216h, 480h after administration ]


  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: NCT00716417     History of Changes
Other Study ID Numbers: 1200.37, 2008-002613-43
Study First Received: July 15, 2008
Results First Received: August 8, 2013
Last Updated: June 3, 2014
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP