Trial of Continuous Once Daily Oral Treatment Using BIBW 2992 (Afatinib) Plus Sirolimus (Rapamune®) in Patients With Non-small Cell Lung Cancer Harbouring an EGFR Mutation and/or Disease Progression Following Prior Erlotinib or Gefitinib

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00993499
First received: October 8, 2009
Last updated: September 4, 2015
Last verified: September 2015
Results First Received: September 4, 2015  
Study Type: Interventional
Study Design: Endpoint Classification: Safety Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Carcinoma, Non-Small-Cell Lung
Interventions: Drug: BIBW 2992
Drug: Sirolimus (rapamycin)

  Participant Flow
  Hide Participant Flow

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
No text entered.

Reporting Groups
  Description
Afa30+Sir01 Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 1mg tablet once daily.
Afa30+Sir03 Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 3mg tablet once daily.
Afa30+Sir05 Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 5mg tablet once daily.
Afa30+Sir10 Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 10mg tablet once daily.
Afa40+Sir01 Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 1mg tablet once daily.
Afa40+Sir05 Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 5mg tablet once daily.

Participant Flow for 3 periods

Period 1:   Run-in Period (8 Days)
    Afa30+Sir01     Afa30+Sir03     Afa30+Sir05     Afa30+Sir10     Afa40+Sir01     Afa40+Sir05  
STARTED     13     12     10     3     3     3  
COMPLETED     12     9     9     3     3     3  
NOT COMPLETED     1     3     1     0     0     0  
Adverse Event                 0                 1                 0                 0                 0                 0  
Inclusion/exclusion criteria not met                 1                 0                 0                 0                 0                 0  
Consent withdrawn                 0                 1                 0                 0                 0                 0  
Progressive disease                 0                 1                 1                 0                 0                 0  

Period 2:   Discontinued Before Starting Course 3
    Afa30+Sir01     Afa30+Sir03     Afa30+Sir05     Afa30+Sir10     Afa40+Sir01     Afa40+Sir05  
STARTED     12     9     9     3     3     3  
COMPLETED     8     5     6     2     3     3  
NOT COMPLETED     4     4     3     1     0     0  
Progressive Disease                 2                 2                 0                 0                 0                 0  
Withdrawal by Subject                 2                 2                 0                 0                 0                 0  
Dose Limiting Toxicity (DLT)                 0                 0                 1                 1                 0                 0  
Non compliance with the protocol                 0                 0                 2                 0                 0                 0  

Period 3:   Discontinued After Starting Course 3
    Afa30+Sir01     Afa30+Sir03     Afa30+Sir05     Afa30+Sir10     Afa40+Sir01     Afa40+Sir05  
STARTED     12     9     9     3     3     3  
COMPLETED     4     4     3     1     0     0  
NOT COMPLETED     8     5     6     2     3     3  
Withdrawal by Subject                 0                 1                 0                 0                 0                 0  
Progressive Disease                 6                 4                 3                 1                 3                 3  
DLT                 1                 0                 2                 1                 0                 0  
Other adverse event                 1                 0                 1                 0                 0                 0  



  Baseline Characteristics
  Hide Baseline Characteristics

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.
Treated set which included all patients who recieved at least one dose of the trial drug during the first and second treatment counrses.

Reporting Groups
  Description
Afa30+Sir01 Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 1mg tablet once daily.
Afa30+Sir03 Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 3mg tablet once daily.
Afa30+Sir05 Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 5mg tablet once daily.
Afa30+Sir10 Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 10mg tablet once daily.
Afa40+Sir01 Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 1mg tablet once daily.
Afa40+Sir05 Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 5mg tablet once daily.
Total Total of all reporting groups

Baseline Measures
    Afa30+Sir01     Afa30+Sir03     Afa30+Sir05     Afa30+Sir10     Afa40+Sir01     Afa40+Sir05     Total  
Number of Participants  
[units: participants]
  12     9     9     3     3     3     39  
Age  
[units: Years]
Mean (Standard Deviation)
  60.1  (13.6)     56.5  (12.5)     65.1  (9.6)     50.8  (7.5)     53.4  (12.4)     56.5  (17.2)     58.9  (12.3)  
Gender  
[units: Participants]
             
Female     9     6     4     1     2     2     24  
Male     3     3     5     2     1     1     15  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Occurrence of Dose Limiting Toxicities (DLT)   [ Time Frame: 2 first cycles, 56 days ]

2.  Secondary:   Best Overall Response   [ Time Frame: From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days ]

3.  Secondary:   Objective Response   [ Time Frame: From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days ]

4.  Secondary:   Rate of Disease Control   [ Time Frame: From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days ]

5.  Secondary:   Exploratory Examination of EGFR Mutations (Exons 19, 20 and 21 and Others) in Serum/Plasma DNA and Tumour DNA.   [ Time Frame: Multiple time points during the trial ]

6.  Secondary:   Maximum Measured Plasma Concentration of Afatinib at Steady State (Cmax,ss)   [ Time Frame: 24 hours (h), 311h 55minutes (min), 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h and 336h after first administration of afatinib ]

7.  Secondary:   AUC of Afatinib at Steady State Over the Dosing Interval τ (AUCτ,ss)   [ Time Frame: 24 hours (h), 311h 55minutes (min), 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h and 336h after first administration of afatinib ]

8.  Secondary:   Maximum Measured Plasma Concentration of Sirolimus at Steady State (Cmax,ss)   [ Time Frame: 24 hours (h) 5 minutes (min), 24h, 23h, 22h, 20h, 18h, 16h, 5min before first afatinib administration and 144h, 311h 55min, 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h, 336h, 480h after first administration of afatinib ]

9.  Secondary:   AUC of Sirolimus at Steady State Over the Dosing Interval τ (AUCτ,ss)   [ Time Frame: 24 hours (h) 5 minutes (min), 24h, 23h, 22h, 20h, 18h, 16h, 5min before first afatinib administration and 144h, 311h 55min, 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h, 336h, 480h after first administration of afatinib ]

10.  Secondary:   Occurrence of Adverse Events According to CTCAE, Version 3.0   [ Time Frame: From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days ]

11.  Secondary:   Percentage of Patients With Drug-related AEs   [ Time Frame: From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days ]

12.  Secondary:   Frequency of Patients With Possible Clinically-significant Abnormalities in Liver Enzymes or Total Bilirubin   [ Time Frame: From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

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
No text entered.


  More Information
  Hide More Information

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
phone: 1-800-243-0127
e-mail: clintriage.rdg@boehringer-ingelheim.com



Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00993499     History of Changes
Other Study ID Numbers: 1200.70
2009-010432-18 ( EudraCT Number: EudraCT )
Study First Received: October 8, 2009
Results First Received: September 4, 2015
Last Updated: September 4, 2015
Health Authority: Spain: Spanish Agency of Medicines