Phase I Dose Escalation Study of Concomitant BIBF 1120 and BIBW 2992 in Patients With Advanced Solid Tumours.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00998296
First received: October 19, 2009
Last updated: July 23, 2015
Last verified: July 2015
Results First Received: November 14, 2014  
Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Neoplasms
Interventions: Drug: BIBW 2992
Drug: BIBF 1120

  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
Trial consisted of a dose-escalation phase (to determine the maximum tolerated dose (MTD) of treatments administered concomitantly) and an expansion phase(to assess the safety and the preliminary anti-tumour activity of the combination therapy at the previously determined MTD in patients with non-small cell lung cancer or pancreatic adenocarcinoma)

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
Nintedanib 150 mg +Afatinib 30 mg - Continuously

Patients receiving oral administration of soft-gelatine capsule of Nintedanib 150 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 30 mg was given continuously once daily (q.d.).

This is a part of the "dose-escalation phase".

Nintedanib 150 mg +Afatinib 40 mg - Continuously

Patients receiving oral administration of soft-gelatine capsule of Nintedanib 150 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 40 mg was given continuously once daily (q.d.).

This is a part of the "dose-escalation phase".

Nintedanib 200 mg +Afatinib 10 mg - Continuously

Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 10 mg was given continuously once daily (q.d.).

This is a part of the "dose-escalation phase".

Nintedanib 200 mg +Afatinib 20 mg - Continuously

Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 20 mg was given continuously once daily (q.d.).

This is a part of the "dose-escalation phase".

Nintedanib 200 mg +Afatinib 30 mg - Continuously

Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 30 mg was given continuously once daily (q.d.).

This is a part of the "dose-escalation phase".

Nintedanib 200 mg +Afatinib 40 mg - Continuously

Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 40 mg was given continuously once daily (q.d.).

This is a part of the "dose-escalation phase".

Nintedanib 150 mg +Afatinib 40 mg - Intermittently

Patients receiving oral administration of soft-gelatine capsule of Nintedanib 150 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 40 mg was given intermittently once daily (q.d.) every other week.

This is a part of the "dose-escalation phase".

Nintedanib 200 mg +Afatinib 30 mg - Intermittently

Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 30 mg was given intermittently once daily (q.d.) every other week.

This is a part of the "dose-escalation phase".

Nintedanib 200 mg +Afatinib 40 mg - Intermittently

Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 40 mg was given intermittently once daily (q.d.) every other week.

This is a part of the "dose-escalation phase".

NSCLC

Patients with non-small cell lung cancer (NSCLC) receiving the study drug combination at the maximum tolerated dose (MTD) level determined for continuous afatinib and nintedanib dosing during the dose-escalation phase (oral administration of soft-gelatine capsule of Nintedanib 150 mg (b.i.d.) plus film-coated tablet of Afatinib 30 mg (q.d.)).

This is a part of the "expansion phase" which follows on the dose-escalation phase.

Pancreatic Adenocarcinoma

Patients with Pancreatic adenocarcinoma were to be treated with the study drug combination at the maximum tolerated dose (MTD) level determined for continuous afatinib and nintedanib dosing during the dose-escalation phase (oral administration of soft-gelatine capsule of Nintedanib 150 mg bid plus film-coated tablet of Afatinib 30 mg qd).

This is a part of the "expansion phase" which follows on the dose-escalation phase.


Participant Flow:   Overall Study
    Nintedanib 150 mg +Afatinib 30 mg - Continuously     Nintedanib 150 mg +Afatinib 40 mg - Continuously     Nintedanib 200 mg +Afatinib 10 mg - Continuously     Nintedanib 200 mg +Afatinib 20 mg - Continuously     Nintedanib 200 mg +Afatinib 30 mg - Continuously     Nintedanib 200 mg +Afatinib 40 mg - Continuously     Nintedanib 150 mg +Afatinib 40 mg - Intermittently     Nintedanib 200 mg +Afatinib 30 mg - Intermittently     Nintedanib 200 mg +Afatinib 40 mg - Intermittently     NSCLC     Pancreatic Adenocarcinoma  
STARTED     6     3     3     3     8     3     7     6     6     18     7  
COMPLETED     6 [1]   2 [1]   3 [1]   3 [1]   6 [1]   3 [1]   6 [1]   4 [1]   4 [1]   0     0  
NOT COMPLETED     0     1     0     0     2     0     1     2     2     18     7  
Progressive disease                 0                 1                 0                 0                 0                 0                 1                 0                 0                 14                 5  
Dose limiting or dose reducing toxicity                 0                 0                 0                 0                 1                 0                 0                 2                 2                 0                 0  
Other adverse event                 0                 0                 0                 0                 1                 0                 0                 0                 0                 1                 2  
Refused to continue taking trial med.                 0                 0                 0                 0                 0                 0                 0                 0                 0                 2                 0  
Reason other than those specified above                 0                 0                 0                 0                 0                 0                 0                 0                 0                 1                 0  
[1] Did not discontinue treatment before or at Day 28



  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 (TS): A treated set (TS) was defined consisting of all patients who received at least one dose of nintedanib or afatinib during the study period.

Reporting Groups
  Description
Nintedanib 150 mg +Afatinib 30 mg - Continuously

Patients receiving oral administration of soft-gelatine capsule of Nintedanib 150 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 30 mg was given continuously once daily (q.d.).

This is a part of the "dose-escalation phase".

Nintedanib 150 mg +Afatinib 40 mg - Continuously

Patients receiving oral administration of soft-gelatine capsule of Nintedanib 150 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 40 mg was given continuously once daily (q.d.).

This is a part of the "dose-escalation phase".

Nintedanib 200 mg +Afatinib 10 mg - Continuously

Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 10 mg was given continuously once daily (q.d.).

This is a part of the "dose-escalation phase".

Nintedanib 200 mg +Afatinib 20 mg - Continuously

Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 20 mg was given continuously once daily (q.d.).

This is a part of the "dose-escalation phase".

Nintedanib 200 mg +Afatinib 30 mg - Continuously

Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 30 mg was given continuously once daily (q.d.).

This is a part of the "dose-escalation phase".

Nintedanib 200 mg +Afatinib 40 mg - Continuously

Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 40 mg was given continuously once daily (q.d.).

This is a part of the "dose-escalation phase".

Nintedanib 150 mg +Afatinib 40 mg - Intermittently

Patients receiving oral administration of soft-gelatine capsule of Nintedanib 150 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 40 mg was given intermittently once daily (q.d.) every other week.

This is a part of the "dose-escalation phase".

Nintedanib 200 mg +Afatinib 30 mg - Intermittently

Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 30 mg was given intermittently once daily (q.d.) every other week.

This is a part of the "dose-escalation phase".

Nintedanib 200 mg +Afatinib 40 mg - Intermittently

Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 40 mg was given intermittently once daily (q.d.) every other week.

This is a part of the "dose-escalation phase".

NSCLC

Patients with non-small cell lung cancer (NSCLC) receiving the study drug combination at the maximum tolerated dose (MTD) level determined for continuous afatinib and nintedanib dosing during the dose-escalation phase (oral administration of soft-gelatine capsule of Nintedanib 150 mg (b.i.d.) plus film-coated tablet of Afatinib 30 mg (q.d.)).

This is a part of the "expansion phase" which follows on the dose-escalation phase.

Pancreatic Adenocarcinoma

Patients with Pancreatic adenocarcinoma were to be treated with the study drug combination at the maximum tolerated dose (MTD) level determined for continuous afatinib and nintedanib dosing during the dose-escalation phase (oral administration of soft-gelatine capsule of Nintedanib 150 mg bid plus film-coated tablet of Afatinib 30 mg qd).

This is a part of the "expansion phase" which follows on the dose-escalation phase.

Total Total of all reporting groups

Baseline Measures
    Nintedanib 150 mg +Afatinib 30 mg - Continuously     Nintedanib 150 mg +Afatinib 40 mg - Continuously     Nintedanib 200 mg +Afatinib 10 mg - Continuously     Nintedanib 200 mg +Afatinib 20 mg - Continuously     Nintedanib 200 mg +Afatinib 30 mg - Continuously     Nintedanib 200 mg +Afatinib 40 mg - Continuously     Nintedanib 150 mg +Afatinib 40 mg - Intermittently     Nintedanib 200 mg +Afatinib 30 mg - Intermittently     Nintedanib 200 mg +Afatinib 40 mg - Intermittently     NSCLC     Pancreatic Adenocarcinoma     Total  
Number of Participants  
[units: participants]
  6     3     3     3     8     3     7     6     6     18     7     70  
Age  
[units: years]
Mean (Standard Deviation)
  53.7  (8.1)     51.7  (1.5)     46.7  (4.9)     53.3  (11.0)     51.5  (9.7)     44.3  (8.1)     64.9  (3.5)     52.2  (6.0)     63.3  (10.3)     58.1  (10.9)     58.1  (6.8)     56.0  (9.7)  
Gender  
[units: participants]
                       
Female     3     1     0     1     6     2     0     4     2     11     1     31  
Male     3     2     3     2     2     1     7     2     4     7     6     39  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Maximum Tolerated Dose (MTD) of Nintedanib and Afatinib Based on the Percentage of Participants Experienced Dose Limiting Toxicities   [ Time Frame: first treatment cycle, up to 28 days ]

2.  Secondary:   Overall Tumour Response Rate Assessed by the Investigator According to the Response Evaluation Criteria In Solid Tumours (RECIST) Version 1.1   [ Time Frame: 6 weeks ]

3.  Secondary:   Incidence and Intensity of Adverse Events According to CTCAE (Common Toxicity Criteria Adverse Event) Version 3.0   [ Time Frame: First treatment administration until cut-off date of 02Oct2014; up to 336 days ]

4.  Secondary:   Changes in Safety Laboratory Parameters   [ Time Frame: First treatment administration until cut-off date of 02 October 2014, up to 336 days ]

5.  Secondary:   Cpre,ss,Norm (Dose Normalized Trough Plasma Concentration of Nintedanib at Steady State)   [ Time Frame: Day 8, Day 15, Day 22 and Day 28 ]

6.  Secondary:   Trough Plasma Concentration of Afatinib at Steady State   [ Time Frame: Day 7, Day 13, Day 15, Day 22, Day 27 and Day 28 ]

7.  Secondary:   Objective Response (OR) During the Expansion Phase   [ Time Frame: Tumour assessment was to be performed at Screening, every 6 weeks after starting study treatment until disease progression, and at the end-of-treatment (EOT) visit (up to 1117 days) ]

8.  Secondary:   Disease Control (DC) During the Expansion Phase   [ Time Frame: Tumour assessment was to be performed at Screening, every 6 weeks after starting study treatment until disease progression, and at the end-of-treatment (EOT) visit (up to 1117 days) ]

9.  Secondary:   Stable Disease for at Least 12 Weeks During the Expansion Phase   [ Time Frame: Tumour assessment was to be performed at Screening, every 6 weeks after starting study treatment until disease progression, and at the end-of-treatment (EOT) visit (up to 1117 days) ]

10.  Secondary:   Percentage Change in the Tumour Size From Baseline During the Expansion Phase   [ Time Frame: Tumour assessment was to be performed at Screening, every 6 weeks after starting study treatment until disease progression, and at the end-of-treatment (EOT) visit (up to 1117 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
Statistics of PK parameters are only estimated when at least 2/3 of the data are evaluable.


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


No publications provided


Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00998296     History of Changes
Other Study ID Numbers: 1239.14, 2009-011321-14
Study First Received: October 19, 2009
Results First Received: November 14, 2014
Last Updated: July 23, 2015
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
United States: Food and Drug Administration