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A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-Tumor Activity of the Oral Anaplastic Lymphoma Kinase (ALK)/Epidermal Growth Factor Receptor (EGFR) Inhibitor Brigatinib (AP26113)

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01449461
First Posted: October 10, 2011
Last Update Posted: October 3, 2017
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.
Information provided by (Responsible Party):
Ariad Pharmaceuticals
Results First Submitted: May 26, 2017  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions: Lymphoma, Large-Cell, Anaplastic
Carcinoma, Non-Small-Cell Lung
Intervention: Drug: Brigatinib

  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
Participants took part in the study at 9 investigative sites in the United States and Spain up to clinical cut-off date 16 November 2015. Study is ongoing.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants with advanced malignancies, all histologies other than leukemia were enrolled in dose-escalation and participants with non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangements were enrolled in dose expansion phase. Participants received brigatinib 30 mg - 300 mg, tablets, orally once daily or twice daily.

Reporting Groups
  Description
Brigatinib 30 mg QD/60 mg QD Brigatinib 30 mg/60 mg, tablets, orally, once daily (QD) in each cycle of 28 days (approximately, up to 44.4 months).
Brigatinib 90 mg QD Brigatinib 90 mg, tablets, orally, once daily (QD) in each cycle of 28 days (approximately, up to 44.4 months).
Brigatinib 120 mg QD/60 mg BID Brigatinib 120 mg, once daily or 60 mg, twice daily (BID), tablets, orally, in each cycle of 28 days (approximately, up to 44.4 months).
Brigatinib 90 mg QD-180 mg QD Brigatinib 90 mg, tablets, orally, once daily for 7 days followed by brigatinib 180 mg, orally once daily in Cycle 1 of 28 days followed by brigatinib 180 mg, orally once daily in cycle 2 and onward cycles of 28 days.
Brigatinib 180 mg QD/90 mg BID Brigatinib 180 mg, once daily or 90 mg, twice daily (BID), tablets, orally in each cycle of 28 days (approximately, up to 44.4 months).
Brigatinib 240 mg QD/120 mg BID/300 mg QD Brigatinib 240 mg, once daily (QD) or 120 mg, twice daily (BID) or 300 mg once daily, tablets, orally, in each cycle of 28 days (approximately, up to 44.4 months).

Participant Flow:   Overall Study
    Brigatinib 30 mg QD/60 mg QD   Brigatinib 90 mg QD   Brigatinib 120 mg QD/60 mg BID   Brigatinib 90 mg QD-180 mg QD   Brigatinib 180 mg QD/90 mg BID   Brigatinib 240 mg QD/120 mg BID/300 mg QD
STARTED   6   18   18   32   48   15 
COMPLETED   0   0   0   0   0   0 
NOT COMPLETED   6   18   18   32   48   15 
Ongoing                0                6                2                15                17                2 
Adverse Event                0                3                2                3                3                3 
Death                0                1                0                0                4                1 
Documented progressive disease                4                6                14                11                21                5 
Clinical progressive disease                2                1                0                0                3                3 
Reason not specified                0                1                0                3                0                1 



  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.
Safety population included all enrolled participants who received at least one dose of study drug.

Reporting Groups
  Description
Brigatinib 30 mg QD/60 mg QD Brigatinib 30 mg/60 mg, tablets, orally, once daily (QD) in each cycle of 28 days (approximately, up to 44.4 months).
Brigatinib 90 mg QD Brigatinib 90 mg, tablets, orally, once daily (QD) in each cycle of 28 days (approximately, up to 44.4 months).
Brigatinib 120 mg QD/60 mg BID Brigatinib 120 mg, once daily or 60 mg, twice daily (BID), tablets, orally, in each cycle of 28 days (approximately, up to 44.4 months).
Brigatinib 90 mg QD-180 mg QD Brigatinib 90 mg, tablets, orally, once daily for 7 days followed by brigatinib 180 mg, orally once daily in Cycle 1 of 28 days followed by brigatinib 180 mg, orally once daily in cycle 2 and onward cycles of 28 days.
Brigatinib 180 mg QD/90 mg BID Brigatinib 180 mg, once daily or 90 mg, twice daily (BID), tablets, orally in each cycle of 28 days (approximately, up to 44.4 months).
Brigatinib 240 mg QD/120 mg BID/300 mg QD Brigatinib 240 mg, once daily (QD) or 120 mg, twice daily (BID) or 300 mg once daily, tablets, orally, in each cycle of 28 days (approximately, up to 44.4 months).
Total Total of all reporting groups

Baseline Measures
   Brigatinib 30 mg QD/60 mg QD   Brigatinib 90 mg QD   Brigatinib 120 mg QD/60 mg BID   Brigatinib 90 mg QD-180 mg QD   Brigatinib 180 mg QD/90 mg BID   Brigatinib 240 mg QD/120 mg BID/300 mg QD   Total 
Overall Participants Analyzed 
[Units: Participants]
 6   18   18   32   48   15   137 
Age 
[Units: Years]
Mean (Standard Deviation)
 66.8  (9.30)   57.9  (12.93)   57.8  (10.91)   55.7  (11.41)   53.9  (11.10)   58.5  (15.60)   56.4  (12.02) 
Age, Customized 
[Units: Participants]
             
18 – 64 years   2   11   12   25   39   9   98 
≥65 years   4   7   6   7   9   6   39 
Sex: Female, Male 
[Units: Participants]
Count of Participants
             
Female      3  50.0%      6  33.3%      5  27.8%      18  56.3%      19  39.6%      7  46.7%      58  42.3% 
Male      3  50.0%      12  66.7%      13  72.2%      14  43.8%      29  60.4%      8  53.3%      79  57.7% 
Race/Ethnicity, Customized 
[Units: Participants]
             
American Indian or Alaska Native   0   0   0   1   1   0   2 
Asian   0   4   3   3   5   2   17 
Black or African American   0   1   2   0   1   1   5 
Native Hawaiian or Other Pacific Islander   0   0   0   0   1   0   1 
White   6   13   13   27   39   12   110 
Unknown   0   0   0   0   1   0   1 
Other   0   0   0   1   0   0   1 
Race/Ethnicity, Customized 
[Units: Participants]
             
Hispanic or Latino   1   0   0   1   1   0   3 
Not Hispanic or Latino   5   18   18   31   47   15   134 
Region of Enrollment 
[Units: Participants]
             
United States   6   18   18   32   41   15   130 
Spain   0   0   0   0   7   0   7 
Eastern Cooperative Oncology Group (ECOG) Performance Score [1] 
[Units: Participants]
             
 0   3   3   13   13   2   34 
 6   15   15   19   33   13   101 
 0   0   0   0   2   0   2 
[1] ECOG assessed participant's performance status on a 5 point scale: 0 equals (=) fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, but ambulatory/able to carry out light or sedentary work; 2=ambulatory (greater than [>] 50 percentage [%] of waking hours [h]), capable of all self care, but unable to carry out any work activities; 3=capable of only limited self care, confined to bed/chair >50% of waking hours; 4= completely disabled, cannot carry on any selfcare, totally confined to bed or chair and 5=Dead.
Time Since Diagnosis of Cancer 
[Units: Years]
Mean (Standard Deviation)
 2.48  (3.303)   3.33  (2.184)   2.41  (1.346)   3.19  (2.726)   2.77  (2.053)   3.27  (1.913)   2.93  (2.192) 
Participants with Diagnosis of Cancer Type 
[Units: Participants]
             
NSCLC   3   16   18   31   45   15   128 
Other   3   2   0   1   3   0   9 
Number of Participants with Mutation Types 
[Units: Participants]
             
anaplastic lymphoma kinase (ALK+)   1   16   6   29   27   5   84 
Epidermal Growth Factor Receptor (EGFRm)   2   1   10   3   18   9   43 
ROS proto-oncogene 1 (ROS1+)   0   0   0   0   3   1   4 
Other   3   1   2   0   0   0   6 
Participants with Prior Chemotherapy Regimen 
[Units: Participants]
             
 0   2   7   12   12   3   36 
 3   4   3   6   17   2   35 
 0   9   4   8   10   5   36 
> 2   3   3   4   6   9   5   30 
Participants with Prior Radiotherapy to Brain 
[Units: Participants]
             
No   6   13   17   24   36   14   110 
Yes   0   5   1   8   12   1   27 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Recommended Phase 2 Dose of Brigatinib   [ Time Frame: 28 days ]

2.  Primary:   Objective Response Rate (ORR)   [ Time Frame: Screening and at 8-week intervals thereafter up to data cut-off date: 16 November 2015 (approximately up to 50 months) ]

3.  Secondary:   Number of Participants Who Had at Least One Treatment-Emergent Adverse Event (TEAE)   [ Time Frame: Any adverse event reported on or after the day of first dose of study drug (approximately up to 50 months) ]

4.  Secondary:   Maximum Tolerated Dose (MTD) Assessed in Dose Escalation Phase of the Study   [ Time Frame: Up to Cycle 1 (28 days) ]

5.  Secondary:   Number of Participants With Dose Limiting Toxicities (DLTs) Assessed in Dose Escalation Phase of the Study   [ Time Frame: Up to Cycle 1 (28 days) ]

6.  Secondary:   Cmax: Maximum Observed Plasma Concentration for Brigatinib   [ Time Frame: Cycle 1 Day 1 ]

7.  Secondary:   Cmax: Maximum Observed Plasma Concentration for Brigatinib   [ Time Frame: Cycle 2 Day 2 ]

8.  Secondary:   Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Brigatinib   [ Time Frame: Cycle 1 Day 1 ]

9.  Secondary:   Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Brigatinib   [ Time Frame: Cycle 2 Day 1 ]

10.  Secondary:   AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Post-dose for Brigatinib   [ Time Frame: Cycle 1 Day 1, 8, 15 and 22 pre-dose and Day 1 multiple timepoints (up to 48 hours) post-dose; Cycle 2 Day 1 and 3 pre-dose and Day 1 multiple time points (up to 48 hours) post-dose ]

11.  Secondary:   Terminal Phase Elimination Half-life (T1/2) for Brigatinib   [ Time Frame: Cycle 2 Day 1 ]

12.  Secondary:   Best Overall Response   [ Time Frame: Screening and at 8-week intervals thereafter up to data cut-off date: 16 November 2015 (approximately up to 50 months) ]

13.  Secondary:   Duration of Response   [ Time Frame: Screening and at 8-week intervals thereafter up to data cut-off date: 16 November 2015 (approximately up to 50 months) ]

14.  Secondary:   Progression Free Survival (PFS)   [ Time Frame: Screening and at 8-week intervals thereafter up to data cut-off date: 16 November 2015 (approximately up to 50 months) ]

15.  Secondary:   Overall Survival (OS)   [ Time Frame: Screening and at 8-week intervals thereafter up to data cut-off date: 16 November 2015 (approximately up to 50 months) ]

16.  Secondary:   Intracranial Objective Response Rate   [ Time Frame: Screening and at 8-week intervals thereafter up to data cut-off date: 16 November 2015 (approximately up to 50 months) ]

17.  Secondary:   Duration of Intracranial Response   [ Time Frame: Screening and at 8-week intervals thereafter up to data cut-off date: 16 November 2015 (approximately up to 50 months) ]

18.  Secondary:   Intracranial Progression Free Survival (PFS)   [ Time Frame: Screening and at 8-week intervals thereafter up to data cut-off date: 16 November 2015 (approximately up to 50 months) ]


  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
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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: Medical Director
Organization: Takeda
phone: +1-877-825-3327
e-mail: trialdisclosures@takeda.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Ariad Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01449461     History of Changes
Other Study ID Numbers: AP26113-11-101
2011-005718-12 ( EudraCT Number )
U1111-1196-8197 ( Other Identifier: World Health Organization )
First Submitted: September 30, 2011
First Posted: October 10, 2011
Results First Submitted: May 26, 2017
Results First Posted: June 21, 2017
Last Update Posted: October 3, 2017