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)
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ClinicalTrials.gov Identifier: NCT01449461 |
Recruitment Status :
Completed
First Posted : October 10, 2011
Results First Posted : June 21, 2017
Last Update Posted : August 17, 2021
|
Sponsor:
Ariad Pharmaceuticals
Information provided by (Responsible Party):
Takeda ( Ariad Pharmaceuticals )
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Study Type | Interventional |
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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 |
Enrollment | 137 |
Participant Flow
Recruitment Details | Participants took part in the study at 9 investigative sites in the United States and Spain from 20 September 2011 to 18 February 2020. |
Pre-assignment Details | 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. |
Arm/Group Title | 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 |
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Arm/Group Description | Brigatinib 30 mg/60 mg, tablets, orally, once daily (QD) in each cycle of 28 days (Approximately up to 7.3 years). | Brigatinib 90 mg, tablets, orally, QD in each cycle of 28 days (Approximately up to 7.3 years). | Brigatinib 120 mg, once daily or 60 mg, twice daily (BID), tablets, orally, in each cycle of 28 days (Approximately up to 7.3 years). | Brigatinib 90 mg, tablets, orally, once daily for 7 days followed by brigatinib 180 mg, orally QD in Cycle 1 of 28 days followed by brigatinib 180 mg, orally QD in cycle 2 and onward cycles of 28 days (Approximately up to 7.3 years). | Brigatinib 180 mg, once daily or 90 mg, BID, tablets, orally in each cycle of 28 days (Approximately up to 7.3 years). | Brigatinib 240 mg, QD or 120 mg, BID or 300 mg once daily, tablets, orally, in each cycle of 28 days (Approximately up to 7.3 years). |
Period Title: Overall Study | ||||||
Started | 6 | 18 | 18 | 32 | 48 | 15 |
Completed | 0 | 0 | 0 | 0 | 0 | 0 |
Not Completed | 6 | 18 | 18 | 32 | 48 | 15 |
Reason Not Completed | ||||||
Adverse Event | 0 | 3 | 2 | 3 | 4 | 4 |
Death | 0 | 2 | 0 | 0 | 7 | 1 |
Physician Decision | 0 | 1 | 0 | 4 | 1 | 0 |
Documented Progressive Disease | 4 | 7 | 14 | 15 | 24 | 5 |
Clinical Progressive Disease | 2 | 2 | 0 | 3 | 4 | 2 |
Protocol Violation | 0 | 0 | 0 | 1 | 0 | 0 |
Site Terminated by Sponsor | 0 | 1 | 2 | 3 | 4 | 1 |
Withdrawal by Subject | 0 | 1 | 0 | 0 | 2 | 1 |
Reason not Specified | 0 | 1 | 0 | 3 | 2 | 1 |
Baseline Characteristics
Arm/Group Title | 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 | |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | Brigatinib 30 mg/60 mg, tablets, orally, QD in each cycle of 28 days (Approximately up to 7.3 years). | Brigatinib 90 mg, tablets, orally, QD in each cycle of 28 days (Approximately up to 7.3 years). | Brigatinib 120 mg, once daily or 60 mg, BID, tablets, orally, in each cycle of 28 days (Approximately up to 7.3 years). | Brigatinib 90 mg, tablets, orally, once daily for 7 days followed by brigatinib 180 mg, orally QD in Cycle 1 of 28 days followed by brigatinib 180 mg, orally QD in cycle 2 and onward cycles of 28 days (Approximately up to 7.3 years). | Brigatinib 180 mg, once daily or 90 mg, BID, tablets, orally in each cycle of 28 days (Approximately up to 7.3 years). | Brigatinib 240 mg, QD or 120 mg, BID or 300 mg once daily, tablets, orally, in each cycle of 28 days (Approximately up to 7.3 years). | Total of all reporting groups | |
Overall Number of Baseline Participants | 6 | 18 | 18 | 32 | 48 | 15 | 137 | |
Baseline Analysis Population Description |
Safety population included all enrolled participants who received at least one dose of study drug.
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Age, Continuous
Mean (Standard Deviation) Unit of measure: Years |
||||||||
Number Analyzed | 6 participants | 18 participants | 18 participants | 32 participants | 48 participants | 15 participants | 137 participants | |
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
Measure Type: Count of Participants Unit of measure: Participants |
||||||||
Number Analyzed | 6 participants | 18 participants | 18 participants | 32 participants | 48 participants | 15 participants | 137 participants | |
Adults [18-64 years] |
2 33.3%
|
11 61.1%
|
12 66.7%
|
25 78.1%
|
39 81.3%
|
9 60.0%
|
98 71.5%
|
|
From 65 to 84 years |
4 66.7%
|
7 38.9%
|
6 33.3%
|
7 21.9%
|
9 18.8%
|
6 40.0%
|
39 28.5%
|
|
Sex: Female, Male
Measure Type: Count of Participants Unit of measure: Participants |
||||||||
Number Analyzed | 6 participants | 18 participants | 18 participants | 32 participants | 48 participants | 15 participants | 137 participants | |
Female |
3 50.0%
|
12 66.7%
|
13 72.2%
|
14 43.8%
|
29 60.4%
|
8 53.3%
|
79 57.7%
|
|
Male |
3 50.0%
|
6 33.3%
|
5 27.8%
|
18 56.3%
|
19 39.6%
|
7 46.7%
|
58 42.3%
|
|
Race/Ethnicity, Customized
Measure Type: Count of Participants Unit of measure: Participants |
||||||||
Number Analyzed | 6 participants | 18 participants | 18 participants | 32 participants | 48 participants | 15 participants | 137 participants | |
American Indian or Alaska Native |
0 0.0%
|
0 0.0%
|
0 0.0%
|
1 3.1%
|
1 2.1%
|
0 0.0%
|
2 1.5%
|
|
Asian |
0 0.0%
|
4 22.2%
|
3 16.7%
|
3 9.4%
|
5 10.4%
|
2 13.3%
|
17 12.4%
|
|
Black or African American |
0 0.0%
|
1 5.6%
|
2 11.1%
|
0 0.0%
|
1 2.1%
|
1 6.7%
|
5 3.6%
|
|
Native Hawaiian or Other Pacific Islander |
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
1 2.1%
|
0 0.0%
|
1 0.7%
|
|
White |
6 100.0%
|
13 72.2%
|
13 72.2%
|
27 84.4%
|
39 81.3%
|
12 80.0%
|
110 80.3%
|
|
Unknown |
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
1 2.1%
|
0 0.0%
|
1 0.7%
|
|
Other |
0 0.0%
|
0 0.0%
|
0 0.0%
|
1 3.1%
|
0 0.0%
|
0 0.0%
|
1 0.7%
|
|
Race/Ethnicity, Customized
Measure Type: Count of Participants Unit of measure: Participants |
||||||||
Number Analyzed | 6 participants | 18 participants | 18 participants | 32 participants | 48 participants | 15 participants | 137 participants | |
Hispanic or Latino |
1 16.7%
|
0 0.0%
|
0 0.0%
|
1 3.1%
|
1 2.1%
|
0 0.0%
|
3 2.2%
|
|
Not Hispanic or Latino |
5 83.3%
|
18 100.0%
|
18 100.0%
|
31 96.9%
|
47 97.9%
|
15 100.0%
|
134 97.8%
|
|
Region of Enrollment
Measure Type: Count of Participants Unit of measure: Participants |
Number Analyzed | 6 participants | 18 participants | 18 participants | 32 participants | 48 participants | 15 participants | 137 participants |
United States |
6 100.0%
|
18 100.0%
|
18 100.0%
|
32 100.0%
|
41 85.4%
|
15 100.0%
|
130 94.9%
|
|
Spain |
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
7 14.6%
|
0 0.0%
|
7 5.1%
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Score
[1] Measure Type: Count of Participants Unit of measure: Participants |
||||||||
Number Analyzed | 6 participants | 18 participants | 18 participants | 32 participants | 48 participants | 15 participants | 137 participants | |
0 |
0 0.0%
|
3 16.7%
|
3 16.7%
|
13 40.6%
|
13 27.1%
|
2 13.3%
|
34 24.8%
|
|
1 |
6 100.0%
|
15 83.3%
|
15 83.3%
|
19 59.4%
|
33 68.8%
|
13 86.7%
|
101 73.7%
|
|
2 |
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
2 4.2%
|
0 0.0%
|
2 1.5%
|
|
[1]
Measure Description: 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.
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Time Since Diagnosis of Cancer
Mean (Standard Deviation) Unit of measure: Years |
||||||||
Number Analyzed | 6 participants | 18 participants | 18 participants | 32 participants | 48 participants | 15 participants | 137 participants | |
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
Measure Type: Count of Participants Unit of measure: Participants |
||||||||
Number Analyzed | 6 participants | 18 participants | 18 participants | 32 participants | 48 participants | 15 participants | 137 participants | |
NSCLC |
3 50.0%
|
16 88.9%
|
18 100.0%
|
31 96.9%
|
45 93.8%
|
15 100.0%
|
128 93.4%
|
|
Other |
3 50.0%
|
2 11.1%
|
0 0.0%
|
1 3.1%
|
3 6.3%
|
0 0.0%
|
9 6.6%
|
|
Number of Participants with Mutation Types
Measure Type: Count of Participants Unit of measure: Participants |
||||||||
Number Analyzed | 6 participants | 18 participants | 18 participants | 32 participants | 48 participants | 15 participants | 137 participants | |
Anaplastic Lymphoma Kinase (ALK+) |
1 16.7%
|
16 88.9%
|
6 33.3%
|
29 90.6%
|
27 56.3%
|
5 33.3%
|
84 61.3%
|
|
Epidermal Growth Factor Receptor (EGFRm) |
2 33.3%
|
1 5.6%
|
10 55.6%
|
3 9.4%
|
18 37.5%
|
9 60.0%
|
43 31.4%
|
|
ROS Proto-oncogene 1 (ROS1+) |
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
3 6.3%
|
1 6.7%
|
4 2.9%
|
|
Other |
3 50.0%
|
1 5.6%
|
2 11.1%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
6 4.4%
|
|
Participants with Prior Chemotherapy Regimen
Measure Type: Count of Participants Unit of measure: Participants |
||||||||
Number Analyzed | 6 participants | 18 participants | 18 participants | 32 participants | 48 participants | 15 participants | 137 participants | |
0 |
0 0.0%
|
2 11.1%
|
7 38.9%
|
12 37.5%
|
12 25.0%
|
3 20.0%
|
36 26.3%
|
|
1 |
3 50.0%
|
4 22.2%
|
3 16.7%
|
6 18.8%
|
17 35.4%
|
2 13.3%
|
35 25.5%
|
|
2 |
0 0.0%
|
9 50.0%
|
4 22.2%
|
8 25.0%
|
10 20.8%
|
5 33.3%
|
36 26.3%
|
|
> 2 |
3 50.0%
|
3 16.7%
|
4 22.2%
|
6 18.8%
|
9 18.8%
|
5 33.3%
|
30 21.9%
|
|
Participants with Prior Radiotherapy to Brain
Measure Type: Count of Participants Unit of measure: Participants |
||||||||
Number Analyzed | 6 participants | 18 participants | 18 participants | 32 participants | 48 participants | 15 participants | 137 participants | |
No |
6 100.0%
|
13 72.2%
|
17 94.4%
|
24 75.0%
|
36 75.0%
|
14 93.3%
|
110 80.3%
|
|
Yes |
0 0.0%
|
5 27.8%
|
1 5.6%
|
8 25.0%
|
12 25.0%
|
1 6.7%
|
27 19.7%
|
Outcome Measures
Adverse Events
Limitations and Caveats
[Not Specified]
More Information
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 first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Results Point of Contact
Name/Title: | Medical Director |
Organization: | Takeda |
Phone: | +1-877-825-3327 |
EMail: | trialdisclosures@takeda.com |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Takeda ( Ariad Pharmaceuticals ) |
ClinicalTrials.gov Identifier: | NCT01449461 |
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: | August 17, 2021 |