A Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of GSK525762 in Subjects With NUT Midline Carcinoma (NMC) and Other Cancers
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ClinicalTrials.gov Identifier: NCT01587703 |
Recruitment Status :
Completed
First Posted : April 30, 2012
Results First Posted : March 16, 2020
Last Update Posted : March 16, 2020
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Sponsor:
GlaxoSmithKline
Information provided by (Responsible Party):
GlaxoSmithKline
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Study Type | Interventional |
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Study Design | Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment |
Condition |
Carcinoma, Midline |
Intervention |
Drug: GSK525762 |
Enrollment | 196 |
Participant Flow
Recruitment Details | A total 196 participants were enrolled and randomized in the Part 1 QD (65 participants), Part 1 BID (19 participants), Besylate Substudy (10 participants), and Part 2 (102 participants) groups. |
Pre-assignment Details | This was a 2-Part study conducted in 8 countries-Part 1 (dose-escalation) and Part 2 (dose expansion). A besylate sub-study (four period, crossover) was conducted in 10 participants in the United States. |
Arm/Group Title | Part 1: GSK525762 2 mg QD | Part 1: GSK525762 4 mg QD | Part 1: GSK525762 8 mg QD | Part 1: GSK525762 16 mg QD | Part 1: GSK525762 30 mg QD | Part 1: GSK525762 60 mg QD | Part 1: GSK525762 80 mg QD | Part 1: GSK525762 100 mg QD | Part 1: GSK525762 20 mg BID | Part 1: GSK525762 30 mg BID | Part 1: GSK525762 40 mg BID | Part 2: Participants With NMC | Part 2: Participants With SCLC | Part 2: Participants With CRPC | Part 2: Participants With TNBC | Part 2: Participants With ER+BC | Part 2: Participants With GIST | 80mg Amor+6mg Iso/80mg Bes+6mg Iso/30mg Bes+6mg Iso/80mg Bes | 80mg Bes+6mg Iso/80mg Amor+6mg Iso/30mg Bes+6mg Iso/80mg Bes |
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Participants were administered once daily (QD) oral dose of 2 milligrams (mg) GSK525762. | Participants were administered once daily oral dose of 4 mg GSK525762 | Participants were administered once daily oral dose of 8 mg GSK525762. | Participants were administered once daily oral dose of 16 mg GSK525762. | Participants were administered once daily oral dose of 30 mg GSK525762. | Participants were administered once daily oral dose of 60 mg GSK525762. | Participants were administered once daily oral dose of 80 mg GSK525762. | Participants were administered once daily oral dose of 100 mg GSK525762. | Participants were administered twice daily (BID) oral dose of 20 mg GSK525762. | Participants were administered twice daily oral dose of 30 mg GSK525762. | Participants were administered twice daily oral dose of 40 mg GSK525762. | Participants with NUT Midline Carcinoma (NMC) were administered continuous once daily oral dose of 75 mg GSK525762. | Participants with small cell lung cancer(SCLC) were administered continuous once daily oral dose of 75 mg GSK525762 | Participants with Castrate-Resistant Prostate Cancer (CRPR) were administered continuous once daily oral dose of 75 mg GSK525762 | Participants with Triple Negative Breast Cancer (TNBC) were administered continuous once daily oral dose of 75 mg GSK525762. | Participants with estrogen receptor positive breast cancer (ER+BC) were administered continuous once daily oral dose of 75 mg GSK525762 | Participants with Gastrointestinal Stromal Tumor (GIST) were administered continuous once daily oral dose of 75 mg GSK525762. | Participants received GSK525762 80 mg amorphous (amor) free-base tablet along with 6 mg stable isotope (iso) in solution in the fasted state in Period 1 followed by administration of GSK525762 80 mg besylate (bes) tablet along with 6 mg stable iso in solution in the fasted state in Period 2. Participants were then administered GSK525762 30 mg bes tablet along with 6 mg stable iso in solution in the fasted state in Period 3 and GSK525762 80 mg bes tablet was administered with Food and Drug Administration (FDA) recommended high fat breakfast in Period 4. | Participants received GSK525762 80 mg bes tablet along with 6 mg stable iso in solution in the fasted state in Period 1 followed by administration GSK525762 80 mg amor free-base tablet along with 6 mg stable iso in solution in the fasted state in Period 2. Participants were then administered GSK525762 30 mg bes tablet along with 6 mg stable iso in solution in the fasted state in Period 3 and GSK525762 80 mg bes tablet was administered with FDA recommended high fat breakfast in Period 4. |
Period Title: Part1 QD(Median Exposure of 1.38months) | |||||||||||||||||||
Started | 3 | 4 | 1 | 3 | 4 | 9 | 32 | 9 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Completed | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Not Completed | 3 | 4 | 1 | 3 | 4 | 8 | 32 | 9 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Reason Not Completed | |||||||||||||||||||
Physician Decision | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Site closed | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Death | 2 | 4 | 1 | 3 | 4 | 7 | 30 | 7 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Part1 BID(Median Exposure of 1.41months) | |||||||||||||||||||
Started | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 10 | 5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Not Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 10 | 5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Reason Not Completed | |||||||||||||||||||
Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 9 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Site closed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Substudy-Period(P)1, Week1(Day1 to Day3) | |||||||||||||||||||
Started | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 5 |
Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 5 |
Not Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Substudy-P2, Week1Day3 to Week2Day1 | |||||||||||||||||||
Started | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 5 |
Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 5 |
Not Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Substudy-P3, Week2Day1 to Week2Day3 | |||||||||||||||||||
Started | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 5 |
Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 5 |
Not Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Substudy-P4,Maximum Exposure of 5.5month | |||||||||||||||||||
Started | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 5 |
Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Not Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 5 |
Reason Not Completed | |||||||||||||||||||
Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 4 |
Period Title: Part2(Median Exposure of 1.41 Months) | |||||||||||||||||||
Started | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 12 | 14 | 23 | 19 | 21 | 13 | 0 | 0 |
Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
Not Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 12 | 14 | 22 | 19 | 21 | 13 | 0 | 0 |
Reason Not Completed | |||||||||||||||||||
Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 2 | 0 | 0 | 0 | 0 |
Site closed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 1 | 1 | 3 | 8 | 0 | 0 |
Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 8 | 12 | 21 | 16 | 17 | 5 | 0 | 0 |
Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline Characteristics
Arm/Group Title | Part 1: GSK525762 4 mg QD | Part 1: GSK525762 8 mg QD | Part 1: GSK525762 16 mg QD | Part 1: GSK525762 30 mg QD | Part 1: GSK525762 60 mg QD | Part 1: GSK525762 80 mg QD | Part 1: GSK525762 100 mg QD | Part 1: GSK525762 20 mg BID | Part 1: GSK525762 30 mg BID | Part 1: GSK525762 40 mg BID | All Participants in Besylate Substudy | Part 2: Participants With NMC | Part 2: Participants With SCLC | Part 2: Participants With CRPC | Part 1: GSK525762 2 mg QD | Part 2: Participants With TNBC | Part 2: Participants With ER+BC | Part 2: Participants With GIST | Total | |
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Participants were administered once daily oral dose of 4 mg GSK525762 | Participants were administered once daily oral dose of 8 mg GSK525762. | Participants were administered once daily oral dose of 16 mg GSK525762. | Participants were administered once daily oral dose of 30 mg GSK525762. | Participants were administered once daily oral dose of 60 mg GSK525762. | Participants were administered once daily oral dose of 80 mg GSK525762. | Participants were administered once daily oral dose of 100 mg GSK525762. | Participants were administered twice daily (BID) oral dose of 20 mg GSK525762. | Participants were administered twice daily oral dose of 30 mg GSK525762. | Participants were administered twice daily oral dose of 40 mg GSK525762. | All participants who entered besylate sub-study and received 80 mg amor free-base tablet along with 6 mg stable iso in solution in fasted state; 80 mg bes tablet along with 6 mg stable iso in solution in fasted state, 30 mg bes tablet along with 6 mg stable iso in solution in fasted state and 80 mg bes tablet with FDA recommended high fat breakfast in one of the treatment periods were included. | Participants with NUT Midline Carcinoma (NMC) were administered continuous once daily oral dose of 75 mg GSK525762. | Participants with small cell lung cancer(SCLC) were administered continuous once daily oral dose of 75 mg GSK525762 | Participants with Castrate-Resistant Prostate Cancer (CRPR) were administered continuous once daily oral dose of 75 mg GSK525762 | Participants were administered once daily (QD) oral dose of 2 milligrams (mg) GSK525762. | Participants with Triple Negative Breast Cancer (TNBC) were administered continuous once daily oral dose of 75 mg GSK525762. | Participants with estrogen receptor positive breast cancer (ER+BC) were administered continuous once daily oral dose of 75 mg GSK525762 | Participants with Gastrointestinal Stromal Tumor (GIST) were administered continuous once daily oral dose of 75 mg GSK525762. | Total of all reporting groups | |
Overall Number of Baseline Participants | 4 | 1 | 3 | 4 | 9 | 32 | 9 | 4 | 10 | 5 | 10 | 12 | 14 | 23 | 3 | 19 | 21 | 13 | 196 | |
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[Not Specified]
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Age, Continuous
Mean (Standard Deviation) Unit of measure: Years |
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Number Analyzed | 4 participants | 1 participants | 3 participants | 4 participants | 9 participants | 32 participants | 9 participants | 4 participants | 10 participants | 5 participants | 10 participants | 12 participants | 14 participants | 23 participants | 3 participants | 19 participants | 21 participants | 13 participants | 196 participants | |
47.0 (19.44) | 39.0 [1] (NA) | 53.7 (4.19) | 49.3 (23.27) | 46.7 (17.06) | 51.5 (16.82) | 58.3 (19.92) | 66.5 (6.45) | 63.5 (8.42) | 60.4 (4.83) | 55.2 (9.96) | 42.9 (18.05) | 58.3 (11.04) | 63.8 (6.11) | 40.0 (15.77) | 50.8 (8.66) | 59.7 (10.34) | 61.0 (13.23) | 55.4 (14.37) | ||
[1]
Standard deviation could not be calculated as only one participant was analyzed
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Sex: Female, Male
Measure Type: Count of Participants Unit of measure: Participants |
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Number Analyzed | 4 participants | 1 participants | 3 participants | 4 participants | 9 participants | 32 participants | 9 participants | 4 participants | 10 participants | 5 participants | 10 participants | 12 participants | 14 participants | 23 participants | 3 participants | 19 participants | 21 participants | 13 participants | 196 participants | |
Female |
3 75.0%
|
1 100.0%
|
3 100.0%
|
1 25.0%
|
6 66.7%
|
14 43.8%
|
2 22.2%
|
2 50.0%
|
4 40.0%
|
1 20.0%
|
5 50.0%
|
7 58.3%
|
9 64.3%
|
0 0.0%
|
1 33.3%
|
19 100.0%
|
21 100.0%
|
6 46.2%
|
105 53.6%
|
|
Male |
1 25.0%
|
0 0.0%
|
0 0.0%
|
3 75.0%
|
3 33.3%
|
18 56.3%
|
7 77.8%
|
2 50.0%
|
6 60.0%
|
4 80.0%
|
5 50.0%
|
5 41.7%
|
5 35.7%
|
23 100.0%
|
2 66.7%
|
0 0.0%
|
0 0.0%
|
7 53.8%
|
91 46.4%
|
|
Race/Ethnicity, Customized
Measure Type: Count of Participants Unit of measure: Participants |
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Number Analyzed | 4 participants | 1 participants | 3 participants | 4 participants | 9 participants | 32 participants | 9 participants | 4 participants | 10 participants | 5 participants | 10 participants | 12 participants | 14 participants | 23 participants | 3 participants | 19 participants | 21 participants | 13 participants | 196 participants | |
American Indian or Alaska Native |
0 0.0%
|
1 100.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
1 0.5%
|
|
Central/South Asian Heritage (Her) |
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
1 11.1%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
1 8.3%
|
0 0.0%
|
0 0.0%
|
1 33.3%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
3 1.5%
|
|
Japanese Her/East Asian Her/South East Asian Her |
1 25.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
1 25.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
2 16.7%
|
3 21.4%
|
0 0.0%
|
0 0.0%
|
1 5.3%
|
0 0.0%
|
1 7.7%
|
9 4.6%
|
|
Black or African American |
0 0.0%
|
0 0.0%
|
1 33.3%
|
0 0.0%
|
1 11.1%
|
2 6.3%
|
1 11.1%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
1 10.0%
|
0 0.0%
|
2 14.3%
|
0 0.0%
|
0 0.0%
|
2 10.5%
|
1 4.8%
|
1 7.7%
|
12 6.1%
|
|
White |
3 75.0%
|
0 0.0%
|
2 66.7%
|
4 100.0%
|
7 77.8%
|
30 93.8%
|
8 88.9%
|
3 75.0%
|
10 100.0%
|
5 100.0%
|
9 90.0%
|
6 50.0%
|
8 57.1%
|
23 100.0%
|
2 66.7%
|
15 78.9%
|
18 85.7%
|
10 76.9%
|
163 83.2%
|
|
Missing |
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
3 25.0%
|
1 7.1%
|
0 0.0%
|
0 0.0%
|
1 5.3%
|
2 9.5%
|
1 7.7%
|
8 4.1%
|