Trial Outcomes & Findings for Dose-finding Study in Platinum-Resistant Ovarian Cancer (NCT NCT01653912)
NCT ID: NCT01653912
Last Updated: 2018-04-02
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
59 participants
Primary outcome timeframe
Up to Week 3
Results posted on
2018-04-02
Participant Flow
Subjects were enrolled at 10 centers in 3 countries (United Kingdom, Australia, and Russia)
As described in Statistical Analysis Plan (SAP) dated 14-Jul-2015, as there were \<10 subjects in Cohort B (n=2), data was summarized in phase 2 total column but not presented in a separate column for Cohort B.
Participant milestones
| Measure |
Phase 1 (Dose Escalation)-Cohort 1: GSK2110183 50 mg
GSK2110183 50 mg capsule by mouth daily in combination with carboplatin Area Under the Curve (AUC) 5 and paclitaxel 175 mg/m2 given intravenously every 3 weeks for a maximum 6 cycles.
|
Phase 1 (Dose Escalation)-Cohort 1.5: GSK2110183 75 mg
GSK2110183 75 mg capsule by mouth daily in combination with carboplatin AUC 5 and paclitaxel 175 mg/m2 given intravenously every 3 weeks for a maximum 6 cycles.
|
Phase 1 (Dose Escalation)-Cohort 2: GSK2110183 100 mg
GSK2110183 100 mg capsule by mouth daily in combination with carboplatin AUC 5 and paclitaxel 175 mg/m2 given intravenously every 3 weeks for a maximum 6 cycles.
|
Phase 1 (Dose Escalation)-Cohort 3: GSK2110183 125 mg
GSK2110183 125 mg capsule by mouth daily in combination with carboplatin AUC 5 and paclitaxel 175 mg/m2 given intravenously every 3 weeks for a maximum 6 cycles.
|
Phase 1 (Dose Escalation)-Cohort 4: GSK2110183 150 mg
GSK2110183 150 mg capsule by mouth daily in combination with carboplatin AUC 5 and paclitaxel 175 mg/m2 given intravenously every 3 weeks for a maximum 6 cycles.
|
Phase 2 (Treatment Group): GSK2110183 125 mg (MTD)
The dosing regimen identified in Phase I will then be evaluated in Phase II, a single arm study focused on clinical efficacy. GSK2110183 125 mg (MTD) capsule by mouth daily in combination with carboplatin AUC 5 and paclitaxel 175 mg/m2 given intravenously every 3 weeks for a maximum 6 x 21 day cycles followed by continuous GSK2110183 150 mg capsule by mouth daily until progression, death or unacceptable toxicity.
|
|---|---|---|---|---|---|---|
|
Phase 1-Cohort 1: GSK2110183 50 mg
STARTED
|
4
|
0
|
0
|
0
|
0
|
0
|
|
Phase 1-Cohort 1: GSK2110183 50 mg
COMPLETED
|
4
|
0
|
0
|
0
|
0
|
0
|
|
Phase 1-Cohort 1: GSK2110183 50 mg
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Phase 1-Cohort 1.5: GSK2110183 75 mg
STARTED
|
0
|
4
|
0
|
0
|
0
|
0
|
|
Phase 1-Cohort 1.5: GSK2110183 75 mg
COMPLETED
|
0
|
3
|
0
|
0
|
0
|
0
|
|
Phase 1-Cohort 1.5: GSK2110183 75 mg
NOT COMPLETED
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Phase 1-Cohort 2: GSK2110183 100 mg
STARTED
|
0
|
0
|
6
|
0
|
0
|
0
|
|
Phase 1-Cohort 2: GSK2110183 100 mg
COMPLETED
|
0
|
0
|
4
|
0
|
0
|
0
|
|
Phase 1-Cohort 2: GSK2110183 100 mg
NOT COMPLETED
|
0
|
0
|
2
|
0
|
0
|
0
|
|
Phase 1-Cohort 3: GSK2110183 125 mg
STARTED
|
0
|
0
|
0
|
12
|
0
|
0
|
|
Phase 1-Cohort 3: GSK2110183 125 mg
COMPLETED
|
0
|
0
|
0
|
10
|
0
|
0
|
|
Phase 1-Cohort 3: GSK2110183 125 mg
NOT COMPLETED
|
0
|
0
|
0
|
2
|
0
|
0
|
|
Phase 1-Cohort 4: GSK2110183 150 mg
STARTED
|
0
|
0
|
0
|
0
|
3
|
0
|
|
Phase 1-Cohort 4: GSK2110183 150 mg
COMPLETED
|
0
|
0
|
0
|
0
|
3
|
0
|
|
Phase 1-Cohort 4: GSK2110183 150 mg
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Phase 2: GSK2110183 125 mg
STARTED
|
0
|
0
|
0
|
0
|
0
|
30
|
|
Phase 2: GSK2110183 125 mg
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
22
|
|
Phase 2: GSK2110183 125 mg
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
8
|
Reasons for withdrawal
| Measure |
Phase 1 (Dose Escalation)-Cohort 1: GSK2110183 50 mg
GSK2110183 50 mg capsule by mouth daily in combination with carboplatin Area Under the Curve (AUC) 5 and paclitaxel 175 mg/m2 given intravenously every 3 weeks for a maximum 6 cycles.
|
Phase 1 (Dose Escalation)-Cohort 1.5: GSK2110183 75 mg
GSK2110183 75 mg capsule by mouth daily in combination with carboplatin AUC 5 and paclitaxel 175 mg/m2 given intravenously every 3 weeks for a maximum 6 cycles.
|
Phase 1 (Dose Escalation)-Cohort 2: GSK2110183 100 mg
GSK2110183 100 mg capsule by mouth daily in combination with carboplatin AUC 5 and paclitaxel 175 mg/m2 given intravenously every 3 weeks for a maximum 6 cycles.
|
Phase 1 (Dose Escalation)-Cohort 3: GSK2110183 125 mg
GSK2110183 125 mg capsule by mouth daily in combination with carboplatin AUC 5 and paclitaxel 175 mg/m2 given intravenously every 3 weeks for a maximum 6 cycles.
|
Phase 1 (Dose Escalation)-Cohort 4: GSK2110183 150 mg
GSK2110183 150 mg capsule by mouth daily in combination with carboplatin AUC 5 and paclitaxel 175 mg/m2 given intravenously every 3 weeks for a maximum 6 cycles.
|
Phase 2 (Treatment Group): GSK2110183 125 mg (MTD)
The dosing regimen identified in Phase I will then be evaluated in Phase II, a single arm study focused on clinical efficacy. GSK2110183 125 mg (MTD) capsule by mouth daily in combination with carboplatin AUC 5 and paclitaxel 175 mg/m2 given intravenously every 3 weeks for a maximum 6 x 21 day cycles followed by continuous GSK2110183 150 mg capsule by mouth daily until progression, death or unacceptable toxicity.
|
|---|---|---|---|---|---|---|
|
Phase 1-Cohort 1.5: GSK2110183 75 mg
Clinical Progression
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Phase 1-Cohort 2: GSK2110183 100 mg
Adverse Event
|
0
|
0
|
2
|
0
|
0
|
0
|
|
Phase 1-Cohort 3: GSK2110183 125 mg
Clinical Progression
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Phase 1-Cohort 3: GSK2110183 125 mg
Withdrawal by Subject
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Phase 2: GSK2110183 125 mg
Adverse Event
|
0
|
0
|
0
|
0
|
0
|
1
|
|
Phase 2: GSK2110183 125 mg
Clinical Progression
|
0
|
0
|
0
|
0
|
0
|
6
|
|
Phase 2: GSK2110183 125 mg
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Dose-finding Study in Platinum-Resistant Ovarian Cancer
Baseline characteristics by cohort
| Measure |
Phase 1 (Dose Escalation): GSK2110183
n=29 Participants
GSK2110183, either at 50 mg, 75 mg, 100 mg, 125 mg or 150 mg capsule by mouth daily in combination with carboplatin AUC 5 and paclitaxel 175 mg/m2 given intravenously every 3 weeks for a maximum 6 cycles.
|
Phase 2 (Treatment Group): GSK2110183
n=30 Participants
The dosing regimen identified in Phase 1 will then be evaluated in Phase 2, a single arm study focused on clinical efficacy. GSK2110183 125 mg (MTD) capsule by mouth daily in combination with carboplatin AUC 5 and paclitaxel 175 mg/m2 given intravenously every 3 weeks for a maximum 6 x 21 day cycles followed by continuous GSK2110183 150 mg capsule by mouth daily until progression, death or unacceptable toxicity.
|
Total
n=59 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
18 - 64 years
|
18 participants
n=5 Participants
|
15 participants
n=7 Participants
|
33 participants
n=5 Participants
|
|
Age, Customized
65 - 84 years
|
11 participants
n=5 Participants
|
15 participants
n=7 Participants
|
26 participants
n=5 Participants
|
|
Sex/Gender, Customized
Female
|
29 participants
n=5 Participants
|
30 participants
n=7 Participants
|
59 participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
29 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
59 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Australia
|
13 participants
n=5 Participants
|
15 participants
n=7 Participants
|
28 participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
16 participants
n=5 Participants
|
10 participants
n=7 Participants
|
26 participants
n=5 Participants
|
|
Region of Enrollment
Russian Federation
|
0 participants
n=5 Participants
|
5 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
Height
|
160.81 cm
STANDARD_DEVIATION 6.609 • n=5 Participants
|
160.92 cm
STANDARD_DEVIATION 6.016 • n=7 Participants
|
160.86 cm
STANDARD_DEVIATION 6.264 • n=5 Participants
|
|
Weight
|
68.01 kg
STANDARD_DEVIATION 15.847 • n=5 Participants
|
69.45 kg
STANDARD_DEVIATION 15.836 • n=7 Participants
|
68.74 kg
STANDARD_DEVIATION 15.721 • n=5 Participants
|
PRIMARY outcome
Timeframe: Up to Week 3Population: All Treated Subjects (ATS) in Phase 1.
Outcome measures
| Measure |
Phase 1 (Dose Escalation): GSK2110183
n=29 Participants
GSK2110183, either at 50 mg, 75 mg, 100 mg, 125 mg or 150 mg capsule by mouth daily in combination with carboplatin AUC 5 and paclitaxel 175 mg/m2 given intravenously every 3 weeks for a maximum 6 cycles.
|
|---|---|
|
Phase 1: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade Greater Than or Equal to (≥) 3 in Severity
Subjects with at Least 1 TEAE of Grade ≥3
|
26 Participants
|
|
Phase 1: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade Greater Than or Equal to (≥) 3 in Severity
Neutropenia
|
12 Participants
|
|
Phase 1: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade Greater Than or Equal to (≥) 3 in Severity
Hypomagnesaemia
|
6 Participants
|
|
Phase 1: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade Greater Than or Equal to (≥) 3 in Severity
Diarrhoea
|
1 Participants
|
|
Phase 1: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade Greater Than or Equal to (≥) 3 in Severity
Rash Maculo-Papular
|
2 Participants
|
|
Phase 1: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade Greater Than or Equal to (≥) 3 in Severity
Vomiting
|
2 Participants
|
|
Phase 1: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade Greater Than or Equal to (≥) 3 in Severity
Anaemia
|
3 Participants
|
|
Phase 1: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade Greater Than or Equal to (≥) 3 in Severity
Rash
|
2 Participants
|
|
Phase 1: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade Greater Than or Equal to (≥) 3 in Severity
Fatigue
|
1 Participants
|
|
Phase 1: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade Greater Than or Equal to (≥) 3 in Severity
Nausea
|
3 Participants
|
|
Phase 1: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade Greater Than or Equal to (≥) 3 in Severity
Neutropenic sepsis
|
1 Participants
|
|
Phase 1: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade Greater Than or Equal to (≥) 3 in Severity
Hyperglycemia
|
3 Participants
|
PRIMARY outcome
Timeframe: Up to Week 3Population: ATS population (Phase 1)
Study Treatment refers to GSK2110183 with or without Carboplatin and/or Paclitaxel. Dose limiting toxicity (DLT): An event is considered a DLT if it had a reasonable causal relationship to study drug \& occurs within first 3 weeks of therapy \& met at least one of the following criteria: * Grade 3 or 4 non-hematologic toxicity as described in the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.0, 2009 \[NCI, 2009\] with the exceptions of Grade 3 electrolyte disturbances that respond to correction within 24 hours; or Grade 3 rash, diarrhea, nausea, vomiting and mucositis that responded to standard medical supportive care within 48 hours). * Grade 4 neutropenia lasting ≥5 days * Febrile neutropenia * Grade 3 thrombocytopenia with bleeding * Grade 4 thrombocytopenia * Grade 4 anemia * Treatment delay of \>14 days due to unresolved toxicity * Alanine aminotransferase (ALT) \>3 times upper limit of normal (ULN) with bilirubin \>2 times ULN
Outcome measures
| Measure |
Phase 1 (Dose Escalation): GSK2110183
n=29 Participants
GSK2110183, either at 50 mg, 75 mg, 100 mg, 125 mg or 150 mg capsule by mouth daily in combination with carboplatin AUC 5 and paclitaxel 175 mg/m2 given intravenously every 3 weeks for a maximum 6 cycles.
|
|---|---|
|
Phase 1 Safety: Number of Subjects Reporting Adverse Events
Treatment Emergent Adverse Events (TEAEs)
|
29 participants
|
|
Phase 1 Safety: Number of Subjects Reporting Adverse Events
Serious TEAEs
|
14 participants
|
|
Phase 1 Safety: Number of Subjects Reporting Adverse Events
GSK2110183 Related Serious TEAEs
|
7 participants
|
|
Phase 1 Safety: Number of Subjects Reporting Adverse Events
GSK2110183 Related TEAEs
|
29 participants
|
|
Phase 1 Safety: Number of Subjects Reporting Adverse Events
Study Treatment Related TEAEs
|
29 participants
|
|
Phase 1 Safety: Number of Subjects Reporting Adverse Events
TEAEs Leading to Discontinuation of GSK2110183
|
6 participants
|
|
Phase 1 Safety: Number of Subjects Reporting Adverse Events
TEAEs Leading to Discontinuation of Study Treatmnt
|
17 participants
|
|
Phase 1 Safety: Number of Subjects Reporting Adverse Events
TEAEs Leading to Dose Modification of GSK2110183
|
18 participants
|
|
Phase 1 Safety: Number of Subjects Reporting Adverse Events
TEAEs Leading to Dose Modification of Study Trtmnt
|
26 participants
|
|
Phase 1 Safety: Number of Subjects Reporting Adverse Events
TEAEs Leading to Death
|
0 participants
|
|
Phase 1 Safety: Number of Subjects Reporting Adverse Events
Dose Limiting Toxicity
|
3 participants
|
PRIMARY outcome
Timeframe: Up to Week 3Population: ATS population (Phase 1).
MTD is defined as the highest dose at which 1 or fewer of up to 6 subjects experience a dose limiting toxicity (DLT) during the first 3 weeks of combination therapy. MTD was considered exceeded if 2 or more subjects in a cohort of up to 6 subjects experienced a DLT.
Outcome measures
| Measure |
Phase 1 (Dose Escalation): GSK2110183
n=29 Participants
GSK2110183, either at 50 mg, 75 mg, 100 mg, 125 mg or 150 mg capsule by mouth daily in combination with carboplatin AUC 5 and paclitaxel 175 mg/m2 given intravenously every 3 weeks for a maximum 6 cycles.
|
|---|---|
|
Phase 1: Maximum Tolerated Dose (MTD) of GSK2110183
|
125 mg
|
PRIMARY outcome
Timeframe: Every 3 weeks up to 6 monthsPopulation: ATS population (Phase 2-Cohort A)
Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST) 1.1 criteria for target lesions and assessed by MRI: Complete Response (CR) is Disappearance of all target lesions and Partial Response (PR) is greater than or equal to (≥) 30% decrease in the sum of the longest diameter of target lesions. Overall Response (OR) = CR + PR.
Outcome measures
| Measure |
Phase 1 (Dose Escalation): GSK2110183
n=28 Participants
GSK2110183, either at 50 mg, 75 mg, 100 mg, 125 mg or 150 mg capsule by mouth daily in combination with carboplatin AUC 5 and paclitaxel 175 mg/m2 given intravenously every 3 weeks for a maximum 6 cycles.
|
|---|---|
|
Overall Response Rate (ORR) in Phase 2 Subjects With Recurrent Platinum-resistant Ovarian Cancer (Cohort A)
Complete Response
|
7.1 Percentage of participants
|
|
Overall Response Rate (ORR) in Phase 2 Subjects With Recurrent Platinum-resistant Ovarian Cancer (Cohort A)
Partial Response
|
25.0 Percentage of participants
|
|
Overall Response Rate (ORR) in Phase 2 Subjects With Recurrent Platinum-resistant Ovarian Cancer (Cohort A)
Stable Disease
|
39.3 Percentage of participants
|
|
Overall Response Rate (ORR) in Phase 2 Subjects With Recurrent Platinum-resistant Ovarian Cancer (Cohort A)
Progressive Disease
|
14.3 Percentage of participants
|
|
Overall Response Rate (ORR) in Phase 2 Subjects With Recurrent Platinum-resistant Ovarian Cancer (Cohort A)
Not Evaluable
|
14.3 Percentage of participants
|
|
Overall Response Rate (ORR) in Phase 2 Subjects With Recurrent Platinum-resistant Ovarian Cancer (Cohort A)
Overall Response Rate
|
32.1 Percentage of participants
|
PRIMARY outcome
Timeframe: Every 3 weeks up to 6 monthsPopulation: As described in SAP (dated 14-Jul-2015), data was not analyzed separately for Cohort B (n=2) as there were \<10 subjects in this group due to difficulty in enrolling Platinum-refractory ovarian cancer subjects.
Per RECIST version 1.1 criteria for target lesions and assessed by MRI: Complete Response (CR) is Disappearance of all target lesions and Partial Response (PR) is ≥30% decrease in the sum of the longest diameter of target lesions. Overall Response (OR) = CR + PR.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to Week 3Population: ATS population (Phase 1)
Per RECIST version 1.1 criteria for target lesions and assessed by MRI: Complete Response (CR) is disappearance of all target lesions and Partial Response (PR) is ≥30% decrease in the sum of the longest diameter of target lesions. Overall Response (OR) = CR + PR.
Outcome measures
| Measure |
Phase 1 (Dose Escalation): GSK2110183
n=29 Participants
GSK2110183, either at 50 mg, 75 mg, 100 mg, 125 mg or 150 mg capsule by mouth daily in combination with carboplatin AUC 5 and paclitaxel 175 mg/m2 given intravenously every 3 weeks for a maximum 6 cycles.
|
|---|---|
|
ORR in Phase 1 Subjects With Recurrent Platinum-resistant Ovarian Cancer
Complete Response
|
0 Percentage of participants
|
|
ORR in Phase 1 Subjects With Recurrent Platinum-resistant Ovarian Cancer
Partial Response
|
24.1 Percentage of participants
|
|
ORR in Phase 1 Subjects With Recurrent Platinum-resistant Ovarian Cancer
Stable Disease
|
44.8 Percentage of participants
|
|
ORR in Phase 1 Subjects With Recurrent Platinum-resistant Ovarian Cancer
Progressive Disease
|
20.7 Percentage of participants
|
|
ORR in Phase 1 Subjects With Recurrent Platinum-resistant Ovarian Cancer
Not Evaluable
|
10.3 Percentage of participants
|
|
ORR in Phase 1 Subjects With Recurrent Platinum-resistant Ovarian Cancer
Overall Response Rate
|
24.1 Percentage of participants
|
SECONDARY outcome
Timeframe: Up to Day 21 (Phase 2)Population: ATS population (Phase 2)
Outcome measures
| Measure |
Phase 1 (Dose Escalation): GSK2110183
n=30 Participants
GSK2110183, either at 50 mg, 75 mg, 100 mg, 125 mg or 150 mg capsule by mouth daily in combination with carboplatin AUC 5 and paclitaxel 175 mg/m2 given intravenously every 3 weeks for a maximum 6 cycles.
|
|---|---|
|
Phase 2: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade ≥3 in Severity
Subjects with at Least 1 TEAE of Grade ≥3
|
26 participants
|
|
Phase 2: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade ≥3 in Severity
Neutropenia
|
1 participants
|
|
Phase 2: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade ≥3 in Severity
Hypomagnesaemia
|
3 participants
|
|
Phase 2: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade ≥3 in Severity
Diarrhoea
|
6 participants
|
|
Phase 2: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade ≥3 in Severity
Rash Maculo-Papular
|
5 participants
|
|
Phase 2: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade ≥3 in Severity
Vomiting
|
4 participants
|
|
Phase 2: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade ≥3 in Severity
Anaemia
|
3 participants
|
|
Phase 2: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade ≥3 in Severity
Rash
|
3 participants
|
|
Phase 2: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade ≥3 in Severity
Fatigue
|
4 participants
|
|
Phase 2: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade ≥3 in Severity
Nausea
|
1 participants
|
|
Phase 2: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade ≥3 in Severity
Neutropenic sepsis
|
3 participants
|
|
Phase 2: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade ≥3 in Severity
Hyperglycemia
|
0 participants
|
SECONDARY outcome
Timeframe: Up to Day 51Population: ATS population (Phase 2)
Dose limiting toxicity (DLT): An event is considered a DLT if it had a reasonable causal relationship to study drug \& occurs within first 3 weeks of therapy \& met at least one of the following criteria: * Grade 3 or 4 non-hematologic toxicity as described in the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.0, 2009 \[NCI, 2009\] with the exceptions of Grade 3 electrolyte disturbances that respond to correction within 24 hours; or Grade 3 rash, diarrhea, nausea, vomiting and mucositis that responded to standard medical supportive care within 48 hours). * Grade 4 neutropenia lasting ≥5 days * Febrile neutropenia * Grade 3 thrombocytopenia with bleeding * Grade 4 thrombocytopenia * Grade 4 anemia * Treatment delay of \>14 days due to unresolved toxicity * Alanine aminotransferase (ALT) \>3 times upper limit of normal (ULN) with bilirubin \>2 times ULN
Outcome measures
| Measure |
Phase 1 (Dose Escalation): GSK2110183
n=30 Participants
GSK2110183, either at 50 mg, 75 mg, 100 mg, 125 mg or 150 mg capsule by mouth daily in combination with carboplatin AUC 5 and paclitaxel 175 mg/m2 given intravenously every 3 weeks for a maximum 6 cycles.
|
|---|---|
|
Phase 2 Safety: Number of Subjects Reporting Adverse Events
TEAEs
|
30 participants
|
|
Phase 2 Safety: Number of Subjects Reporting Adverse Events
Serious TEAEs
|
16 participants
|
|
Phase 2 Safety: Number of Subjects Reporting Adverse Events
GSK2110183 Related Serious TEAEs
|
11 participants
|
|
Phase 2 Safety: Number of Subjects Reporting Adverse Events
GSK2110183 Related TEAEs
|
25 participants
|
|
Phase 2 Safety: Number of Subjects Reporting Adverse Events
Study Treatment Related TEAEs
|
30 participants
|
|
Phase 2 Safety: Number of Subjects Reporting Adverse Events
TEAEs Leading to Discontinuation of GSK2110183
|
9 participants
|
|
Phase 2 Safety: Number of Subjects Reporting Adverse Events
TEAEs Leading to Discontinuation of Study Treatmnt
|
13 participants
|
|
Phase 2 Safety: Number of Subjects Reporting Adverse Events
TEAEs Leading to Dose Modification of GSK2110183
|
17 participants
|
|
Phase 2 Safety: Number of Subjects Reporting Adverse Events
TEAEs Leading to Dose Modification of Study Trtmnt
|
24 participants
|
|
Phase 2 Safety: Number of Subjects Reporting Adverse Events
TEAEs Leading to Death
|
0 participants
|
|
Phase 2 Safety: Number of Subjects Reporting Adverse Events
Dose Limiting Toxicity
|
0 participants
|
SECONDARY outcome
Timeframe: From Month 1 to 6Population: ATS population (Phase 2)
RR is defined by the percentage of subjects with investigator-assessed Partial Cancer Antigen (CA) 125 Response (PR) or Complete CA 125 Response (CR) at any time during the study by GCIG CA 125. PR is greater than (\>) 50% decrease in CA-125 values from baseline and no clinical or radiological evidence of new lesions. CR is decrease in the CA-125 to within the normal limits and less than (\<) 40 IU/mL and no clinical or radiological evidence of disease.
Outcome measures
| Measure |
Phase 1 (Dose Escalation): GSK2110183
n=30 Participants
GSK2110183, either at 50 mg, 75 mg, 100 mg, 125 mg or 150 mg capsule by mouth daily in combination with carboplatin AUC 5 and paclitaxel 175 mg/m2 given intravenously every 3 weeks for a maximum 6 cycles.
|
|---|---|
|
Phase 2: Response Rate (RR) Defined by Gynecologic Cancer Intergroup (GCIG) CA 125
Complete CA 125 Response
|
16.7 Percentage of participants
|
|
Phase 2: Response Rate (RR) Defined by Gynecologic Cancer Intergroup (GCIG) CA 125
Partial CA 125 Response
|
30.0 Percentage of participants
|
|
Phase 2: Response Rate (RR) Defined by Gynecologic Cancer Intergroup (GCIG) CA 125
Stable Response
|
30.0 Percentage of participants
|
|
Phase 2: Response Rate (RR) Defined by Gynecologic Cancer Intergroup (GCIG) CA 125
CA 125 Progression
|
0 Percentage of participants
|
|
Phase 2: Response Rate (RR) Defined by Gynecologic Cancer Intergroup (GCIG) CA 125
Not Evaluable
|
23.3 Percentage of participants
|
|
Phase 2: Response Rate (RR) Defined by Gynecologic Cancer Intergroup (GCIG) CA 125
Response rate
|
46.7 Percentage of participants
|
SECONDARY outcome
Timeframe: From first dose until disease progression or death (approximately 36 months)Population: ATS population (Phase 2-Cohort A)
PFS was defined as the number of months between date of first GSK2110183 treatment and the earliest date of disease progression by RECIST or clinical symptomatic progression or death due to any cause whichever is earlier. Progression is defined using RECIST version 1.1 as at least a 20% increase in the sum of the longest diameter of target lesion in reference to the smallest sum of the longest diameter recorded since the treatment started.
Outcome measures
| Measure |
Phase 1 (Dose Escalation): GSK2110183
n=28 Participants
GSK2110183, either at 50 mg, 75 mg, 100 mg, 125 mg or 150 mg capsule by mouth daily in combination with carboplatin AUC 5 and paclitaxel 175 mg/m2 given intravenously every 3 weeks for a maximum 6 cycles.
|
|---|---|
|
Progression Free Survival (PFS) by RECIST or Clinical Symptomatic Progression of Subjects With Recurrent Platinum-resistant Ovarian Cancer (Phase 2-Cohort A)
|
6.5 Months
Interval 4.4 to 8.1
|
SECONDARY outcome
Timeframe: From first dose until disease progression or death (approximately 36 months)Population: ATS population ((Phase 2-Cohort A)
PFS was defined as the number of months between date of first GSK2110183 treatment and the earliest date of disease progression by RECIST or death due to any cause whichever is earlier. Progression is defined using RECIST version 1.1 as at least a 20% increase in the sum of the longest diameter of target lesion in reference to the smallest sum of the longest diameter recorded since the treatment started.
Outcome measures
| Measure |
Phase 1 (Dose Escalation): GSK2110183
n=28 Participants
GSK2110183, either at 50 mg, 75 mg, 100 mg, 125 mg or 150 mg capsule by mouth daily in combination with carboplatin AUC 5 and paclitaxel 175 mg/m2 given intravenously every 3 weeks for a maximum 6 cycles.
|
|---|---|
|
PFS by RECIST of Subjects With Recurrent Platinum-resistant Ovarian Cancer (Phase 2-Cohort A)
|
7.1 Months
Interval 6.3 to 9.0
|
Adverse Events
Phase 1 (Dose Escalation): GSK2110183
Serious events: 14 serious events
Other events: 29 other events
Deaths: 0 deaths
Phase 2 (Treatment Group): GSK2110183
Serious events: 16 serious events
Other events: 30 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase 1 (Dose Escalation): GSK2110183
n=29 participants at risk
GSK2110183, either at 50 mg, 75 mg, 100 mg, 125 mg or 150 mg capsule by mouth daily in combination with carboplatin AUC 5 and paclitaxel 175 mg/m2 given intravenously every 3 weeks for a maximum 6 cycles.
|
Phase 2 (Treatment Group): GSK2110183
n=30 participants at risk
The dosing regimen identified in Phase 1 will then be evaluated in Phase 2, a single arm study focused on clinical efficacy. GSK2110183 125 mg (MTD) capsule by mouth daily in combination with carboplatin AUC 5 and paclitaxel 175 mg/m2 given intravenously every 3 weeks for a maximum 6 x 21 day cycles followed by continuous GSK2110183 150 mg capsule by mouth daily until progression, death or unacceptable toxicity.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
23.3%
7/30 • Number of events 9 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Gastrointestinal disorders
Vomiting
|
6.9%
2/29 • Number of events 3 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
6.7%
2/30 • Number of events 4 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Gastrointestinal disorders
Abdominal Pain
|
6.9%
2/29 • Number of events 3 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Gastrointestinal disorders
Nausea
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
6.7%
2/30 • Number of events 3 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Gastrointestinal disorders
Small Intestinal Obstruction
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
6.7%
2/30 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Gastrointestinal disorders
Ascites
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Gastrointestinal disorders
Colonic Obstruction
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
0.00%
0/30 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Gastrointestinal disorders
Constipation
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
0.00%
0/30 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/29 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Gastrointestinal disorders
Lip Swelling
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
0.00%
0/30 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
General disorders
Oesophageal Pain
|
0.00%
0/29 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Gastrointestinal disorders
Oesophagitis
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
0.00%
0/30 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Infections and infestations
Neutropenic Sepsis
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
6.7%
2/30 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Infections and infestations
Lower Respiratory Tract Infection
|
6.9%
2/29 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
0.00%
0/30 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Infections and infestations
Escherichia Urinary Tract Infection
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
0.00%
0/30 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Infections and infestations
Gastroenteritis Viral
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
0.00%
0/30 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Infections and infestations
Lobar Pneumonia
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
0.00%
0/30 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Infections and infestations
Oral Infection
|
0.00%
0/29 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Infections and infestations
Peritonitis Bacterial
|
0.00%
0/29 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Infections and infestations
Pneumonia
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
0.00%
0/30 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Infections and infestations
Respiratory Tract Infection Bacterial
|
0.00%
0/29 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Infections and infestations
Urinary Tract Infection
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
0.00%
0/30 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Blood and lymphatic system disorders
Anaemia
|
6.9%
2/29 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
10.0%
3/30 • Number of events 3 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
6.9%
2/29 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
6.7%
2/30 • Number of events 3 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Blood and lymphatic system disorders
Neutropenia
|
6.9%
2/29 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
0.00%
0/30 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
6.9%
2/29 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
0.00%
0/30 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
General disorders
Fatigue
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
6.7%
2/30 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
General disorders
Pyrexia
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
General disorders
Asthenia
|
0.00%
0/29 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
General disorders
Chills
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
0.00%
0/30 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
General disorders
Influenza Like Illness
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
0.00%
0/30 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
General disorders
Mucosal Inflammation
|
0.00%
0/29 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Immune system disorders
Hypersensitivity
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Immune system disorders
Drug Hypersensitivity
|
0.00%
0/29 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/29 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
0.00%
0/30 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
0.00%
0/30 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Skin and subcutaneous tissue disorders
Rash Maculo-Papular
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/29 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/29 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
0.00%
0/29 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Injury, poisoning and procedural complications
Upper Limb Fracture
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
0.00%
0/30 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Investigations
Transaminases Increased
|
0.00%
0/29 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.00%
0/29 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Nervous system disorders
Lethargy
|
0.00%
0/29 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Renal and urinary disorders
Renal Failure Acute
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
0.00%
0/30 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Vascular disorders
Hypotension
|
0.00%
0/29 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
Other adverse events
| Measure |
Phase 1 (Dose Escalation): GSK2110183
n=29 participants at risk
GSK2110183, either at 50 mg, 75 mg, 100 mg, 125 mg or 150 mg capsule by mouth daily in combination with carboplatin AUC 5 and paclitaxel 175 mg/m2 given intravenously every 3 weeks for a maximum 6 cycles.
|
Phase 2 (Treatment Group): GSK2110183
n=30 participants at risk
The dosing regimen identified in Phase 1 will then be evaluated in Phase 2, a single arm study focused on clinical efficacy. GSK2110183 125 mg (MTD) capsule by mouth daily in combination with carboplatin AUC 5 and paclitaxel 175 mg/m2 given intravenously every 3 weeks for a maximum 6 x 21 day cycles followed by continuous GSK2110183 150 mg capsule by mouth daily until progression, death or unacceptable toxicity.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
79.3%
23/29 • Number of events 45 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
60.0%
18/30 • Number of events 38 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Gastrointestinal disorders
Nausea
|
82.8%
24/29 • Number of events 53 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
50.0%
15/30 • Number of events 20 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Gastrointestinal disorders
Vomiting
|
72.4%
21/29 • Number of events 44 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
46.7%
14/30 • Number of events 22 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Gastrointestinal disorders
Constipation
|
41.4%
12/29 • Number of events 20 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
43.3%
13/30 • Number of events 14 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Gastrointestinal disorders
Gastroesophageal Reflux Disease
|
48.3%
14/29 • Number of events 25 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
20.0%
6/30 • Number of events 11 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Gastrointestinal disorders
Abdominal pain
|
41.4%
12/29 • Number of events 18 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
20.0%
6/30 • Number of events 8 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Gastrointestinal disorders
Stomatitis
|
27.6%
8/29 • Number of events 14 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
13.3%
4/30 • Number of events 4 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Gastrointestinal disorders
Dyspepsia
|
13.8%
4/29 • Number of events 6 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
23.3%
7/30 • Number of events 10 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Gastrointestinal disorders
Abdominal pain upper
|
24.1%
7/29 • Number of events 7 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
10.0%
3/30 • Number of events 3 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Gastrointestinal disorders
Abdominal distension
|
10.3%
3/29 • Number of events 3 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
10.0%
3/30 • Number of events 3 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Gastrointestinal disorders
Mouth ulceration
|
0.00%
0/29 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
20.0%
6/30 • Number of events 8 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
55.2%
16/29 • Number of events 17 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
53.3%
16/30 • Number of events 17 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Skin and subcutaneous tissue disorders
Rash
|
41.4%
12/29 • Number of events 18 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
16.7%
5/30 • Number of events 8 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
13.8%
4/29 • Number of events 5 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
33.3%
10/30 • Number of events 10 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
6.9%
2/29 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
36.7%
11/30 • Number of events 12 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
10.3%
3/29 • Number of events 4 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
6.7%
2/30 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
General disorders
Fatigue
|
65.5%
19/29 • Number of events 37 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
60.0%
18/30 • Number of events 27 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
General disorders
Oedema peripheral
|
17.2%
5/29 • Number of events 6 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
6.7%
2/30 • Number of events 4 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
General disorders
Mucosal inflammation
|
17.2%
5/29 • Number of events 6 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
General disorders
Chest pain
|
10.3%
3/29 • Number of events 5 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Metabolism and nutrition disorders
Decreased appetite
|
55.2%
16/29 • Number of events 27 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
46.7%
14/30 • Number of events 22 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
31.0%
9/29 • Number of events 10 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
26.7%
8/30 • Number of events 8 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
10.3%
3/29 • Number of events 4 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
13.3%
4/30 • Number of events 4 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
10.3%
3/29 • Number of events 4 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
10.0%
3/30 • Number of events 3 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Metabolism and nutrition disorders
Dehydration
|
10.3%
3/29 • Number of events 3 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
6.7%
2/30 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Nervous system disorders
Neuropathy peripheral
|
20.7%
6/29 • Number of events 6 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
20.0%
6/30 • Number of events 6 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Nervous system disorders
Headache
|
27.6%
8/29 • Number of events 11 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
10.0%
3/30 • Number of events 4 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
27.6%
8/29 • Number of events 11 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
6.7%
2/30 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Nervous system disorders
Dysgeusia
|
6.9%
2/29 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
13.3%
4/30 • Number of events 4 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/29 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
16.7%
5/30 • Number of events 9 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Nervous system disorders
Neurotoxicity
|
10.3%
3/29 • Number of events 4 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
6.7%
2/30 • Number of events 4 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Nervous system disorders
Dizziness
|
6.9%
2/29 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
6.7%
2/30 • Number of events 6 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/29 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
10.0%
3/30 • Number of events 3 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Nervous system disorders
Syncope
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
6.7%
2/30 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
34.5%
10/29 • Number of events 21 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
23.3%
7/30 • Number of events 8 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
31.0%
9/29 • Number of events 13 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
10.0%
3/30 • Number of events 3 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
20.7%
6/29 • Number of events 7 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
6.9%
2/29 • Number of events 4 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
13.3%
4/30 • Number of events 4 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Blood and lymphatic system disorders
Neutropenia
|
48.3%
14/29 • Number of events 19 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
16.7%
5/30 • Number of events 6 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Blood and lymphatic system disorders
Anaemia
|
10.3%
3/29 • Number of events 5 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
30.0%
9/30 • Number of events 9 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
13.8%
4/29 • Number of events 7 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
26.7%
8/30 • Number of events 11 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Infections and infestations
Upper respiratory tract infection
|
17.2%
5/29 • Number of events 5 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Infections and infestations
Oral candidiasis
|
6.9%
2/29 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
10.0%
3/30 • Number of events 4 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Infections and infestations
Lower respiratory tract infection
|
6.9%
2/29 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Infections and infestations
Urinary tract infection
|
6.9%
2/29 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
41.4%
12/29 • Number of events 16 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
10.0%
3/30 • Number of events 4 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.3%
3/29 • Number of events 3 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
6.7%
2/30 • Number of events 3 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
6.9%
2/29 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
6.7%
2/30 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Investigations
Platelet count decreased
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
13.3%
4/30 • Number of events 5 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Investigations
Alanine aminotransferase increased
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
6.7%
2/30 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Investigations
Aspartate aminotransferase increased
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
6.7%
2/30 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Investigations
Blood creatinine increased
|
6.9%
2/29 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Investigations
Weight decreased
|
6.9%
2/29 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Investigations
White blood cell count decreased
|
10.3%
3/29 • Number of events 3 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
0.00%
0/30 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Psychiatric disorders
Insomnia
|
17.2%
5/29 • Number of events 6 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
20.0%
6/30 • Number of events 6 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Vascular disorders
Hypertension
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
13.3%
4/30 • Number of events 4 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Vascular disorders
Hot flush
|
3.4%
1/29 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
6.7%
2/30 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Immune system disorders
Drug hypersensitivity
|
13.8%
4/29 • Number of events 7 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Immune system disorders
Hypersensitivity
|
3.4%
1/29 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
13.3%
4/30 • Number of events 5 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
13.8%
4/29 • Number of events 7 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Cardiac disorders
CARDIAC DISORDERS
|
6.9%
2/29 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
10.0%
3/30 • Number of events 3 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Renal and urinary disorders
RENAL AND URINARY DISORDERS
|
10.3%
3/29 • Number of events 3 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
6.7%
2/30 • Number of events 9 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Eye disorders
EYE DISORDERS
|
6.9%
2/29 • Number of events 3 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
6.7%
2/30 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
|
Reproductive system and breast disorders
REPRODUCTIVE SYSTEM AND BREAST DISORDERS
|
6.9%
2/29 • Number of events 2 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
3.3%
1/30 • Number of events 1 • Up to Day 51
Included Serious Adverse Events (SAEs) and Adverse Events (AEs) for ATS population
|
Additional Information
Study Director
Novartis Pharma AG
Phone: +41 613241111
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place