Trial Outcomes & Findings for Comparing Two Treatments for Ovarian Cancer: Standard Chemotherapy Plus Enzastaurin, or Placebo ("Sugar Pill") (NCT NCT00391118)
NCT ID: NCT00391118
Last Updated: 2020-10-19
Results Overview
PFS was defined as time from date of randomization to first date of determined progressive disease (PD) or death from any cause. PD defined using Response Evaluation Criteria in Solid Tumors (RECIST v1.0) and Gynecological Cancer Intergroup (GCIG) criteria. RECIST: ≥20% increase in sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since treatment started or appearance of ≥ 1new lesions and/or unequivocal progression of existing non-target lesions. GCIG: Cancer Antigen-125 (CA-125) serum ≥2 times upper limit of normal (ULN) for those in normal range or nadir for participants who never achieved normal range. Participants not known to have died and did not have PD were censored at last progression-free assessment. Those who received subsequent systemic anticancer therapy (after study drug discontinued) prior to determined PD or death, were censored at date of last progression-free disease assessment prior to post-discontinuation chemotherapy.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
153 participants
Primary outcome timeframe
Randomization up to date of PD or death (up to 28.6 months)
Results posted on
2020-10-19
Participant Flow
Part 1: Unblinded, single cohort safety lead-in of enzastaurin (enz) with paclitaxel (pac)/carboplatin (carb). Part 2: Randomized, double-blind, placebo-controlled trial consisting of: Baseline, Chemotherapy (start of study drug to discontinuation of pac and carb), Maintenance (day chemotherapy ends to study completion), Follow-up (up to 3 years).
Participant milestones
| Measure |
Part 1 - Modified Regimen A
Enzastaurin: 1125 milligrams (mg) loading dose on Cycle 1 Day 4 then 500 mg oral tablet, daily (QD), for six 21-day cycles on subsequent days of chemotherapy
Carboplatin: Area under the concentration time curve (AUC)5 intravenous (IV), every (q) 21 days, for six 21-day cycles of chemotherapy
Paclitaxel: 175 milligrams/square meter (mg/m²), IV, q21 days, for six 21-day cycles of chemotherapy
|
Part 2 - Regimen A
Enzastaurin: 1125 mg loading dose then 500 mg oral tablet on subsequent days, QD, for six 21-day cycles of chemotherapy and maintenance therapy up to 2 years
Carboplatin: AUC5, IV, q21 days, for six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for six 21-day cycles of chemotherapy
|
Part 2 - Regimen B
Carboplatin: AUC5, IV, q21 days for six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days for six 21-day cycles of chemotherapy
Placebo: oral tablet, QD of chemotherapy and maintenance therapy up to 2 years
|
|---|---|---|---|
|
Overall Study
STARTED
|
11
|
69
|
73
|
|
Overall Study
Received ≥1 Dose of Assigned Study Drug
|
11
|
67
|
72
|
|
Overall Study
COMPLETED
|
0
|
14
|
15
|
|
Overall Study
NOT COMPLETED
|
11
|
55
|
58
|
Reasons for withdrawal
| Measure |
Part 1 - Modified Regimen A
Enzastaurin: 1125 milligrams (mg) loading dose on Cycle 1 Day 4 then 500 mg oral tablet, daily (QD), for six 21-day cycles on subsequent days of chemotherapy
Carboplatin: Area under the concentration time curve (AUC)5 intravenous (IV), every (q) 21 days, for six 21-day cycles of chemotherapy
Paclitaxel: 175 milligrams/square meter (mg/m²), IV, q21 days, for six 21-day cycles of chemotherapy
|
Part 2 - Regimen A
Enzastaurin: 1125 mg loading dose then 500 mg oral tablet on subsequent days, QD, for six 21-day cycles of chemotherapy and maintenance therapy up to 2 years
Carboplatin: AUC5, IV, q21 days, for six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for six 21-day cycles of chemotherapy
|
Part 2 - Regimen B
Carboplatin: AUC5, IV, q21 days for six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days for six 21-day cycles of chemotherapy
Placebo: oral tablet, QD of chemotherapy and maintenance therapy up to 2 years
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
3
|
10
|
7
|
|
Overall Study
Lost to Follow-up
|
0
|
2
|
3
|
|
Overall Study
Withdrawal by Subject
|
0
|
9
|
1
|
|
Overall Study
Death
|
0
|
1
|
0
|
|
Overall Study
Physician Decision
|
0
|
3
|
0
|
|
Overall Study
Protocol Entry Criteria Not Met
|
0
|
3
|
1
|
|
Overall Study
Progressive Disease
|
7
|
26
|
43
|
|
Overall Study
Sponsor Decision
|
0
|
1
|
3
|
|
Overall Study
Protocol Violation
|
1
|
0
|
0
|
Baseline Characteristics
Comparing Two Treatments for Ovarian Cancer: Standard Chemotherapy Plus Enzastaurin, or Placebo ("Sugar Pill")
Baseline characteristics by cohort
| Measure |
Part 1 - Modified Regimen A
n=11 Participants
Enzastaurin: 1125 mg loading dose on Cycle 1 Day 4 then 500 mg oral tablet, QD, for six 21-day cycles on subsequent days of chemotherapy
Carboplatin: AUC5, IV, q21 days, for six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for six 21-day cycles of chemotherapy
|
Part 2 - Regimen A
n=69 Participants
Enzastaurin: 1125 mg loading dose then 500 mg oral tablet, QD, for up to six 21-day cycles on subsequent days of chemotherapy and maintenance therapy up to 2 years
Carboplatin: AUC5, IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
|
Part 2 - Regimen B
n=73 Participants
Carboplatin: AUC5 IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
Placebo: oral tablet, QD, of chemotherapy and maintenance therapy up to 2 years
|
Total
n=153 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
52.4 years
n=5 Participants
|
55.3 years
n=7 Participants
|
53.4 years
n=5 Participants
|
54.90 years
n=4 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
69 Participants
n=7 Participants
|
73 Participants
n=5 Participants
|
153 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
11 Participants
n=5 Participants
|
68 Participants
n=7 Participants
|
72 Participants
n=5 Participants
|
151 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
East Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
West Asian (Indian sub-continent)
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Region of Enrollment
Belgium
|
5 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
32 Participants
n=4 Participants
|
|
Region of Enrollment
Poland
|
0 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
|
Region of Enrollment
Spain
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
|
Region of Enrollment
Russia
|
0 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
37 Participants
n=4 Participants
|
|
Region of Enrollment
Germany
|
6 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
59 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Randomization up to date of PD or death (up to 28.6 months)Population: All randomized participants from Part 2 group. Participants censored for Part 2: Regimen A=38, Regimen B=35. Per protocol, Part 1 was not included as it is an open-label safety lead-in portion with PK characterization.
PFS was defined as time from date of randomization to first date of determined progressive disease (PD) or death from any cause. PD defined using Response Evaluation Criteria in Solid Tumors (RECIST v1.0) and Gynecological Cancer Intergroup (GCIG) criteria. RECIST: ≥20% increase in sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since treatment started or appearance of ≥ 1new lesions and/or unequivocal progression of existing non-target lesions. GCIG: Cancer Antigen-125 (CA-125) serum ≥2 times upper limit of normal (ULN) for those in normal range or nadir for participants who never achieved normal range. Participants not known to have died and did not have PD were censored at last progression-free assessment. Those who received subsequent systemic anticancer therapy (after study drug discontinued) prior to determined PD or death, were censored at date of last progression-free disease assessment prior to post-discontinuation chemotherapy.
Outcome measures
| Measure |
Part 2 - Regimen A
n=69 Participants
Enzastaurin: 1125 mg loading dose then 500 mg oral tablet, QD, for up to six 21-day cycles on subsequent days of chemotherapy and maintenance therapy up to 2 years
Carboplatin: AUC5, IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
|
Part 2 - Regimen B
n=73 Participants
Carboplatin: AUC5 IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
Placebo: oral tablet, QD, of chemotherapy and maintenance therapy up to 2 years
|
Part 2 - Regimen B
Carboplatin: AUC5, IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
Placebo: oral tablet, QD, of chemotherapy and maintenance therapy up to 2 years
|
|---|---|---|---|
|
Part 2: Progression-Free Survival (PFS)
|
18.9 months
Interval 13.8 to
Upper level of confidence interval not calculated due to high censoring.
|
15.2 months
Interval 11.0 to 18.9
|
—
|
SECONDARY outcome
Timeframe: Randomization to measured PD evaluated at 2 yearsPopulation: All randomized participants from Part 2 group. Participants censored for Part 2: Regimen A=38, Regimen B=35. Per protocol, Part 1 was not included as it is an open-label safety lead-in portion with PK characterization.
PFS was defined as time from date of randomization to first date of determined PD or death from any cause. PD defined using RECIST v1.0 and GCIG criteria. RECIST v1.0: as ≥20% increase in sum of LD of target lesions taking as reference the smallest sum LD recorded since treatment started or appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. GCIG: CA-125 serum ≥2 times ULN for those in normal range or nadir (the lowest value of blood counts after chemotherapy) for participants who never achieved normal range. Participants not known to have died and did not have PD were censored at last progression-free assessment. Those who received subsequent systemic anticancer therapy (after study drug discontinued) prior to determined PD or death, were censored at date of last progression-free disease assessment prior to post-discontinuation chemotherapy.
Outcome measures
| Measure |
Part 2 - Regimen A
n=69 Participants
Enzastaurin: 1125 mg loading dose then 500 mg oral tablet, QD, for up to six 21-day cycles on subsequent days of chemotherapy and maintenance therapy up to 2 years
Carboplatin: AUC5, IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
|
Part 2 - Regimen B
n=73 Participants
Carboplatin: AUC5 IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
Placebo: oral tablet, QD, of chemotherapy and maintenance therapy up to 2 years
|
Part 2 - Regimen B
Carboplatin: AUC5, IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
Placebo: oral tablet, QD, of chemotherapy and maintenance therapy up to 2 years
|
|---|---|---|---|
|
Part 2: Percentage of Participants With PFS at 2 Years
|
35.2 percentage of participants
Interval 20.4 to 50.4
|
28.2 percentage of participants
Interval 15.7 to 42.2
|
—
|
SECONDARY outcome
Timeframe: Randomization to PD or death from any cause (up to 28.6 months)Population: All randomized participants from Part 2 group, who were evaluated for tumor response. Per protocol, Part 1 was not included as it is an open-label safety lead-in portion with PK characterization.
ORR was the percentage of participants with a CR or PR using RECIST v1.0 and CA-125 GCIG criteria. RECIST v1.0: CR was defined as the disappearance of all tumors. PR was defined ≥30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD or complete disappearance of target lesions, with persistence (but not worsening) of ≥1 nontarget lesions and appearance of no new lesions. GCIG: CA-125 serum ≥2 times above ULN for those in normal range or nadir for participants who never achieved normal range. ORR calculated as: (CR + PR) / (total number of participants qualified for tumor response analysis per arm) \* 100.
Outcome measures
| Measure |
Part 2 - Regimen A
n=14 Participants
Enzastaurin: 1125 mg loading dose then 500 mg oral tablet, QD, for up to six 21-day cycles on subsequent days of chemotherapy and maintenance therapy up to 2 years
Carboplatin: AUC5, IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
|
Part 2 - Regimen B
n=18 Participants
Carboplatin: AUC5 IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
Placebo: oral tablet, QD, of chemotherapy and maintenance therapy up to 2 years
|
Part 2 - Regimen B
Carboplatin: AUC5, IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
Placebo: oral tablet, QD, of chemotherapy and maintenance therapy up to 2 years
|
|---|---|---|---|
|
Part 2: Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)]
|
42.9 percentage of participants
Interval 17.7 to 71.1
|
38.9 percentage of participants
Interval 17.3 to 64.3
|
—
|
SECONDARY outcome
Timeframe: Randomization to PD or death from any cause (up to 28.6 months)Population: All randomized participants from Part 2 group, who qualified for tumor response analysis. Per protocol, Part 1 was not included as it is an open-label safety lead-in portion with PK characterization.
Rate of response was defined using RECIST v1.0 and CA-125 GCIG criteria. RECIST v1.0: CR was defined as the disappearance of all target lesions. PR was defined ≥30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD or complete disappearance of target lesions, with persistence (but not worsening) of ≥1 nontarget lesions and appearance of no new lesions. SD was defined as small changes that did not meet the above criteria. PD was defined as having a ≥20% increase in the sum of the LD of target lesions. GCIG: CA-125 serum ≥2 times above ULN for those in normal range or nadir for participants who never achieved normal range. Rate of response calculated as: (CR + PR + SD)/(total number of participants qualified for tumor response analysis per arm) \*100.
Outcome measures
| Measure |
Part 2 - Regimen A
n=14 Participants
Enzastaurin: 1125 mg loading dose then 500 mg oral tablet, QD, for up to six 21-day cycles on subsequent days of chemotherapy and maintenance therapy up to 2 years
Carboplatin: AUC5, IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
|
Part 2 - Regimen B
n=18 Participants
Carboplatin: AUC5 IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
Placebo: oral tablet, QD, of chemotherapy and maintenance therapy up to 2 years
|
Part 2 - Regimen B
Carboplatin: AUC5, IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
Placebo: oral tablet, QD, of chemotherapy and maintenance therapy up to 2 years
|
|---|---|---|---|
|
Part 2: Percentage of Participants With CR or PR or Stable Disease (SD) (Rate of Response)
CR
|
7.1 percentage of participants
Interval 0.2 to 33.9
|
22.2 percentage of participants
Interval 6.4 to 47.6
|
—
|
|
Part 2: Percentage of Participants With CR or PR or Stable Disease (SD) (Rate of Response)
PR
|
35.7 percentage of participants
Interval 12.8 to 64.9
|
16.7 percentage of participants
Interval 3.6 to 41.4
|
—
|
|
Part 2: Percentage of Participants With CR or PR or Stable Disease (SD) (Rate of Response)
SD
|
42.9 percentage of participants
Interval 17.7 to 71.1
|
50.0 percentage of participants
Interval 26.0 to 74.0
|
—
|
SECONDARY outcome
Timeframe: Randomization up to date of PD or death (up to 28.6 months)Population: All randomized participants (Pts) from Part 2 group. Pts censored: Regimens A/B (A/B)-High (H), Low (L) Expression: PKCβ2 Cytoplasm (Cyto) (H4/5,L26/22), PTEN Cyto (H24/24, L6/3), PTEN Membrane (H9/8, L21/19), PTEN Nucleus (H13/6, L17/21), pCREB Nucleus (H14/10, L16/17), pGSK3b Cyto (H7/3, L22/23), pS6 Cyto (H21/18, L9/9).
PE measured using Immunohistochemistry (IHC) assay, scored 0 (negative, no staining) to 3+ (brightest staining). IHC H-scores for protein biomarkers (PKCβ2, PTEN, pCREB, pGSK3b, pS6) calculated as: \[1\*(percentage of cells stained \[PCS\] as 1+)\]+\[2\*(PCS as 2+)\]+\[3\*(PCS as 3+)\]. High PE: ≥marker threshold value and Low PE: \<marker threshold value. PFS: date of randomization to PD or death. PD defined using RECIST v1.0 and GCIG criteria. RECIST: ≥20% increase in sum of LD of target lesions taking as references smallest sum LD recorded since treatment started or appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. GCIG: CA-125 serum ≥2 times ULN for those in normal range or nadir for those who never achieved normal range. Per protocol, Part 1 was not included as it is an open-label safety lead-in portion with PK characterization.
Outcome measures
| Measure |
Part 2 - Regimen A
n=56 Participants
Enzastaurin: 1125 mg loading dose then 500 mg oral tablet, QD, for up to six 21-day cycles on subsequent days of chemotherapy and maintenance therapy up to 2 years
Carboplatin: AUC5, IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
|
Part 2 - Regimen B
n=55 Participants
Carboplatin: AUC5 IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
Placebo: oral tablet, QD, of chemotherapy and maintenance therapy up to 2 years
|
Part 2 - Regimen B
Carboplatin: AUC5, IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
Placebo: oral tablet, QD, of chemotherapy and maintenance therapy up to 2 years
|
|---|---|---|---|
|
Part 2: Translational Research: PFS Based on Protein Expression (PE) (To Assess Biological Markers in Tumors That Could Indicate Who Could Benefit From Enzastaurin Treatment)
PKCβ2 Cytoplasm High Expression (H≥115)
|
18.9 months
Interval 12.8 to
Upper limit of Confidence Interval was not reached.
|
10.4 months
Interval 8.0 to 18.0
|
—
|
|
Part 2: Translational Research: PFS Based on Protein Expression (PE) (To Assess Biological Markers in Tumors That Could Indicate Who Could Benefit From Enzastaurin Treatment)
PKCβ2 Cytoplasm Low Expression (H<115)
|
19.1 months
Interval 12.1 to
Upper limit of Confidence Interval was not reached.
|
18.2 months
Interval 13.3 to
Upper limit of Confidence Interval was not reached.
|
—
|
|
Part 2: Translational Research: PFS Based on Protein Expression (PE) (To Assess Biological Markers in Tumors That Could Indicate Who Could Benefit From Enzastaurin Treatment)
PTEN Cytoplasm High Expression (H≥50)
|
18.9 months
Interval 12.1 to 19.6
|
18.2 months
Interval 16.8 to
Upper limit of Confidence Interval was not reached.
|
—
|
|
Part 2: Translational Research: PFS Based on Protein Expression (PE) (To Assess Biological Markers in Tumors That Could Indicate Who Could Benefit From Enzastaurin Treatment)
PTEN Cytoplasm Low Expression (H<50)
|
NA months
Interval 14.0 to
Median not calculated due to high rate of censoring and Upper limit of Confidence Interval was not reached.
|
10.4 months
Interval 8.2 to 13.3
|
—
|
|
Part 2: Translational Research: PFS Based on Protein Expression (PE) (To Assess Biological Markers in Tumors That Could Indicate Who Could Benefit From Enzastaurin Treatment)
PTEN Membrane High Expression (H≥15)
|
18.4 months
Interval 10.3 to 19.6
|
NA months
Interval 11.7 to
Median not calculated due to high rate of censoring and Upper limit of Confidence Interval was not reached.
|
—
|
|
Part 2: Translational Research: PFS Based on Protein Expression (PE) (To Assess Biological Markers in Tumors That Could Indicate Who Could Benefit From Enzastaurin Treatment)
PTEN Membrane Low Expression (H<15)
|
19.1 months
Interval 10.9 to
Upper limit of Confidence Interval was not reached.
|
14.7 months
Interval 11.0 to 18.0
|
—
|
|
Part 2: Translational Research: PFS Based on Protein Expression (PE) (To Assess Biological Markers in Tumors That Could Indicate Who Could Benefit From Enzastaurin Treatment)
PTEN Nucleus High Expression (H≥12)
|
NA months
Interval 13.9 to
Median not calculated due to high rate of censoring and Upper limit of Confidence Interval was not reached.
|
16.8 months
Interval 8.7 to
Upper limit of Confidence Interval was not reached.
|
—
|
|
Part 2: Translational Research: PFS Based on Protein Expression (PE) (To Assess Biological Markers in Tumors That Could Indicate Who Could Benefit From Enzastaurin Treatment)
PTEN Nucleus Low Expression (H<12)
|
18.4 months
Interval 10.3 to 19.6
|
16.9 months
Interval 11.7 to
Upper limit of Confidence Interval was not reached.
|
—
|
|
Part 2: Translational Research: PFS Based on Protein Expression (PE) (To Assess Biological Markers in Tumors That Could Indicate Who Could Benefit From Enzastaurin Treatment)
pCREB Nucleus High Expression (H≥217)
|
19.6 months
Interval 18.4 to
Upper limit of Confidence Interval was not reached.
|
13.2 months
Interval 9.2 to
Upper limit of Confidence Interval was not reached.
|
—
|
|
Part 2: Translational Research: PFS Based on Protein Expression (PE) (To Assess Biological Markers in Tumors That Could Indicate Who Could Benefit From Enzastaurin Treatment)
pCREB Nucleus Low Expression (H<217)
|
14.0 months
Interval 10.5 to
Upper limit of Confidence Interval was not reached.
|
18.2 months
Interval 12.1 to
Upper limit of Confidence Interval was not reached.
|
—
|
|
Part 2: Translational Research: PFS Based on Protein Expression (PE) (To Assess Biological Markers in Tumors That Could Indicate Who Could Benefit From Enzastaurin Treatment)
pGSK3b Cytoplasm High Expression (H≥160)
|
NA months
Interval 18.9 to
Median not calculated due to high rate of censoring and Upper limit of Confidence Interval was not reached.
|
14.5 months
Interval 11.7 to
Upper limit of Confidence Interval was not reached.
|
—
|
|
Part 2: Translational Research: PFS Based on Protein Expression (PE) (To Assess Biological Markers in Tumors That Could Indicate Who Could Benefit From Enzastaurin Treatment)
pGSK3b Cytoplasm Low Expression (H<160)
|
14.0 months
Interval 10.3 to 19.6
|
17.4 months
Interval 11.0 to
Upper limit of Confidence Interval was not reached.
|
—
|
|
Part 2: Translational Research: PFS Based on Protein Expression (PE) (To Assess Biological Markers in Tumors That Could Indicate Who Could Benefit From Enzastaurin Treatment)
pS6 Cytoplasm High Expression (H≥105)
|
19.6 months
Interval 18.4 to
Upper limit of Confidence Interval was not reached.
|
18.0 months
Interval 11.7 to
Upper limit of Confidence Interval was not reached.
|
—
|
|
Part 2: Translational Research: PFS Based on Protein Expression (PE) (To Assess Biological Markers in Tumors That Could Indicate Who Could Benefit From Enzastaurin Treatment)
pS6 Cytoplasm Low Expression (H<105)
|
11.5 months
Interval 9.9 to 19.6
|
17.4 months
Interval 11.0 to
Upper limit of Confidence Interval was not reached.
|
—
|
SECONDARY outcome
Timeframe: Randomization up to 28.6 monthsPopulation: All enrolled (Part 1) and all randomized (Part 2) participants who received at least 1 dose of study drug according to the treatment to which the participants were assigned.
Clinically significant events were defined as SAEs and other non-serious AEs regardless of causality. A summary of SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module. The number of participants SAEs, other non-serious AEs, and those who died due to PD are included.
Outcome measures
| Measure |
Part 2 - Regimen A
n=11 Participants
Enzastaurin: 1125 mg loading dose then 500 mg oral tablet, QD, for up to six 21-day cycles on subsequent days of chemotherapy and maintenance therapy up to 2 years
Carboplatin: AUC5, IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
|
Part 2 - Regimen B
n=67 Participants
Carboplatin: AUC5 IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
Placebo: oral tablet, QD, of chemotherapy and maintenance therapy up to 2 years
|
Part 2 - Regimen B
n=72 Participants
Carboplatin: AUC5, IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
Placebo: oral tablet, QD, of chemotherapy and maintenance therapy up to 2 years
|
|---|---|---|---|
|
Number of Participants With Serious Adverse Events (SAEs), Other Non-Serious Adverse Events (AEs) and the Number of Participants Who Died (To Compare the Safety of the 2 Treatments)
SAEs
|
7 Participants
|
26 Participants
|
20 Participants
|
|
Number of Participants With Serious Adverse Events (SAEs), Other Non-Serious Adverse Events (AEs) and the Number of Participants Who Died (To Compare the Safety of the 2 Treatments)
Non-Serious AEs
|
11 Participants
|
60 Participants
|
56 Participants
|
|
Number of Participants With Serious Adverse Events (SAEs), Other Non-Serious Adverse Events (AEs) and the Number of Participants Who Died (To Compare the Safety of the 2 Treatments)
Died
|
0 Participants
|
3 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1 (carb) and Cycle 2 Day 1 (carb + enz); carb 0.25 hours (h) (prior to infusion), 0.5, 1, 2, 3, 5, and 21h after start of infusionPopulation: All enrolled participants with measurable Cmax in Part 1.
Outcome measures
| Measure |
Part 2 - Regimen A
n=10 Participants
Enzastaurin: 1125 mg loading dose then 500 mg oral tablet, QD, for up to six 21-day cycles on subsequent days of chemotherapy and maintenance therapy up to 2 years
Carboplatin: AUC5, IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
|
Part 2 - Regimen B
Carboplatin: AUC5 IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
Placebo: oral tablet, QD, of chemotherapy and maintenance therapy up to 2 years
|
Part 2 - Regimen B
Carboplatin: AUC5, IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
Placebo: oral tablet, QD, of chemotherapy and maintenance therapy up to 2 years
|
|---|---|---|---|
|
Pharmacokinetics (PK): Maximum Concentration (Cmax) for Carboplatin With and Without Enzastaurin for Part 1 of Study
Cycle 1 Day 1
|
11.1 micrograms/milliliter (µg/mL)
Geometric Coefficient of Variation 21
|
—
|
—
|
|
Pharmacokinetics (PK): Maximum Concentration (Cmax) for Carboplatin With and Without Enzastaurin for Part 1 of Study
Cycle 2 Day 1
|
10.8 micrograms/milliliter (µg/mL)
Geometric Coefficient of Variation 13
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1 (pac) and Cycle 2 Day 1 (pac + enz); pac 1, 2, 3h (immediately after stopping infusion), 3.25, 3.5, 4, 5, 6, 8, 24, and 30h after start of infusionPopulation: All enrolled participants with measurable Cmax for pac in Part 1.
Outcome measures
| Measure |
Part 2 - Regimen A
n=8 Participants
Enzastaurin: 1125 mg loading dose then 500 mg oral tablet, QD, for up to six 21-day cycles on subsequent days of chemotherapy and maintenance therapy up to 2 years
Carboplatin: AUC5, IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
|
Part 2 - Regimen B
Carboplatin: AUC5 IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
Placebo: oral tablet, QD, of chemotherapy and maintenance therapy up to 2 years
|
Part 2 - Regimen B
Carboplatin: AUC5, IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
Placebo: oral tablet, QD, of chemotherapy and maintenance therapy up to 2 years
|
|---|---|---|---|
|
PK: Cmax for Paclitaxel With and Without Enzastaurin for Part 1 of Study
Cycle 1 Day 1
|
3580 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 43
|
—
|
—
|
|
PK: Cmax for Paclitaxel With and Without Enzastaurin for Part 1 of Study
Cycle 2 Day 1
|
3670 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 33
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1 (carb) and Cycle 2 Day 1 (carb + enz); carb at 0.25h (prior to infusion), 0.5, 1, 2, 3, 5, and 21h after start of infusionPopulation: All enrolled participants with measurable AUC0-∞ in Part 1.
Outcome measures
| Measure |
Part 2 - Regimen A
n=10 Participants
Enzastaurin: 1125 mg loading dose then 500 mg oral tablet, QD, for up to six 21-day cycles on subsequent days of chemotherapy and maintenance therapy up to 2 years
Carboplatin: AUC5, IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
|
Part 2 - Regimen B
Carboplatin: AUC5 IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
Placebo: oral tablet, QD, of chemotherapy and maintenance therapy up to 2 years
|
Part 2 - Regimen B
Carboplatin: AUC5, IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
Placebo: oral tablet, QD, of chemotherapy and maintenance therapy up to 2 years
|
|---|---|---|---|
|
PK: AUC From Time 0 to Infinity (AUC0-∞) for Carboplatin With and Without Enzastaurin for Part 1 of Study
Cycle 1 Day 1
|
3.32 milligrams*minute/milliliter (mg*min/mL
Geometric Coefficient of Variation 10
|
—
|
—
|
|
PK: AUC From Time 0 to Infinity (AUC0-∞) for Carboplatin With and Without Enzastaurin for Part 1 of Study
Cycle 2 Day 1
|
3.80 milligrams*minute/milliliter (mg*min/mL
Geometric Coefficient of Variation 16
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1 (pac) and Cycle 2 Day 1 (pac + enz); pac at 1, 2, 3h (immediately after stopping infusion), 3.25, 3.5, 4, 5, 6, 8, 24, and 30h after start of infusionPopulation: All enrolled participants with measurable AUC0-∞ in Part 1.
Outcome measures
| Measure |
Part 2 - Regimen A
n=8 Participants
Enzastaurin: 1125 mg loading dose then 500 mg oral tablet, QD, for up to six 21-day cycles on subsequent days of chemotherapy and maintenance therapy up to 2 years
Carboplatin: AUC5, IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
|
Part 2 - Regimen B
Carboplatin: AUC5 IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
Placebo: oral tablet, QD, of chemotherapy and maintenance therapy up to 2 years
|
Part 2 - Regimen B
Carboplatin: AUC5, IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
Placebo: oral tablet, QD, of chemotherapy and maintenance therapy up to 2 years
|
|---|---|---|---|
|
PK: AUC0-∞ for Paclitaxel With and Without Enzastaurin for Part 1 of Study
Cycle 1 Day 1
|
12000 ng*h/mL
Geometric Coefficient of Variation 24
|
—
|
—
|
|
PK: AUC0-∞ for Paclitaxel With and Without Enzastaurin for Part 1 of Study
Cycle 2 Day 1
|
14400 ng*h/mL
Geometric Coefficient of Variation 23
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 21 (enz) and Cycle 2 Day 1 (carb + pac + enz) at pre-dose, 2, 4, 6, 8 and 24h after the enz dosePopulation: All enrolled participants with measurable Cmax,ss in Part 1.
Cmax,ss for enzastaurin, its metabolite LSN326020 (LY326020) and total analytes are reported.
Outcome measures
| Measure |
Part 2 - Regimen A
n=9 Participants
Enzastaurin: 1125 mg loading dose then 500 mg oral tablet, QD, for up to six 21-day cycles on subsequent days of chemotherapy and maintenance therapy up to 2 years
Carboplatin: AUC5, IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
|
Part 2 - Regimen B
Carboplatin: AUC5 IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
Placebo: oral tablet, QD, of chemotherapy and maintenance therapy up to 2 years
|
Part 2 - Regimen B
Carboplatin: AUC5, IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
Placebo: oral tablet, QD, of chemotherapy and maintenance therapy up to 2 years
|
|---|---|---|---|
|
PK: Cmax at Steady State (Cmax,ss) for Part 1 of Study
Enzastaurin Cycle 1 Day 21
|
1230 nmol/L
Geometric Coefficient of Variation 110
|
—
|
—
|
|
PK: Cmax at Steady State (Cmax,ss) for Part 1 of Study
Enzastaurin Cycle 2 Day 1
|
935 nmol/L
Geometric Coefficient of Variation 80
|
—
|
—
|
|
PK: Cmax at Steady State (Cmax,ss) for Part 1 of Study
LSN326020 Cycle 1 Day 21
|
890 nmol/L
Geometric Coefficient of Variation 58
|
—
|
—
|
|
PK: Cmax at Steady State (Cmax,ss) for Part 1 of Study
LSN326020 Cycle 2 Day1
|
814 nmol/L
Geometric Coefficient of Variation 30
|
—
|
—
|
|
PK: Cmax at Steady State (Cmax,ss) for Part 1 of Study
Total Analyte Cycle 1 Day 21
|
2190 nmol/L
Geometric Coefficient of Variation 81
|
—
|
—
|
|
PK: Cmax at Steady State (Cmax,ss) for Part 1 of Study
Total Analyte Cycle 2 Day 1
|
1640 nmol/L
Geometric Coefficient of Variation 57
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 2 Day 1 (carb + pac + enz) at pre-dose, 2, 4, 6, 8 and 24h after the enz dosePopulation: All randomized participants with measurable AUCτ,ss in Part 2.
AUCτ,ss for enzastaurin, its metabolite LSN326020 (LY326020), and total analytes are reported.
Outcome measures
| Measure |
Part 2 - Regimen A
n=23 Participants
Enzastaurin: 1125 mg loading dose then 500 mg oral tablet, QD, for up to six 21-day cycles on subsequent days of chemotherapy and maintenance therapy up to 2 years
Carboplatin: AUC5, IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
|
Part 2 - Regimen B
Carboplatin: AUC5 IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
Placebo: oral tablet, QD, of chemotherapy and maintenance therapy up to 2 years
|
Part 2 - Regimen B
Carboplatin: AUC5, IV, q21 days, for up to six 21-day cycles of chemotherapy
Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy
Placebo: oral tablet, QD, of chemotherapy and maintenance therapy up to 2 years
|
|---|---|---|---|
|
PK: AUC During the Dosing Interval at Steady State (AUCτ,ss) for Part 2 of Study
Enzastaurin
|
47100 nmol*h/L
Geometric Coefficient of Variation 95
|
—
|
—
|
|
PK: AUC During the Dosing Interval at Steady State (AUCτ,ss) for Part 2 of Study
LSN326020
|
55600 nmol*h/L
Geometric Coefficient of Variation 47
|
—
|
—
|
|
PK: AUC During the Dosing Interval at Steady State (AUCτ,ss) for Part 2 of Study
Total Analyte
|
106000 nmol*h/L
Geometric Coefficient of Variation 63
|
—
|
—
|
Adverse Events
Part 1 - Modified Regimen A
Serious events: 7 serious events
Other events: 11 other events
Deaths: 0 deaths
Part 2 - Regimen A
Serious events: 26 serious events
Other events: 60 other events
Deaths: 0 deaths
Part 2 - Regimen B
Serious events: 20 serious events
Other events: 56 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Part 1 - Modified Regimen A
n=11 participants at risk
Enzastaurin: 1125 mg loading dose on Cycle 1 Day 4, then 500 mg oral tablet, QD, for six 21-day cycles on subsequent days of chemotherapy
Carboplatin: AUC5, IV, q21 days, for six 21-day cycles
Paclitaxel: 175 mg/m² IV, q21 days, for six 21-day cycles
|
Part 2 - Regimen A
n=67 participants at risk
Enzastaurin: 1125 mg loading dose then 500 mg, oral tablets on subsequent days, QD, for six 21-day cycles or up to 2 years
Carboplatin: AUC5, IV, q 21 days, for six 21-day cycles
Paclitaxel: 175 mg/m², IV, q21 days, for six 21-day cycles
|
Part 2 - Regimen B
n=72 participants at risk
Carboplatin: AUC5, IV, q21 days, for six 21-day cycles
Paclitaxel: 175 mg/m2² IV, q 21 days, six 21 day cycles
Placebo: oral tablet, QD
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
18.2%
2/11 • Number of events 2
|
6.0%
4/67 • Number of events 4
|
1.4%
1/72 • Number of events 2
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
9.1%
1/11 • Number of events 1
|
3.0%
2/67 • Number of events 2
|
1.4%
1/72 • Number of events 1
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/11
|
6.0%
4/67 • Number of events 7
|
0.00%
0/72
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/11
|
4.5%
3/67 • Number of events 6
|
1.4%
1/72 • Number of events 1
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/11
|
0.00%
0/67
|
1.4%
1/72 • Number of events 1
|
|
Congenital, familial and genetic disorders
Keratosis follicular
|
0.00%
0/11
|
1.5%
1/67 • Number of events 1
|
0.00%
0/72
|
|
Gastrointestinal disorders
Abdominal pain
|
9.1%
1/11 • Number of events 1
|
0.00%
0/67
|
1.4%
1/72 • Number of events 1
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/11
|
3.0%
2/67 • Number of events 3
|
2.8%
2/72 • Number of events 2
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/11
|
1.5%
1/67 • Number of events 1
|
2.8%
2/72 • Number of events 2
|
|
Gastrointestinal disorders
Diaphragmatic hernia
|
9.1%
1/11 • Number of events 1
|
0.00%
0/67
|
0.00%
0/72
|
|
Gastrointestinal disorders
Diarrhoea
|
9.1%
1/11 • Number of events 1
|
0.00%
0/67
|
0.00%
0/72
|
|
Gastrointestinal disorders
Faecaloma
|
0.00%
0/11
|
0.00%
0/67
|
1.4%
1/72 • Number of events 1
|
|
Gastrointestinal disorders
Gastrointestinal obstruction
|
9.1%
1/11 • Number of events 1
|
0.00%
0/67
|
0.00%
0/72
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/11
|
3.0%
2/67 • Number of events 2
|
1.4%
1/72 • Number of events 1
|
|
Gastrointestinal disorders
Intestinal fistula
|
9.1%
1/11 • Number of events 1
|
0.00%
0/67
|
0.00%
0/72
|
|
Gastrointestinal disorders
Large intestine perforation
|
0.00%
0/11
|
1.5%
1/67 • Number of events 1
|
0.00%
0/72
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/11
|
0.00%
0/67
|
1.4%
1/72 • Number of events 1
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/11
|
1.5%
1/67 • Number of events 1
|
2.8%
2/72 • Number of events 2
|
|
Gastrointestinal disorders
Subileus
|
9.1%
1/11 • Number of events 1
|
0.00%
0/67
|
4.2%
3/72 • Number of events 3
|
|
Gastrointestinal disorders
Umbilical hernia
|
18.2%
2/11 • Number of events 2
|
0.00%
0/67
|
1.4%
1/72 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
9.1%
1/11 • Number of events 1
|
0.00%
0/67
|
0.00%
0/72
|
|
General disorders
Asthenia
|
0.00%
0/11
|
1.5%
1/67 • Number of events 1
|
0.00%
0/72
|
|
General disorders
Fatigue
|
0.00%
0/11
|
1.5%
1/67 • Number of events 1
|
0.00%
0/72
|
|
General disorders
General physical health deterioration
|
0.00%
0/11
|
0.00%
0/67
|
1.4%
1/72 • Number of events 1
|
|
General disorders
Hernia
|
0.00%
0/11
|
1.5%
1/67 • Number of events 1
|
0.00%
0/72
|
|
General disorders
Pyrexia
|
0.00%
0/11
|
3.0%
2/67 • Number of events 2
|
0.00%
0/72
|
|
Hepatobiliary disorders
Hepatic cyst
|
0.00%
0/11
|
0.00%
0/67
|
1.4%
1/72 • Number of events 1
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.00%
0/11
|
0.00%
0/67
|
1.4%
1/72 • Number of events 1
|
|
Immune system disorders
Drug hypersensitivity
|
0.00%
0/11
|
0.00%
0/67
|
1.4%
1/72 • Number of events 1
|
|
Immune system disorders
Hypersensitivity
|
9.1%
1/11 • Number of events 1
|
0.00%
0/67
|
0.00%
0/72
|
|
Immune system disorders
Sarcoidosis
|
0.00%
0/11
|
1.5%
1/67 • Number of events 1
|
0.00%
0/72
|
|
Infections and infestations
Abdominal abscess
|
18.2%
2/11 • Number of events 2
|
0.00%
0/67
|
0.00%
0/72
|
|
Infections and infestations
Clostridial infection
|
9.1%
1/11 • Number of events 1
|
0.00%
0/67
|
0.00%
0/72
|
|
Infections and infestations
Diverticulitis
|
9.1%
1/11 • Number of events 1
|
0.00%
0/67
|
0.00%
0/72
|
|
Infections and infestations
Haematoma infection
|
0.00%
0/11
|
1.5%
1/67 • Number of events 1
|
0.00%
0/72
|
|
Infections and infestations
Lung infection
|
0.00%
0/11
|
1.5%
1/67 • Number of events 1
|
0.00%
0/72
|
|
Infections and infestations
Pseudomonas infection
|
9.1%
1/11 • Number of events 1
|
0.00%
0/67
|
0.00%
0/72
|
|
Infections and infestations
Soft tissue infection
|
0.00%
0/11
|
0.00%
0/67
|
1.4%
1/72 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/11
|
1.5%
1/67 • Number of events 1
|
2.8%
2/72 • Number of events 2
|
|
Infections and infestations
Wound infection
|
9.1%
1/11 • Number of events 1
|
0.00%
0/67
|
0.00%
0/72
|
|
Injury, poisoning and procedural complications
Forearm fracture
|
0.00%
0/11
|
1.5%
1/67 • Number of events 1
|
0.00%
0/72
|
|
Injury, poisoning and procedural complications
Lumbar vertebral fracture
|
9.1%
1/11 • Number of events 1
|
0.00%
0/67
|
0.00%
0/72
|
|
Injury, poisoning and procedural complications
Postoperative wound complication
|
0.00%
0/11
|
1.5%
1/67 • Number of events 1
|
0.00%
0/72
|
|
Injury, poisoning and procedural complications
Procedural complication
|
0.00%
0/11
|
0.00%
0/67
|
1.4%
1/72 • Number of events 1
|
|
Injury, poisoning and procedural complications
Soft tissue injury
|
9.1%
1/11 • Number of events 1
|
0.00%
0/67
|
0.00%
0/72
|
|
Injury, poisoning and procedural complications
Wound complication
|
0.00%
0/11
|
1.5%
1/67 • Number of events 2
|
0.00%
0/72
|
|
Investigations
C-reactive protein increased
|
0.00%
0/11
|
1.5%
1/67 • Number of events 1
|
0.00%
0/72
|
|
Investigations
Platelet count decreased
|
0.00%
0/11
|
1.5%
1/67 • Number of events 1
|
0.00%
0/72
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/11
|
1.5%
1/67 • Number of events 1
|
0.00%
0/72
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.00%
0/11
|
1.5%
1/67 • Number of events 1
|
0.00%
0/72
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
9.1%
1/11 • Number of events 1
|
1.5%
1/67 • Number of events 1
|
0.00%
0/72
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lipoma
|
0.00%
0/11
|
0.00%
0/67
|
1.4%
1/72 • Number of events 1
|
|
Nervous system disorders
Viith nerve paralysis
|
0.00%
0/11
|
0.00%
0/67
|
1.4%
1/72 • Number of events 1
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/11
|
1.5%
1/67 • Number of events 1
|
0.00%
0/72
|
|
Renal and urinary disorders
Ureteric perforation
|
0.00%
0/11
|
1.5%
1/67 • Number of events 1
|
0.00%
0/72
|
|
Reproductive system and breast disorders
Female genital tract fistula
|
0.00%
0/11
|
1.5%
1/67 • Number of events 1
|
0.00%
0/72
|
|
Reproductive system and breast disorders
Vaginal perforation
|
0.00%
0/11
|
1.5%
1/67 • Number of events 1
|
0.00%
0/72
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/11
|
3.0%
2/67 • Number of events 2
|
0.00%
0/72
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/11
|
1.5%
1/67 • Number of events 1
|
1.4%
1/72 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/11
|
1.5%
1/67 • Number of events 1
|
1.4%
1/72 • Number of events 1
|
|
Surgical and medical procedures
Cardiac pacemaker insertion
|
0.00%
0/11
|
0.00%
0/67
|
1.4%
1/72 • Number of events 1
|
|
Vascular disorders
Circulatory collapse
|
0.00%
0/11
|
0.00%
0/67
|
1.4%
1/72 • Number of events 1
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/11
|
3.0%
2/67 • Number of events 2
|
0.00%
0/72
|
|
Vascular disorders
Femoral artery occlusion
|
0.00%
0/11
|
1.5%
1/67 • Number of events 1
|
0.00%
0/72
|
|
Vascular disorders
Lymphocele
|
0.00%
0/11
|
3.0%
2/67 • Number of events 10
|
2.8%
2/72 • Number of events 2
|
|
Vascular disorders
Pelvic venous thrombosis
|
0.00%
0/11
|
1.5%
1/67 • Number of events 1
|
0.00%
0/72
|
Other adverse events
| Measure |
Part 1 - Modified Regimen A
n=11 participants at risk
Enzastaurin: 1125 mg loading dose on Cycle 1 Day 4, then 500 mg oral tablet, QD, for six 21-day cycles on subsequent days of chemotherapy
Carboplatin: AUC5, IV, q21 days, for six 21-day cycles
Paclitaxel: 175 mg/m² IV, q21 days, for six 21-day cycles
|
Part 2 - Regimen A
n=67 participants at risk
Enzastaurin: 1125 mg loading dose then 500 mg, oral tablets on subsequent days, QD, for six 21-day cycles or up to 2 years
Carboplatin: AUC5, IV, q 21 days, for six 21-day cycles
Paclitaxel: 175 mg/m², IV, q21 days, for six 21-day cycles
|
Part 2 - Regimen B
n=72 participants at risk
Carboplatin: AUC5, IV, q21 days, for six 21-day cycles
Paclitaxel: 175 mg/m2² IV, q 21 days, six 21 day cycles
Placebo: oral tablet, QD
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
9.1%
1/11 • Number of events 1
|
16.4%
11/67 • Number of events 20
|
16.7%
12/72 • Number of events 13
|
|
Blood and lymphatic system disorders
Leukopenia
|
9.1%
1/11 • Number of events 1
|
14.9%
10/67 • Number of events 18
|
18.1%
13/72 • Number of events 34
|
|
Blood and lymphatic system disorders
Neutropenia
|
54.5%
6/11 • Number of events 16
|
32.8%
22/67 • Number of events 62
|
37.5%
27/72 • Number of events 78
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
18.2%
2/11 • Number of events 2
|
1.5%
1/67 • Number of events 1
|
5.6%
4/72 • Number of events 5
|
|
Eye disorders
Photopsia
|
9.1%
1/11 • Number of events 1
|
0.00%
0/67
|
1.4%
1/72 • Number of events 2
|
|
Eye disorders
Vision blurred
|
9.1%
1/11 • Number of events 1
|
3.0%
2/67 • Number of events 3
|
2.8%
2/72 • Number of events 2
|
|
Gastrointestinal disorders
Abdominal distension
|
9.1%
1/11 • Number of events 1
|
1.5%
1/67 • Number of events 2
|
1.4%
1/72 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
36.4%
4/11 • Number of events 5
|
22.4%
15/67 • Number of events 27
|
22.2%
16/72 • Number of events 20
|
|
Gastrointestinal disorders
Abdominal pain upper
|
18.2%
2/11 • Number of events 5
|
14.9%
10/67 • Number of events 12
|
8.3%
6/72 • Number of events 7
|
|
Gastrointestinal disorders
Constipation
|
54.5%
6/11 • Number of events 9
|
22.4%
15/67 • Number of events 24
|
30.6%
22/72 • Number of events 34
|
|
Gastrointestinal disorders
Diarrhoea
|
54.5%
6/11 • Number of events 7
|
22.4%
15/67 • Number of events 25
|
11.1%
8/72 • Number of events 21
|
|
Gastrointestinal disorders
Dry mouth
|
9.1%
1/11 • Number of events 1
|
6.0%
4/67 • Number of events 4
|
5.6%
4/72 • Number of events 4
|
|
Gastrointestinal disorders
Dyspepsia
|
9.1%
1/11 • Number of events 1
|
3.0%
2/67 • Number of events 2
|
5.6%
4/72 • Number of events 5
|
|
Gastrointestinal disorders
Faeces discoloured
|
9.1%
1/11 • Number of events 1
|
7.5%
5/67 • Number of events 5
|
1.4%
1/72 • Number of events 1
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
18.2%
2/11 • Number of events 2
|
1.5%
1/67 • Number of events 6
|
0.00%
0/72
|
|
Gastrointestinal disorders
Gingival bleeding
|
9.1%
1/11 • Number of events 1
|
0.00%
0/67
|
0.00%
0/72
|
|
Gastrointestinal disorders
Mouth ulceration
|
9.1%
1/11 • Number of events 1
|
0.00%
0/67
|
0.00%
0/72
|
|
Gastrointestinal disorders
Nausea
|
54.5%
6/11 • Number of events 21
|
44.8%
30/67 • Number of events 77
|
48.6%
35/72 • Number of events 81
|
|
Gastrointestinal disorders
Stomatitis
|
27.3%
3/11 • Number of events 3
|
7.5%
5/67 • Number of events 5
|
5.6%
4/72 • Number of events 6
|
|
Gastrointestinal disorders
Vomiting
|
36.4%
4/11 • Number of events 11
|
23.9%
16/67 • Number of events 32
|
22.2%
16/72 • Number of events 24
|
|
General disorders
Asthenia
|
0.00%
0/11
|
7.5%
5/67 • Number of events 7
|
12.5%
9/72 • Number of events 11
|
|
General disorders
Chest pain
|
9.1%
1/11 • Number of events 1
|
1.5%
1/67 • Number of events 1
|
2.8%
2/72 • Number of events 2
|
|
General disorders
Chills
|
9.1%
1/11 • Number of events 1
|
3.0%
2/67 • Number of events 2
|
0.00%
0/72
|
|
General disorders
Fatigue
|
63.6%
7/11 • Number of events 21
|
46.3%
31/67 • Number of events 64
|
34.7%
25/72 • Number of events 66
|
|
General disorders
Mucosal inflammation
|
9.1%
1/11 • Number of events 1
|
4.5%
3/67 • Number of events 7
|
8.3%
6/72 • Number of events 12
|
|
General disorders
Oedema
|
0.00%
0/11
|
7.5%
5/67 • Number of events 8
|
1.4%
1/72 • Number of events 1
|
|
General disorders
Oedema peripheral
|
9.1%
1/11 • Number of events 1
|
4.5%
3/67 • Number of events 3
|
11.1%
8/72 • Number of events 8
|
|
General disorders
Pain
|
0.00%
0/11
|
6.0%
4/67 • Number of events 4
|
1.4%
1/72 • Number of events 1
|
|
General disorders
Pyrexia
|
63.6%
7/11 • Number of events 8
|
9.0%
6/67 • Number of events 6
|
4.2%
3/72 • Number of events 3
|
|
Infections and infestations
Clostridial infection
|
9.1%
1/11 • Number of events 1
|
0.00%
0/67
|
0.00%
0/72
|
|
Infections and infestations
Cystitis
|
9.1%
1/11 • Number of events 1
|
4.5%
3/67 • Number of events 3
|
2.8%
2/72 • Number of events 2
|
|
Infections and infestations
Herpes virus infection
|
9.1%
1/11 • Number of events 1
|
0.00%
0/67
|
2.8%
2/72 • Number of events 2
|
|
Infections and infestations
Nasopharyngitis
|
27.3%
3/11 • Number of events 3
|
7.5%
5/67 • Number of events 7
|
11.1%
8/72 • Number of events 10
|
|
Infections and infestations
Rhinitis
|
9.1%
1/11 • Number of events 1
|
3.0%
2/67 • Number of events 2
|
0.00%
0/72
|
|
Infections and infestations
Streptococcal infection
|
9.1%
1/11 • Number of events 1
|
0.00%
0/67
|
0.00%
0/72
|
|
Infections and infestations
Urinary tract infection
|
18.2%
2/11 • Number of events 2
|
7.5%
5/67 • Number of events 14
|
4.2%
3/72 • Number of events 4
|
|
Investigations
Alanine aminotransferase increased
|
9.1%
1/11 • Number of events 1
|
3.0%
2/67 • Number of events 2
|
2.8%
2/72 • Number of events 2
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/11
|
4.5%
3/67 • Number of events 3
|
6.9%
5/72 • Number of events 7
|
|
Investigations
C-reactive protein increased
|
9.1%
1/11 • Number of events 1
|
0.00%
0/67
|
0.00%
0/72
|
|
Investigations
Haemoglobin decreased
|
18.2%
2/11 • Number of events 2
|
1.5%
1/67 • Number of events 1
|
1.4%
1/72 • Number of events 1
|
|
Investigations
Platelet count decreased
|
0.00%
0/11
|
7.5%
5/67 • Number of events 7
|
4.2%
3/72 • Number of events 4
|
|
Investigations
Urine colour abnormal
|
0.00%
0/11
|
6.0%
4/67 • Number of events 4
|
1.4%
1/72 • Number of events 1
|
|
Investigations
Weight decreased
|
27.3%
3/11 • Number of events 3
|
0.00%
0/67
|
1.4%
1/72 • Number of events 1
|
|
Investigations
White blood cell count increased
|
9.1%
1/11 • Number of events 1
|
0.00%
0/67
|
1.4%
1/72 • Number of events 1
|
|
Metabolism and nutrition disorders
Decreased appetite
|
9.1%
1/11 • Number of events 2
|
4.5%
3/67 • Number of events 3
|
9.7%
7/72 • Number of events 7
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
45.5%
5/11 • Number of events 6
|
31.3%
21/67 • Number of events 29
|
29.2%
21/72 • Number of events 41
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/11
|
9.0%
6/67 • Number of events 6
|
8.3%
6/72 • Number of events 7
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
18.2%
2/11 • Number of events 4
|
3.0%
2/67 • Number of events 3
|
9.7%
7/72 • Number of events 17
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
9.1%
1/11 • Number of events 1
|
0.00%
0/67
|
0.00%
0/72
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/11
|
1.5%
1/67 • Number of events 1
|
5.6%
4/72 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
9.1%
1/11 • Number of events 1
|
1.5%
1/67 • Number of events 2
|
6.9%
5/72 • Number of events 8
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
27.3%
3/11 • Number of events 3
|
23.9%
16/67 • Number of events 31
|
20.8%
15/72 • Number of events 28
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
36.4%
4/11 • Number of events 9
|
7.5%
5/67 • Number of events 6
|
19.4%
14/72 • Number of events 17
|
|
Nervous system disorders
Dizziness
|
0.00%
0/11
|
7.5%
5/67 • Number of events 7
|
8.3%
6/72 • Number of events 6
|
|
Nervous system disorders
Dysgeusia
|
18.2%
2/11 • Number of events 2
|
9.0%
6/67 • Number of events 11
|
16.7%
12/72 • Number of events 14
|
|
Nervous system disorders
Headache
|
18.2%
2/11 • Number of events 2
|
20.9%
14/67 • Number of events 21
|
13.9%
10/72 • Number of events 20
|
|
Nervous system disorders
Neuropathy peripheral
|
0.00%
0/11
|
7.5%
5/67 • Number of events 6
|
6.9%
5/72 • Number of events 5
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/11
|
1.5%
1/67 • Number of events 1
|
11.1%
8/72 • Number of events 8
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
72.7%
8/11 • Number of events 9
|
35.8%
24/67 • Number of events 29
|
30.6%
22/72 • Number of events 27
|
|
Psychiatric disorders
Anxiety
|
9.1%
1/11 • Number of events 1
|
1.5%
1/67 • Number of events 1
|
0.00%
0/72
|
|
Psychiatric disorders
Depressed mood
|
9.1%
1/11 • Number of events 1
|
0.00%
0/67
|
1.4%
1/72 • Number of events 1
|
|
Psychiatric disorders
Insomnia
|
18.2%
2/11 • Number of events 2
|
9.0%
6/67 • Number of events 6
|
5.6%
4/72 • Number of events 4
|
|
Psychiatric disorders
Sleep disorder
|
9.1%
1/11 • Number of events 1
|
4.5%
3/67 • Number of events 3
|
1.4%
1/72 • Number of events 2
|
|
Renal and urinary disorders
Renal pain
|
9.1%
1/11 • Number of events 1
|
1.5%
1/67 • Number of events 1
|
0.00%
0/72
|
|
Renal and urinary disorders
Urinary retention
|
9.1%
1/11 • Number of events 1
|
1.5%
1/67 • Number of events 1
|
0.00%
0/72
|
|
Reproductive system and breast disorders
Breast pain
|
9.1%
1/11 • Number of events 1
|
0.00%
0/67
|
1.4%
1/72 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
9.1%
1/11 • Number of events 1
|
10.4%
7/67 • Number of events 7
|
4.2%
3/72 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/11
|
10.4%
7/67 • Number of events 8
|
9.7%
7/72 • Number of events 9
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
9.1%
1/11 • Number of events 1
|
6.0%
4/67 • Number of events 7
|
4.2%
3/72 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
81.8%
9/11 • Number of events 9
|
61.2%
41/67 • Number of events 41
|
52.8%
38/72 • Number of events 39
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
9.1%
1/11 • Number of events 1
|
6.0%
4/67 • Number of events 4
|
9.7%
7/72 • Number of events 9
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
9.1%
1/11 • Number of events 1
|
3.0%
2/67 • Number of events 2
|
4.2%
3/72 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Pain of skin
|
9.1%
1/11 • Number of events 1
|
0.00%
0/67
|
0.00%
0/72
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
18.2%
2/11 • Number of events 2
|
3.0%
2/67 • Number of events 2
|
4.2%
3/72 • Number of events 5
|
|
Skin and subcutaneous tissue disorders
Rash
|
27.3%
3/11 • Number of events 3
|
11.9%
8/67 • Number of events 11
|
11.1%
8/72 • Number of events 9
|
|
Skin and subcutaneous tissue disorders
Skin hypopigmentation
|
9.1%
1/11 • Number of events 1
|
0.00%
0/67
|
0.00%
0/72
|
|
Surgical and medical procedures
Enterostomy
|
9.1%
1/11 • Number of events 2
|
0.00%
0/67
|
1.4%
1/72 • Number of events 1
|
|
Vascular disorders
Flushing
|
9.1%
1/11 • Number of events 4
|
4.5%
3/67 • Number of events 3
|
8.3%
6/72 • Number of events 10
|
|
Vascular disorders
Hot flush
|
0.00%
0/11
|
4.5%
3/67 • Number of events 3
|
6.9%
5/72 • Number of events 5
|
|
Vascular disorders
Thrombophlebitis superficial
|
9.1%
1/11 • Number of events 1
|
0.00%
0/67
|
0.00%
0/72
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60