Comparing Two Treatments for Ovarian Cancer: Standard Chemotherapy Plus Enzastaurin, or Placebo ("Sugar Pill")

Part 2: Percentage of Participants With PFS at 2 Years

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.

Time frame: Randomization to measured PD evaluated at 2 years

Part 2: Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)]

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.

Time frame: Randomization to PD or death from any cause (up to 28.6 months)

Part 2: Percentage of Participants With CR or PR or Stable Disease (SD) (Rate of Response)

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.

Time frame: Randomization to PD or death from any cause (up to 28.6 months)

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)

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.

Time frame: Randomization up to date of PD or death (up to 28.6 months)

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)

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.

Time frame: Randomization up to 28.6 months

Pharmacokinetics (PK): Maximum Concentration (Cmax) for Carboplatin With and Without Enzastaurin for Part 1 of Study

Time frame: 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 infusion

PK: Cmax for Paclitaxel With and Without Enzastaurin for Part 1 of Study

Time frame: 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 infusion

PK: AUC From Time 0 to Infinity (AUC0-∞) for Carboplatin With and Without Enzastaurin for Part 1 of Study

Time frame: 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 infusion

PK: AUC0-∞ for Paclitaxel With and Without Enzastaurin for Part 1 of Study

Time frame: 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 infusion

PK: Cmax at Steady State (Cmax,ss) for Part 1 of Study

Cmax,ss for enzastaurin, its metabolite LSN326020 (LY326020) and total analytes are reported.

Time frame: 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 dose

PK: AUC During the Dosing Interval at Steady State (AUCτ,ss) for Part 2 of Study

AUCτ,ss for enzastaurin, its metabolite LSN326020 (LY326020), and total analytes are reported.

Time frame: Cycle 2 Day 1 (carb + pac + enz) at pre-dose, 2, 4, 6, 8 and 24h after the enz dose