Comparing Two Treatments for Ovarian Cancer: Standard Chemotherapy Plus Enzastaurin, or Placebo ("Sugar Pill")
- Conditions
- Ovarian CancerFallopian Tube NeoplasmsPeritoneal Neoplasm
- Interventions
- Registration Number
- NCT00391118
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
Participants with ovarian cancer usually get the drugs carboplatin and paclitaxel as initial treatment. In many participants the tumor will shrink, or even disappear, after treatment with these drugs. But, unfortunately, the tumor will grow again in many participants. This trial will try to address the question: Can we delay the time till the tumor grows again by adding a 3rd drug to the standard therapy? To answer this question, participants will, by chance, either get the experimental drug enzastaurin or a "dummy pill" (placebo) during the chemotherapy and for up to 3 years after chemotherapy. Participants and physicians will not know if a participant gets enzastaurin or placebo (double-blinded trial). After a predefined time, the treatment will be uncovered, and the number of participants with tumor growth at a specific time point will be compared between the two treatments.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 153
- Participants must have specific stages of disease, known as Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stages IIB, IIC, III or IV
- Organ functions (blood, renal, liver, cardiac) must meet specific requirements.
- Participants who could become pregnant must take care not to become pregnant during the study participation and for 6 months after study discontinuation
- Participants must give written consent for study participation.
- Participants received any experimental drug within the last 30 days.
- Participants received any prior chemotherapy or other drug therapy for the current disease.
- Participants receive any other treatment for the cancer during study participation.
- Participants are unable to discontinue concurrent administration of carbamazepine, phenobarbital, or phenytoin.
- Participants are pregnant, breast feeding, or not using adequate contraceptive methods to prevent pregnancy.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description B (Part B) placebo Carboplatin: AUC5 IV, q21 days for six 21-day cycles Paclitaxel: 175 mg/m², IV, q21 days for six 21-day cycles Placebo: oral tablet B (Part B) carboplatin Carboplatin: AUC5 IV, q21 days for six 21-day cycles Paclitaxel: 175 mg/m², IV, q21 days for six 21-day cycles Placebo: oral tablet A (Part A) carboplatin Enzastaurin: 1125 milligram (mg) loading dose then 500 mg oral tablet, daily for six 21-day cycles or up to 3 years Carboplatin: Area under the concentration time curve (AUC) 5 intravenous (IV), every (q) 21 days for six 21-day cycles Paclitaxel:175 milligrams/square meter (mg/m²) IV, q21 days for six 21-day cycles A (Part A) paclitaxel Enzastaurin: 1125 milligram (mg) loading dose then 500 mg oral tablet, daily for six 21-day cycles or up to 3 years Carboplatin: Area under the concentration time curve (AUC) 5 intravenous (IV), every (q) 21 days for six 21-day cycles Paclitaxel:175 milligrams/square meter (mg/m²) IV, q21 days for six 21-day cycles A (Part A) enzastaurin Enzastaurin: 1125 milligram (mg) loading dose then 500 mg oral tablet, daily for six 21-day cycles or up to 3 years Carboplatin: Area under the concentration time curve (AUC) 5 intravenous (IV), every (q) 21 days for six 21-day cycles Paclitaxel:175 milligrams/square meter (mg/m²) IV, q21 days for six 21-day cycles B (Part B) paclitaxel Carboplatin: AUC5 IV, q21 days for six 21-day cycles Paclitaxel: 175 mg/m², IV, q21 days for six 21-day cycles Placebo: oral tablet
- Primary Outcome Measures
Name Time Method Part 2: Progression-Free Survival (PFS) Randomization up to date of PD or death (up to 28.6 months) 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.
- Secondary Outcome Measures
Name Time Method Part 2: Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)] Randomization to PD or death from any cause (up to 28.6 months) 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.
Part 2: Percentage of Participants With CR or PR or Stable Disease (SD) (Rate of Response) Randomization to PD or death from any cause (up to 28.6 months) 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.
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) Randomization up to date of PD or death (up to 28.6 months) 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.
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) Randomization up to 28.6 months 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.
Pharmacokinetics (PK): Maximum Concentration (Cmax) for Carboplatin With and Without Enzastaurin for Part 1 of Study 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 Part 2: Percentage of Participants With PFS at 2 Years Randomization to measured PD evaluated 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.
PK: Cmax for Paclitaxel With and Without Enzastaurin for Part 1 of Study 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 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 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 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 Cmax,ss for enzastaurin, its metabolite LSN326020 (LY326020) and total analytes are reported.
PK: AUC During the Dosing Interval at Steady State (AUCτ,ss) for Part 2 of Study Cycle 2 Day 1 (carb + pac + enz) at pre-dose, 2, 4, 6, 8 and 24h after the enz dose AUCτ,ss for enzastaurin, its metabolite LSN326020 (LY326020), and total analytes are reported.
Trial Locations
- Locations (1)
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
🇪🇸Valencia, Spain