A Randomized, Phase 2, Placebo-Controlled, Double-Blinded Study With and Without Enzastaurin in Combination With Paclitaxel and Carboplatin as First-Line Treatment, Followed by Maintenance Treatment in Advanced Ovarian Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 153
- 试验地点
- 1
- 主要终点
- Part 2: Progression-Free Survival (PFS)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
B (Part B)
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
干预措施: paclitaxel (Drug)
A (Part A)
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
干预措施: enzastaurin (Drug)
A (Part A)
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
干预措施: carboplatin (Drug)
A (Part A)
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
干预措施: paclitaxel (Drug)
B (Part B)
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
干预措施: carboplatin (Drug)
B (Part B)
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
干预措施: placebo (Drug)
结局指标
主要结局
Part 2: Progression-Free Survival (PFS)
时间窗: 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.
次要结局
- 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))
- 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))
- 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))
- 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)
- 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)
- 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)
- 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)