A Randomized, Double-Blinded, Placebo-Controlled, Phase 2 Study With and Without Enzastaurin in Combination With Docetaxel and Prednisone, Followed By Enzastaurin Maintenance as First-Line Treatment in Hormone Refractory Metastatic Prostate Cancer Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 108
- 试验地点
- 1
- 主要终点
- Part 2: Percentage of Participants With Objective Tumor Response (Response Rate)
研究概览
简要总结
The purpose of the study is to compare the response rates for prostate cancer patients taking chemotherapy plus enzastaurin versus chemotherapy plus placebo.
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
- Male
- 接受健康志愿者
- 否
入选标准
- •You are at least 18 years old.
- •You live close enough to the doctor's office to attend all of your required visits.
- •You have not been treated with chemotherapy for your prostate cancer.
- •Your organs must be functioning properly.
排除标准
- •You are unable to swallow pills.
- •You have another serious illness besides your prostate cancer.
- •You have taken another experimental drug within the last 30 days.
- •You have a serious heart condition.
- •You are receiving another anti-cancer therapy.
研究组 & 干预措施
docetaxel + prednisone + enzastaurin
Regimen A: docetaxel 75 milligrams per square meter (mg/m^2), intravenous (IV) is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 milligrams (mg) oral (po), twice daily (BID) every day. In Cycle 1, enzastaurin is given as a loading dose of 1125 mg on the day prior to docetaxel and prednisone therapy, followed by enzastaurin 500 mg po, daily (QD) for the remaining Period 2 (chemotherapy) and Period 3 (maintenance).
干预措施: enzastaurin (Drug)
docetaxel + prednisone + enzastaurin
Regimen A: docetaxel 75 milligrams per square meter (mg/m^2), intravenous (IV) is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 milligrams (mg) oral (po), twice daily (BID) every day. In Cycle 1, enzastaurin is given as a loading dose of 1125 mg on the day prior to docetaxel and prednisone therapy, followed by enzastaurin 500 mg po, daily (QD) for the remaining Period 2 (chemotherapy) and Period 3 (maintenance).
干预措施: docetaxel (Drug)
docetaxel + prednisone + enzastaurin
Regimen A: docetaxel 75 milligrams per square meter (mg/m^2), intravenous (IV) is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 milligrams (mg) oral (po), twice daily (BID) every day. In Cycle 1, enzastaurin is given as a loading dose of 1125 mg on the day prior to docetaxel and prednisone therapy, followed by enzastaurin 500 mg po, daily (QD) for the remaining Period 2 (chemotherapy) and Period 3 (maintenance).
干预措施: prednisone (Drug)
docetaxel + prednisone + placebo
Regimen B: docetaxel 75 mg/m^2, IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po, BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by po, QD placebo for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
干预措施: placebo (Drug)
docetaxel + prednisone + enzastaurin (modified Regimen A)
Modified Regimen A, including pharmacokinetic (PK) characterization: Participants were treated with a modified investigational regimen with no dose escalation: docetaxel 75 mg/m2, IV was administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po, BID every day. In Cycle 1, enzastaurin was given as a loading dose of 1125 mg starting on Day 4, followed by enzastaurin 500 mg po, QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance).
干预措施: enzastaurin (Drug)
docetaxel + prednisone + enzastaurin (modified Regimen A)
Modified Regimen A, including pharmacokinetic (PK) characterization: Participants were treated with a modified investigational regimen with no dose escalation: docetaxel 75 mg/m2, IV was administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po, BID every day. In Cycle 1, enzastaurin was given as a loading dose of 1125 mg starting on Day 4, followed by enzastaurin 500 mg po, QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance).
干预措施: docetaxel (Drug)
docetaxel + prednisone + enzastaurin (modified Regimen A)
Modified Regimen A, including pharmacokinetic (PK) characterization: Participants were treated with a modified investigational regimen with no dose escalation: docetaxel 75 mg/m2, IV was administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po, BID every day. In Cycle 1, enzastaurin was given as a loading dose of 1125 mg starting on Day 4, followed by enzastaurin 500 mg po, QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance).
干预措施: prednisone (Drug)
结局指标
主要结局
Part 2: Percentage of Participants With Objective Tumor Response (Response Rate)
时间窗: Baseline up to 3 years
Response using Response Evaluation Criteria In Solid Tumors (RECIST). Complete Response (CR)=disappearance of all target lesions; Partial Response (PR)=30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD)=20% increase in sum of longest diameter of target lesions; Stable Disease (SD)=small changes that do not meet above criteria. Objective response rate (%)=number of objective responders divided by the number of participants qualified for efficacy analysis \*100, where objective responders are those participants who have met criteria either for CR or PR.
次要结局
- Prostate-Specific Androgen (PSA) Velocity at 2 Months(Baseline up to 2 months)
- Prostate-Specific Androgen (PSA) Velocity at 3 Months(Baseline up to 3 months)
- Part 2: Duration of Response(First objective response to PD/death/PSA returning to 50% or more than the original baseline value (up to 616 days))
- Percentage of Participants Exhibiting a Decline in Prostate-Specific Androgen (PSA) From Baseline ≥30% Within First 3 Months of Treatment(Baseline up to 3 months)
- Tumor Markers(Baseline up to 36 months)
- Part I: Pharmacokinetic (PK) Parameter: Maximum Observed Drug Concentration During a Dosing Interval at Steady State (Cmax,ss) of Enzastaurin, LSN326020, and Total Analyte (Enzastaurin + LSN326020)(Part 1: Cycle 1, Day 21 - predose 2, 4, 6, 8, and 24 hours postdose; Cycle 2, Day 1 - predose, 2, 3, 4, 8, and 24 hours postdose)
- Pharmacokinetic (PK) Parameter: Area Under the Concentration Versus Time Curve During 1 Dosing Interval at Steady State (AUCτ,ss) of Enzastaurin, LSN326020, and Total Analyte (Enzastaurin + LSN326020)(Part 1: Cycle 1, Day 21 - predose 2, 4, 6, 8, and 24 hours postdose; Cycle 2, Day 1 - predose, 2, 3, 4, 8, and 24 hours postdose; Part 2: Cycle 2, Day 1 - predose, 1-3, and 4-9 hours postdose)
- Pharmacokinetic (PK) Parameter: Maximum Plasma Concentration (Cmax) of Docetaxel(Part 1: Cycle 1, Day 1 - predose 0.5, 1, 1.5, 2, 3, 4, 8, and 24 hours postdose; Cycle 2, Day 1 - predose, 0.5, 1, 1.5, 2, 3, 4, 8, and 24 hours postdose)
- Part 2: Progression Free Survival (PFS)(Baseline to measured PD (up to 487 days))
- Part 2: Overall Survival (OS)(Baseline to death (up to 642 days))
- Number of Participants With Adverse Events (AEs)(Baseline through 3 years)
- Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC[0-∞]) of Docetaxel(Part 1: Cycle 1, Day 1 - predose 0.5, 1, 1.5, 2, 3, 4, 8, and 24 hours postdose; Cycle 2, Day 1 - predose, 0.5, 1, 1.5, 2, 3, 4, 8, and 24 hours postdose)