A Randomized, Double-blind, Placebo-Controlled, Phase 3 Study to Assess the Efficacy and Safety of Weekly Farletuzumab (MORAb-003) in Combination With Carboplatin and Taxane in Subjects With Platinum-sensitive Ovarian Cancer in First Relapse
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- Morphotek
- 入组人数
- 1,100
- 试验地点
- 342
- 主要终点
- Progression-free Survival (PFS)
研究概览
简要总结
This research is being done to find out if Carboplatin and Taxane works better alone or when given with an experimental drug called MORAb-003(farletuzumab) in subjects with first platinum sensitive relapsed ovarian cancer.
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
- •A histologically or cytologically confirmed diagnosis of non-mucinous epithelial ovarian cancer including primary peritoneal or fallopian tube malignancies
- •Must have measurable disease by CT or MRI scan
- •Must have relapsed radiologically with a randomization date within ≥6 and < 24 months of completion of first-line platinum chemotherapy
- •Have been treated with debulking surgery and first-line platinum and taxane based chemotherapy.
- •Prior bevacizumbab maintenance is allowed. The last dose of bevacizumab must have been at least 30 days before study Day
- •No cytotoxic maintenance therapy (e.g. taxane) or cancer vaccine therapy is allowed.
- •Must be a candidate for carboplatin and taxane therapy
- •Neurologic function: neuropathy (sensory and motor) ≤CTCAE Grade 1
排除标准
- •Subjects who never responded to first-line platinum-based therapy or whose first relapse occurs <6 months or >24 months from the last platinum therapy
- •Subjects who have received other therapy to treat their ovarian cancer since relapse
- •Known central nervous system (CNS) tumor involvement
- •Evidence of other active invasive malignancy requiring treatment in the past 5 years
- •Known allergic reaction to a prior monoclonal antibody therapy or have any documented HAHA
- •Previous treatment with MORAb-003 (farletuzumab)
- •Clinical contraindications to use of a taxane
研究组 & 干预措施
Farletuzumab (1.25 mg/kg)
Participants will receive farletuzumab 1.25 milligram per kilogram (mg/kg) administer as an intravenous (IV) infusion weekly, followed by taxane (paclitaxel [175 milligram per meter square {mg/m^2}] or docetaxel [75 mg/m^2]), administer as IV infusion and followed by carboplatin (to maintain area under curve [AUC] 5-6 milligram per milliliter per minute [mg/mL/minute]), administer as IV infusion, every three weeks, on Day 1 of each 21-day cycle for 6 cycles (combination therapy). Following completion of combination therapy, maintenance treatment with farletuzumab 1.25 mg/kg, administer as IV infusion, weekly is given until disease progression.
干预措施: Farletuzumab (Drug)
Farletuzumab (1.25 mg/kg)
Participants will receive farletuzumab 1.25 milligram per kilogram (mg/kg) administer as an intravenous (IV) infusion weekly, followed by taxane (paclitaxel [175 milligram per meter square {mg/m^2}] or docetaxel [75 mg/m^2]), administer as IV infusion and followed by carboplatin (to maintain area under curve [AUC] 5-6 milligram per milliliter per minute [mg/mL/minute]), administer as IV infusion, every three weeks, on Day 1 of each 21-day cycle for 6 cycles (combination therapy). Following completion of combination therapy, maintenance treatment with farletuzumab 1.25 mg/kg, administer as IV infusion, weekly is given until disease progression.
干预措施: Carboplatin (Drug)
Farletuzumab (1.25 mg/kg)
Participants will receive farletuzumab 1.25 milligram per kilogram (mg/kg) administer as an intravenous (IV) infusion weekly, followed by taxane (paclitaxel [175 milligram per meter square {mg/m^2}] or docetaxel [75 mg/m^2]), administer as IV infusion and followed by carboplatin (to maintain area under curve [AUC] 5-6 milligram per milliliter per minute [mg/mL/minute]), administer as IV infusion, every three weeks, on Day 1 of each 21-day cycle for 6 cycles (combination therapy). Following completion of combination therapy, maintenance treatment with farletuzumab 1.25 mg/kg, administer as IV infusion, weekly is given until disease progression.
干预措施: Taxane (Drug)
Farletuzumab (2.5 mg/kg)
Participants will receive farletuzumab 2.5 mg/kg administer as an IV infusion weekly, followed by taxane (paclitaxel [175 mg/m^2] or docetaxel [75 mg/m^2]), administer as IV infusion and followed by carboplatin (to maintain AUC 5-6 mg/mL/minute), administer as IV infusion, every three weeks on Day 1 of each 21-day cycle for 6 cycles (combination therapy). Following completion of combination therapy, maintenance treatment with farletuzumab 2.5 mg/kg, administer as IV infusion, weekly is given until disease progression.
干预措施: Farletuzumab (Drug)
Farletuzumab (2.5 mg/kg)
Participants will receive farletuzumab 2.5 mg/kg administer as an IV infusion weekly, followed by taxane (paclitaxel [175 mg/m^2] or docetaxel [75 mg/m^2]), administer as IV infusion and followed by carboplatin (to maintain AUC 5-6 mg/mL/minute), administer as IV infusion, every three weeks on Day 1 of each 21-day cycle for 6 cycles (combination therapy). Following completion of combination therapy, maintenance treatment with farletuzumab 2.5 mg/kg, administer as IV infusion, weekly is given until disease progression.
干预措施: Carboplatin (Drug)
Farletuzumab (2.5 mg/kg)
Participants will receive farletuzumab 2.5 mg/kg administer as an IV infusion weekly, followed by taxane (paclitaxel [175 mg/m^2] or docetaxel [75 mg/m^2]), administer as IV infusion and followed by carboplatin (to maintain AUC 5-6 mg/mL/minute), administer as IV infusion, every three weeks on Day 1 of each 21-day cycle for 6 cycles (combination therapy). Following completion of combination therapy, maintenance treatment with farletuzumab 2.5 mg/kg, administer as IV infusion, weekly is given until disease progression.
干预措施: Taxane (Drug)
Placebo
Participants will receive farletuzumab-matched placebo (0.9 percent [%] saline) administer as an IV infusion weekly, followed by taxane (paclitaxel [175 mg/m^2] or docetaxel [75 mg/m^2]), administer as IV infusion and followed by carboplatin (to maintain AUC 5-6 mg/mL/minute), administer as IV infusion, every three weeks on Day 1 of each 21-day cycle for 6 cycles (combination therapy). Following completion of combination therapy, maintenance treatment with farletuzumab-matched placebo (0.9% saline), administer as IV infusion, weekly is given until disease progression.
干预措施: Carboplatin (Drug)
Placebo
Participants will receive farletuzumab-matched placebo (0.9 percent [%] saline) administer as an IV infusion weekly, followed by taxane (paclitaxel [175 mg/m^2] or docetaxel [75 mg/m^2]), administer as IV infusion and followed by carboplatin (to maintain AUC 5-6 mg/mL/minute), administer as IV infusion, every three weeks on Day 1 of each 21-day cycle for 6 cycles (combination therapy). Following completion of combination therapy, maintenance treatment with farletuzumab-matched placebo (0.9% saline), administer as IV infusion, weekly is given until disease progression.
干预措施: Taxane (Drug)
Placebo
Participants will receive farletuzumab-matched placebo (0.9 percent [%] saline) administer as an IV infusion weekly, followed by taxane (paclitaxel [175 mg/m^2] or docetaxel [75 mg/m^2]), administer as IV infusion and followed by carboplatin (to maintain AUC 5-6 mg/mL/minute), administer as IV infusion, every three weeks on Day 1 of each 21-day cycle for 6 cycles (combination therapy). Following completion of combination therapy, maintenance treatment with farletuzumab-matched placebo (0.9% saline), administer as IV infusion, weekly is given until disease progression.
干预措施: Farletuzumab-matched placebo (Drug)
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (up to 44 months)
PFS was defined as the time (in months) from the date of randomization to the date of the first observation of progression based on the independent radiologic assessment (modified response evaluation criteria in solid tumors \[RECIST\]), or date of death, whatever the cause. As per RECIST, disease progression was defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the baseline sum of diameters of target lesions. If progression or death was not observed for a participant, the PFS time was censored at the date of the last tumor assessment without evidence of progression before the date of initiation of further antitumor treatment, or the cutoff date (whichever was earlier).
次要结局
- Percentage of Participants With Length of Second Remission Greater Than First Remission(From the date of last dose of platinum-based chemotherapy to date of relapse and date of last dose of platinum-based chemotherapy to first observation of progression (up to 48 months))
- T1/2: Terminal Half-life of Total Carboplatin and Total Paclitaxel(Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days))
- Duration of Tumor Response(From the first date of confirmed objective response (CR or PR) to first date of progression or death due to any cause (up to 48 months))
- CL: Clearance of Total Carboplatin and Total Paclitaxel(Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days))
- Overall Survival (OS)(From the date of randomization until date of death from any cause, or study termination by sponsor, whichever came first (up to 48 months))
- Cancer Antigen-125 (CA-125) Progression-Free Survival(From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (up to 44 months))
- Progression-Free Survival Based on Gynecologic Cancer InterGroup (GCIG) Criteria(From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (up to 44 months))
- Time to Tumor Response (TTR)(From the date of randomization to first documentation of objective response (up to 48 months))
- Percentage of Participants With Serologic Response (SR)(Up to 48 months)
- Time to 50% Serologic Response (TSR)(From the date of randomization to first documentation of 50% SR (up to 48 months))
- Vd: Volume of Distribution of Total Carboplatin and Total Paclitaxel(Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days))
- Mean Functional Assessment of Cancer Therapy-Ovarian Treatment Outcome Index (FACT-O TOI) Scores(Cycle 3, Cycle 6, Cycle 12 (each cycle length=21 days))
- Percentage of Participants With Objective Response(From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (up to 48 months))
- Duration of 50% Serologic Response(From the first date of documentation of response to first documentation of serologic progression or death due to any cause (up to 48 months))
- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Total Carboplatin and Total Paclitaxel(Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days))
- AUC (0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Total Carboplatin and Total Paclitaxel(Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days))
- Cmax: Maximum Observed Plasma Concentration of Total Carboplatin and Total Paclitaxel(Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days))
- Percentage of Participants With Clinical Benefit(Up to 48 months)