A Randomized, Double-blind, Placebo-controlled, Phase 2 Clinical Trial of Alisertib (MLN8237) in Combination With Paclitaxel Versus Placebo in Combination With Paclitaxel as Second Line Therapy for Small Cell Lung Cancer (SCLC).
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 178
- 主要终点
- Progression-Free Survival (PFS) as Determined by Investigator, Analyzed Using FDA Guidelines
研究概览
简要总结
This is a two-arm, randomized, double-blind, placebo-controlled, multicenter, phase 2 study designed to is to determine if the combination treatment can improve progression free survival (defined as the time from the date of randomization to the date of first documentation of disease progression or death, whichever occurs first) when compared with placebo + paclitaxel.
详细描述
The drug tested in this study is called alisertib. Alisertib is being tested to treat people who have Small Cell Lung Cancer (SCLC). This study determined the safety and efficacy for alisertib when given twice a day along with paclitaxel.
This open label study enrolled 178 patients. Participants were randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which remained undisclosed to the patient and study doctor during the study (unless there is an urgent medical need) and participants were stratified at baseline as to whether brain mets were present or not; whether they were sensitive to prior therapy or were relapsed/refractory to prior therapy; and by world region:
- Alisertib 40 mg + Paclitaxel 60 mg/m^2
- Paclitaxel 80 mg/m^2 + Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient
All participants received treatment until their disease progressed or they experienced unacceptable alisertib-related toxicity.
This multi-center trial was conducted world-wide. The overall time to participate in this study was approximately up to 22 months. Participants made multiple visits to the clinic, and were contacted by telephone every month for 6 months after the end of treatment (EOT) for follow-up assessment of progression free survival and for overall survival every 2 months until death, study closure, or 14 months after randomization of the last participant.
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
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Alisertib (MLN8237) + Paclitaxel
Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day until disease progression (Up to 17 Cycles).
干预措施: Alisertib (Drug)
Alisertib (MLN8237) + Paclitaxel
Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day until disease progression (Up to 17 Cycles).
干预措施: Paclitaxel (Drug)
Placebo + Paclitaxel
Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles).
干预措施: Placebo (Drug)
Placebo + Paclitaxel
Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles).
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) as Determined by Investigator, Analyzed Using FDA Guidelines
时间窗: Every cycle for first 6 months and then every 2 months until disease progression or death or up to data cut-off: 03 January 2016 (approximately 22 months)
PFS is defined as time in days from start of study treatment to first documentation of objective tumor progression based on Investigator's assessment or up to death due to any cause, whichever occurs first based on Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1. Progressive disease (PD) was defined as ≥20% increase in sum longest diameter (LD) in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
次要结局
- Complete Response Rate (CRR)(Baseline until disease progression, death or EOT up to data cut-off: 03 January 2016 (approximately 9.8 months))
- Duration of Response (DOR)(From first documented response until disease progression until data cut-off 03 January 2016 (approximately 9.8 months))
- Overall Survival (OS)(Contact every 2 months after EOT/disease progression until the sooner of death, study closure, or 14 months after the last participant was randomized up to data cut-off: 3 January 2016 (approximately 22 months))
- Percentage of Participants Experiencing Symptom Relief(Baseline up to Cycle 11, data cut-off: 03 January 2016 (approximately 9.8 months))
- Time to Symptom Progression(Baseline up to Cycle 11, data cut-off: 03 January 2016 (approximately 9.8 months))
- Observed Plasma Concentration for Paclitaxel(Day 1 pre-dose and 1, 2-4, 3-6, 10-11 hours post-dose; Day 8, 2 hours post-dose; Day 15, 6-9 hours post-dose)
- Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(From the first dose through 30 days after the last dose of study medication: data cut-off 03 January 2016 (Up to 10.8 months))
- Overall Response Rate (ORR)(Baseline until disease progression, death or EOT up to data cut-off: 03 January 2016 (approximately 9.8 months))
- Disease Control Rate (DCR)(Baseline until disease progression, death or EOT up to data cut-off: 03 January 2016 (approximately 9.8 months))
- Change From Baseline in Symptom (QLQ-LC13 Cough Scale, QLQ-C30 Dyspnea Scale, QLQ-C30 Pain Scale) Score at Cycle 5(Baseline up to Cycle 5 (approximately 4.6 months))
- Time to Symptom Relief(Baseline up to Cycle 11, data cut-off: 03 January 2016 (approximately 9.8 months))
- Observed Plasma Concentration for Alisertib(Day 1 pre-dose and 1, 2-4, 3-6, 10-11 hours post-dose; Day 8, 2 hours post-dose; Day 15, 6-9 hours (hrs) post-dose)