A Phase 2-3, Multicenter, Randomized, Double-blind Study of Selinexor (KPT-330) Versus Placebo in Patients With Advanced Unresectable Dedifferentiated Liposarcoma (DDLS)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 342
- 试验地点
- 71
- 主要终点
- Phase 3 Double Blind: Progression-free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
研究概览
简要总结
This is a randomized, multicenter, double-blind, placebo-controlled, Phase 2-3 study of patients diagnosed with advanced unresectable dedifferentiated liposarcoma. Approximately 342 total patients will be randomized to study treatment (selinexor or placebo).
详细描述
In the Phase 2 portion of the study, 57 patients were randomized to selinexor (60 mg) or placebo at a 1:1 allocation ratio.
In the Phase 3 portion of the study, approximately 285 patients will be randomized to selinexor (60 mg) or placebo with a 2:1 allocation ratio.
Patients who progress during the blinded portion of the study will be unblinded and if receiving:
- placebo, may cross over to open-label selinexor (60mg twice-weekly)
- selinexor, will be withdrawn from further treatment and followed for survival
Study treatment will be given twice-weekly on Day 1 and Day 3 during Weeks 1-6 of each six-week (42 day) cycle until disease progression or intolerability.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients ≥12 years of age
- •Body surface area (BSA) ≥ 1.2 m2
- •Histologic evidence of DDLS at any time prior to randomization AND current evidence of DDLS requiring treatment
- •Must have measurable disease per RECIST v1.1 Response Criteria
- •Radiologic evidence of disease progression within 6 months prior to randomization. If the patient received other intervening therapy after documented disease progression, further disease progression must be documented after the completion of the intervening therapy
- •Must have had at least 2 prior lines of systemic therapy for liposarcoma (not to exceed 5 prior lines)
- •If patient received any previous systemic therapy, the last dose must have been ≥ 21 days prior to randomization (or ≥ 5 half-lives of that drug, whichever is shorter) with all clinically significant therapy-related toxicities having resolved to ≤ Grade 1
排除标准
- •Patients with pure well-differentiated liposarcoma (WDLS), myxoid/round cell or pleomorphic tumor histologic subtypes
- •Known active hepatitis B (HepB), hepatitis C (HepC) or human immunodeficiency virus (HIV) infection
- •Known central nervous system metastases
研究组 & 干预措施
Phase 2 Double-blinded: Selinexor
Participants received a fixed blinding dose of 60 milligrams (mg) selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle until progressive disease (PD).
干预措施: Selinexor (Drug)
Phase 3 Double-blinded: Selinexor
Participants received a fixed blinding dose of 60 mg selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle until PD.
干预措施: Selinexor (Drug)
Phase 2 Double-blinded: Placebo Followed by Open Label- Selinexor
Participants received a fixed blinding dose of placebo matched to selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle until PD in double-blinded treatment period. Participants in the placebo group who had PD during the Phase 2 double-blinded treatment, will be elected to cross over to open-label selinexor.
干预措施: Placebo (Drug)
Phase 3 Double-blinded: Placebo Followed by Open Label- Selinexor
Participants received a fixed blinding dose of placebo matched to selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle until PD or development of unacceptable toxicity. Participants in the placebo group who had PD during the Phase 3 double-blinded treatment, will be elected to cross over to open-label selinexor.
干预措施: Placebo (Drug)
结局指标
主要结局
Phase 3 Double Blind: Progression-free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
时间窗: From the date of randomization until the first date of disease progression, or death due to any cause whichever occurred first (up to 57 months)
PFS was defined as the time from the date of randomization until the first date of Independent Review Committee (IRC)-confirmed PD per RECIST version 1.1, or death due to any cause. PD was defined as at least a 20% increase in the sum of the longest diameter (SLD), taking as reference the smallest sum of the longest diameter (SLD) recorded from baseline or the appearance of 1 or more new lesions.
Phase 3 Open Label: Progression-free Survival (PFS) as Per RECIST Version 1.1
时间窗: From the date of randomization in the Phase 3 open label period until the first date of disease progression, or death due to any cause whichever occurred first (up to 57 months)
PFS was defined as the time from the date of randomization in the Phase 3 open-label period until the first date of IRC-confirmed PD per RECIST version 1.1, or death due to any cause. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Phase 2 Double Blind: Progression-free Survival (PFS) as Per RECIST Version 1.1
时间窗: From date of randomization until the first date of PD or death due to any cause, whichever occurred first (up to 57 months)
PFS was defined as the time from date of randomization until the first date of IRC-confirmed PD per RECIST version 1.1, or death due to any cause. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Phase 2 Open Label: Progression-free Survival (PFS) as Per RECIST Version 1.1
时间窗: From date of randomization in the Phase 2 open label period until the first date of PD or death due to any cause, whichever occurred first (up to 57 months)
PFS was defined as the time from date of randomization in the Phase 2 open-label period until the first date of IRC-confirmed PD per RECIST version 1.1, or death due to any cause. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
次要结局
- Phase 3 Open Label: Overall Survival (OS)(From date of randomization in phase 3 open label period until death due to any cause, whichever occurred first (up to 70 months))
- Phase 2 Double Blind: Overall Survival (OS)(From the date of randomization until death due to any cause, whichever occurred first (up to 70 months))
- Phase 2 Open Label: Overall Survival (OS)(From date of randomization in the Phase 2 open-label period until death due to any cause, whichever occurred first (up to 70 months))
- Phase 3 Double Blind: Time-to-Progression (TTP) as Per RECIST Version 1.1(From date of randomization until the first date of PD or death due to any cause, whichever occurred first (up to 70 months))
- Phase 3 Open Label: Time-to-Progression (TTP) as Per RECIST Version 1.1(From date of randomization in the Phase 3 open label period until the first date of PD or death due to any cause, whichever occurred first (up to 70 months))
- Phase 2 Double Blind: Time-to-Progression (TTP) as Per RECIST Version 1.1(From date of randomization until the first date of PD or death due to any cause, whichever occurred first (up to 70 months))
- Phase 2 Open Label: Time-to-Progression (TTP) as Per RECIST Version 1.1(From date of randomization in the Phase 2 open-label period until the first date of PD or death due to any cause, whichever occurred first (up to 70 months))
- Phase 3 Double Blind: Overall Response Rate (ORR)(From date of randomization until the documentation of CR or PR (up to 70 months))
- Phase 3 Open Label: Overall Response Rate (ORR)(From date of randomization in the Phase 3 open label period until the documentation of CR or PR (up to 70 months))
- Phase 2 Double Blind: Overall Response Rate (ORR)(From date of randomization until the documentation of CR or PR (up to 70 months))
- Phase 2 Open Label: Overall Response Rate (ORR)(From date of randomization in the Phase 2 open-label period until the documentation of CR or PR (up to 70 months))
- Phase 3 Double Blind: Duration of Response (DOR)(From first occurrence of CR or PR until the first date of PD (up to 70 months))
- Phase 3 Double Blind: Progression-free Survival (PFS) as Per Investigator Assessment(From the date of randomization until the first date of disease progression, or death due to any cause whichever occurred first (up to 70 months))
- Phase 3 Double Blind: Time to Next Treatment (TTNT)(Time from randomization to the first new antineoplastic therapy or death due to any cause (up to 70 months))
- Phase 2 Double Blind: Time to Next Treatment (TTNT)(Time from randomization to the first new antineoplastic therapy or death due to any cause (up to 70 months))
- Phase 3 Double Blind: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs(From start of study drug administration up to 70 months)
- Phase 3 Open Label: Number of Participants With TEAEs and Serious TEAEs(From start of study drug administration up to 70 months)
- Phase 2 Double Blind: Number of Participants With TEAEs and Serious TEAEs(From start of study drug administration up to 70 months)
- Phase 2 Open Label: Number of Participants With TEAEs and Serious TEAEs(From start of study drug administration up to 70 months)
- Phase 3 Double Blind: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30)(Baseline up to Day 1387)
- Phase 3 Open Label: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30)(Baseline up to Day 379)
- Phase 3 Double Blind: Overall Survival (OS)(From date of randomization until death due to any cause, whichever occurred first (up to 70 months))