An Open-Label, Multicenter, Randomized Phase Ib/II Study of Eribulin Mesylate Administered in Combination With Gemcitabine Plus Cisplatin Versus Gemcitabine Plus Cisplatin Alone as First-Line Therapy for Locally Advanced or Metastatic Bladder Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Eisai Inc.
- 入组人数
- 92
- 主要终点
- Phase 1b: Number of Participants With Dose-limiting Toxicity (DLT) as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0
研究概览
简要总结
The purpose of this study is to determine whether Patients with Locally Advanced or Metastatic Bladder Cancer who receive Eribulin Mesylate Administered in Combination with Gemcitabine Plus Cisplatin Versus Gemcitabine Plus Cisplatin Alone as First-Line Therapy is safety and tolerable when administered to patients with locally advanced or metastatic bladder cancer and to gain preliminary data on whether patients may benefit from this combination.
详细描述
This open-label, multicenter, randomized study will consist of 2 phases:
- Phase Ib: a safety run-in period with 3 ascending doses of eribulin;
- Phase II: a randomized 2-arm design. Phase Ib Patients will be recruited into cohorts, with a minimum of 3 and a maximum of 6 patients per cohort. All patients will receive the same dose of gemcitabine (1000 mg/m2 on Days 1 and 8 of a 21-day cycle) and cisplatin (70 mg/m2 on Day 1) in combination with eribulin (administered on Days 1 and 8 of the cycle). All patients in a cohort will receive the same dose level of eribulin.
The dose level of eribulin will be escalated for additional cohorts unless greater than 2 dose limiting toxicities (DLTs) are reported at the lower dose level(s) prior to enrollment of the next dose level. If one DLT occurs at any dose level, the cohort will be expanded to include up to a maximum of 6 patients.
A Dose Escalation Committee will determine when no further dose escalation is appropriate and whether the MTD will be defined as a preceding dose or an intermediate dose.
Phase II Patients will be randomized in a 1:1 ratio to receive either eribulin in combination with gemcitabine plus cisplatin (Arm 1) or gemcitabine plus cisplatin alone (Arm 2). The eribulin dose will be 1.0 mg/m2 administered on Days 1 and 8 of each 21-day treatment cycle, the recommended Phase II dose for eribulin when administered in combination gemcitabine plus cisplatin, as determined in the Phase Ib portion of the study.
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
- None
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
E7389 in combination with gemcitabine plus cisplatin
干预措施: Gemcitabine (Drug)
E7389 in combination with gemcitabine plus cisplatin
干预措施: E7389 (Drug)
E7389 in combination with gemcitabine plus cisplatin
干预措施: Cisplatin (Drug)
gemcitabine plus cisplatin
干预措施: Gemcitabine (Drug)
gemcitabine plus cisplatin
干预措施: Cisplatin (Drug)
结局指标
主要结局
Phase 1b: Number of Participants With Dose-limiting Toxicity (DLT) as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0
时间窗: Cycle 1 (Cycle length=21 days)
DLTs were clinically significant adverse events within 21 days of treatment judged by investigator at least possibly related to treatment. This included greater than or equal to (\>=) Grade 3 (G3) peripheral neuropathy, \>=G3 nausea and vomiting despite optimal anti-emetic treatment, any other non-hematologic toxicity of \>=G3 (except alopecia, single abnormal laboratory values the Investigator judged unlikely related to study therapy, had no clinical correlate, and resolved within 7 days, and hypersensitivity reaction to any of the compounds), Grade 4 neutropenia lasting over 7 days, febrile neutropenia (defined as fever \>=38.5 degrees Celsius with absolute neutrophil count below 1.0\*10\^9 per liter, G3 thrombocytopenia with nontraumatic bleeding (without therapeutic systemic anticoagulation) requiring platelet transfusion, Grade 4 thrombocytopenia (with or without nontraumatic bleeding), any study drug-related death, any other toxicity the dose escalation committee believed to be DLT.
Phase 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
时间窗: From the first dose of study drug up to approximately 6 years 3 months
TEAE was defined as an adverse event that had an onset date, or a worsening in severity on or after the first dose of study drug up to the end of the study. Number of participants with TEAEs were reported based on safety assessments of laboratory tests, physical examination, examining bowel movements, regular measurement of vital signs, eastern cooperative oncology group-performance status and electrocardiogram parameter values. SAE was any untoward medical occurrence that at any dose: resulted in death; life threatening required inpatient hospitalization; resulted in persistent, significant disability; was congenital anomaly/birth defect or medically important due to other reasons than mentioned criteria. Number of participants with TEAEs and SAEs were reported.
次要结局
- Phase 2: Percentage of Participants With Progression-free Survival at Week 12(Week 12)
- Phase 2: Overall Survival (OS)(From the date of randomization until the date of death (Up to approximately 6 years 3 months))
- Phase 2: Progression-free Survival (PFS)(From the date of randomization until the earlier of the following two events: the date of PD or the date of death (Up to approximately 6 years 3 months))
- Phase 2: Percentage of Participants With Overall Response(From the date of randomization until CR or PR (Up to approximately 6 years 3 months))
- Phase 2: Time to Progression (TTP)(From the date of randomization until the date of PD (Up to approximately 6 years 3 months))