A Phase 2, Randomized, Open-Label Study Of Bosutinib Administered In Combination With Exemestane Versus Exemestane Alone As Second Line Therapy In Postmenopausal Women With Locally Advanced Or Metastatic ER+/PgR+/ErbB2- Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Progression Free Survival (PFS) Based on Independent Radiologist
研究概览
简要总结
This is a phase 2, open-label, multicenter, 2-arm study of bosutinib administered in combination with exemestane versus exemestane alone. This is a 2-part study consisting of a safety lead-in phase and randomized phase 2 portion. Subjects in part 1 will receive bosutinib and exemestane daily, and will be closely monitored for 28 days. If no safety concerns arise, then future eligible subjects will be randomly assigned to the main phase of the study. They will either receive bosutinib daily combined with daily exemestane, or daily exemestane alone for a specified period of time. Subjects will be followed up for survival after treatment discontinuation.
详细描述
This study was terminated on 19 Apr 2010 due to unfavorable risk benefit ratio which did not support continuation in part 2 of the study. Even if the safety profile of the combination of Bosutinib and Exemestane was acceptable 25% of subjects had treatment related liver events including 14% of severe liver events.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Woman aged 18 years or older.
- •Confirmed pathologic diagnosis of breast cancer.
- •Locally advanced, metastatic, or locoregional recurrent breast cancer not amenable to curative treatment with surgery or radiotherapy.
- •Surgically sterile or postmenopausal woman.
- •Documented ER+ and/or PgR+ and erbB2- tumor.
- •Progression of locally advanced or metastatic disease during treatment with a nonsteroidal AI or tamoxifen, or progression during treatment with (or within 6 months of discontinuation of) an adjuvant nonsteroidal AI.
排除标准
- •Prior exemestane, prior bosutinib, or any other prior anti-Src therapy.
- •More than 1 prior endocrine treatment for locally advanced or MBC.
- •More than 1 prior cytotoxic chemotherapy regimen in metastatic setting.
- •Bone or skin as the only site of disease.
研究组 & 干预措施
1
combination of bosutinib and exemestane
干预措施: Bosutinib (Drug)
1
combination of bosutinib and exemestane
干预措施: Exemestane (Drug)
2
exemestane
干预措施: Exemestane (Drug)
结局指标
主要结局
Progression Free Survival (PFS) Based on Independent Radiologist
时间窗: Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose
Time in weeks from randomization to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of randomization plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\]), or from adverse event (AE) data (where the outcome was "Death").
次要结局
- Percentage of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs)(Baseline up to 28 days after the last dose)
- Progression Free Survival (PFS) Based on Investigator(Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose)
- Percentage of Participants With Objective Response(Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose)
- Overall Survival (OS)(Part 2 Baseline until death or up to 24 months)
- Duration of Response (DR)(Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose)
- Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B)(Part 2 Baseline, Week 12, 2 to 6 weeks after last dose)
- Euro Quality of Life (EQ-5D)- Health State Profile Utility Score(Part 2 Baseline, Week 12, 2 to 6 weeks after last dose)
- Euro Quality of Life (EQ-5D)- Visual Analog Scale (VAS)(Part 2 Baseline, Week 12, 2 to 6 weeks after last dose)
- Maximum Observed Plasma Concentration (Cmax)(0 hour (pre-dose) on Day 1, 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 29)
- Time to Reach Maximum Observed Plasma Concentration (Tmax)(0 hour (pre-dose) on Day 1, 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 29)
- Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)](0 hour (pre-dose) on Day 1, 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 29)