A PHASE 2, RANDOMIZED, OPEN-LABEL STUDY OF BOSUTINIB ADMINISTERED IN COMBINATION WITH LETROZOLE VS. LETROZOLE ALONE AS FIRST LINE THERAPY IN POST-MENOPAUSAL WOMEN WITH LOCALLY ADVANCED OR METASTATIC ER+/PR+/HER2- BREAST CANCER.
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 16
- 试验地点
- 11
- 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 study of bosutinib administered in combination with letrozole versus letrozole alone in post-menopausal women with breast cancer. This is a 2-part study. Subjects in part 1 will receive bosutinib and letrozole daily, and will be closely monitored for 28 days. The second part will proceed with subjects receiving a dose that is determined to be safe based on the safety evaluation of the first part. Eligible subjects will be randomly assigned to receive either bosutinib daily combined with daily letrozole, or daily letrozole alone for a specified period of time. Subjects will be followed up for survival after study drug discontinuation.
详细描述
This study was terminated on 19 April 2009 due to unfavorable risk benefit ratio of Bosutinib in combination with Letrozole including one confirmed Hy's law case. 37.5% of patients had treatment related liver events with the majority of severe events resulting in permanent study treatment discontinuation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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
- •Surgically sterile or post-menopausal women.
- •Confirmed pathologic diagnosis of breast cancer.
- •Locally advanced or metastatic, or loco-regional recurrent breast cancer not amenable to curative treatment with surgery or radiotherapy.
- •Documented ER+ and/or PgR+ and erbB2- tumor based on most recently analyzed biopsy, as documented by a local laboratory.
- •At least 1 radiologically measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST).
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
排除标准
- •Prior letrozole (except in adjuvant setting), prior bosutinib, or any other prior Src inhibitor.
- •Prior endocrine treatment for locally advanced or metastatic breast cancer (up to one prior adjuvant Aromatase Inhibitor (AI) agent/regimen is permitted).
- •More than 1 prior chemotherapy regimen in locally advanced or metastatic breast cancer.
- •Adjuvant endocrine therapy <=12 months prior to day 1 of treatment.
- •Disease refractory (ie, Progressive disease (PD) within 6 months from initiation of therapy) to previous adjuvant antiestrogen therapy.
- •Bone or skin as the only site of disease.
- •Extensive visceral disease or active Central Nervous System (CNS) disease.
- •Any other cancer within 5 years of screening with the exception of ER+ contralateral breast carcinoma, adequately treated cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the skin.
- •Major surgery or radiotherapy within 14 days of treatment day.
- •Inadequate hepatic/renal/bone marrow function.
- •History of clinically significant or uncontrolled cardiac disease.
- •Serious concurrent illness.
研究组 & 干预措施
1
Combination of Bosutinib and Letrozole
干预措施: Bosutinib (Drug)
1
Combination of Bosutinib and Letrozole
干预措施: Letrozole (Drug)
2
Letrozole
干预措施: Letrozole (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 date of randomization to first documentation of objective tumor progression or death due to any cause. PFS: calculated as (first event date minus the date of randomization plus 1) divided by 7. Tumor progression: 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"). PFS assessed by independent radiologist was to be reported.
次要结局
- Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B)(Part 2 Baseline, Week 12, 24, 52, 2-6 weeks 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 36 months)
- Duration of Response (DR)(Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose)
- Time to Reach Maximum Observed Plasma Concentration (Tmax)(0 hour (pre-dose) on Day 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; 2, 3, 4, 6, 8, 24 hours post-dose on Day 29)
- Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)(Part 1 Baseline up to 28 days after the last dose)
- Maximum Observed Plasma Concentration (Cmax)(0 hour (pre-dose) on Day 1; 2, 3, 4, 6, 8, 24 hours post-dose on Day 29)