A Phase 2 Randomized Open-Label Study Of Letrozole In Combination With Two Dose Levels And Schedules Of Oral Temsirolimus (CCI-779), Or Letrozole Alone, In Postmenopausal Women With Locally Advanced Or Metastatic Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 108
- 主要终点
- Percentage of Participants With Objective Response (OR)
研究概览
简要总结
To evaluate the preliminary activity and pharmacokinetics of 2 separate doses and schedules of orally administered Temsirolimus (CCI-779) given in combination with daily letrozole, compared to letrozole alone, in the treatment of locally advanced or metastatic breast cancer in postmenopausal women. All patients must be appropriate to receive endocrine therapy as treatment for advanced disease.
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
- •Postmenopausal women with histologically confirmed, measurable locally advanced disease or metastatic breast.
- •Must be appropriate to receive endocrine therapy as treatment for advanced disease (chemotherapy; prior adjuvant therapy with antiestrogens other than aromatase inhibitors; prior adjuvant or first-line metastatic therapy with tamoxifen or trastuzumab, are permitted).
- •Women may either present with de novo advanced or metastatic cancer, or have had tumor progression while receiving adjuvant tamoxifen or at any time after completing adjuvant tamoxifen, or have had tumor progression while receiving first-line metastatic therapy with tamoxifen.
排除标准
- •Patients having known central nervous system (CNS) metastases.
- •Prior therapy with Temsirolimus (CCI-779) or aromatase inhibitors.
- •Tamoxifen, or other hormonal therapy, in the metastatic or adjuvant setting within 1 week prior to day 1 of treatment on study.
研究组 & 干预措施
A
干预措施: Letrozole / Temsirolimus (CCI-779) (Drug)
B
干预措施: Letrozole / Temsirolimus (CCI-779) (Drug)
C
干预措施: Letrozole (Drug)
结局指标
主要结局
Percentage of Participants With Objective Response (OR)
时间窗: Baseline, every 4 cycles (1 cycle is defined as a 14 day duration) up to Cycle 25, then every 6 cycles until disease progression
OR measured as Complete response (CR) or Partial response (PR) confirmed by assessments performed no less than 4 weeks after the criteria for the response are first met. CR=disappearance of all target and non-target lesions with normalization of tumor marker level; PR=at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, referencing the screening sum LD. Target lesions=all measurable lesions up to 5 lesions per organ (10 lesions in total), representative of all involved organs, if possible; recorded and measured at screening. Non-target lesions=all other lesions.
次要结局
- Percentage of Participants With Best Overall Response (Clinical Benefit)(Baseline, every 4 cycles (1 cycle is defined as a 14 day duration) up to Cycle 25, then every 6 cycles until disease progression))
- Time to Disease Progression(Baseline, every 4 cycles (1 cycle is defined as a 14 day duration) up to Cycle 25, then every 6 cycles until disease progression))
- Time to Treatment Failure(Baseline until Progressive disease, death, or discontinuation of study treatment)
- Percentage of Participants Exhibiting Freedom From Progression(Baseline, 8 weeks, 6 months, 12 months, and 24 months)
- Duration of Response(Baseline, every 4 cycles (1 cycle is defined as a 14 day duration) up to Cycle 25, then every 6 cycles until disease progression))
- Number of Participants With Survival(Baseline, every 4 cycles (1 cycle is defined as a 14 day duration) until death)
- Health Outcomes Assessment: EuroQol (EQ-5D) Health State Profile Score(Prior to baseline, Cycle 7 (Week 12) and final visit (within 15 days of stopping study treatment))
- Health Outcomes Assessment: European Organization for Research and Treatment of Cancer Quality of Life Questionaire (EORTC QLQ) BR23(Prior to baseline, Cycle 7 (Week 12) and final visit (within 15 days of stopping study treatment))
- Number of Participants With Antitumor Response in Relation to Expression of Akt Phosphorylation, Cyclin D1, PTEN, and p27(Prior to baseline, after Cycle 4 (Week 8), after Cycle 8 (Week 14), and cross-over or final visit (within 15 days of stopping study treatment))
- Area Under the Concentration-time Curve (AUC) Sum(Cycle 1 Day 1 (1 cycle is defined as a 14 day duration) , Cycle 3 Day 1, and Cycle 4 Day 1, Day 6, Day 9, Day 11, and Day 12)
- 24-hour Trough Concentration (C Trough)(Cycle 1 Day 1 (1 cycle is defined as a 14 day duration) , Cycle 3 Day 1, and Cycle 4 Day 1, Day 6, Day 9, Day 11, and Day 12)