A MULTICENTER, RANDOMIZED, DOUBLE-BLIND PHASE 3 STUDY OF PALBOCICLIB (ORAL CDK 4/6 INHIBITOR) PLUS LETROZOLE VERSUS PLACEBO PLUS LETROZOLE FOR THE TREATMENT OF PREVIOUSLY UNTREATED ASIAN POSTMENOPAUSAL WOMEN WITH ER (+), HER2 (-) ADVANCED BREAST CANCER
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 340
- 试验地点
- 103
- 主要终点
- Progression-Free Survival (PFS) Based on Investigator's Assessment
研究概览
简要总结
The study is designed to compare the clinical benefit following treatment with letrozole in combination with Palbociclib versus letrozole in combination with placebo in Asian postmenopausal women with ER(+)/HER2(-) advanced breast cancer who have not received prior systemic anti cancer therapies for their advanced/metastatic 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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Adult Asian women with locoregionally recurrent or metastatic disease not amenable to curative therapy
- •Confirmed diagnosis of ER positive breast cancer
- •No prior systemic anti-cancer therapy for advanced ER+ disease
- •Postmenopausal women
- •Measurable disease as per Response Evaluation Criterion in Solid Tumors [RECIST] or bone-only disease
- •Eastern Cooperative Oncology Group [ECOG] 0-1
- •Adequate organ and marrow function
- •Patient must agree to provide tumor tissue
排除标准
- •Confirmed diagnosis of HER2 positive disease
- •Patients with advanced, symptomatic, visceral spread that are at risk of life threatening complication in the short term
- •Known uncontrolled or symptomatic CNS metastases
- •Prior neoadjuvant or adjuvant treatment with a non steroidal aromatase inhibitor (ie, anastrozole or letrozole) with disease recurrence while on or within 12 months of completing treatment
- •Prior treatment with any CDK 4/6 inhibitor
研究组 & 干预措施
Placebo + Letrozole
Placebo, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment in combination with Letrozole, 2.5mg, orally once daily (continuously).
干预措施: Placebo (Drug)
Palbociclib + Letrozole
Palbociclib, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment in combination with Letrozole, 2.5mg, orally once daily (continuously)
干预措施: Palbociclib (Drug)
Palbociclib + Letrozole
Palbociclib, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment in combination with Letrozole, 2.5mg, orally once daily (continuously)
干预措施: Letrozole (Drug)
Placebo + Letrozole
Placebo, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment in combination with Letrozole, 2.5mg, orally once daily (continuously).
干预措施: Letrozole (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) Based on Investigator's Assessment
时间窗: Randomization up to 65 months
PFS was based on Kaplan-Meier estimates. PFS was defined as the time from the date of randomization to the date of the first documentation of objective progression of disease (PD) or death due to any cause in the absence of documented PD, whichever occurred first. PD is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as a 20% increase in the sum of of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm. In this outcome measure, PFS was based on investigator's assessment.
次要结局
- Percentage of Participants With Objective Response (OR) Based on Blinded Independent Central Review (BICR) (Participants With Measureable Disease at Baseline)(Randomization up to 65 months)
- Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR)(Randomization up to 65 months)
- Percentage of Participants With Objective Response (OR) Based on Investigator Assessment (Participants With Measureable Disease at Baseline)(Randomization up to 65 months)
- Percentage of Participants With Disease Control/Clinical Benefit Response (DC/CBR) Based on Investigator Assessment (Participants With Measureable Disease at Baseline)(Randomization up to 65 months)
- Percentage of Participants With Disease Control/Clinical Benefit Response (DC/CBR) Based on Blinded Independent Central Review (BICR) (Participants With Measureable Disease at Baseline)(Randomization up to 65 months)
- Overall Survival (OS)(Randomization up to 65 months)
- Number of Participants With Treatment-Emergent Adverse Events (Treatment Related)(Randomization up to 65 months)
- Trough Plasma Concentration of Palbociclib(Pre-dose on Day 14 of Cycle 1 and Cycle 2)
- Percentage of Participants Wiht Objective Response (OR) Based on Investigator Assessment(Randomization up to 65 months)
- Duration of Response (DOR) Based on Blinded Independent Central Review (BICR) (Participants With Objective Disease Response)(Randomization up to 65 months)
- Percentage of Participants With Disease Control/Clinical Benefit Response (DC/CBR) Based on Blinded Independent Central Review (BICR)(Randomization up to 65 months)
- Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events(CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Chemistry(Randomization up to 65 months)
- Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score(Baseline up to Cycle 65 Day 1)
- Percentage of Participants With Objective Response (OR) Based on Blinded Independent Central Review (BICR)(Randomization up to 65 months)
- Duration of Response (DOR) Based on Investigator Assessment (Participants With Objective Disease Response)(Randomization up to 65 months)
- Percentage of Participants With Disease Control/Clinical Benefit Response (DC/CBR) Based on Investigator Assessment(Randomization up to 65 months)
- Number of Participants With Treatment-Emergent Adverse Events (All Causalities)(Randomization up to 65 months)
- Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Hematology(Randomization up to 65 months)
- Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores(Baseline up to Cycle 65 Day 1)
- 1-Year, 2-Year and 3-Year Survival Probability(Randomization up to 65 months)
- Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores(Baseline up to Cycle 65 Day 1)
- Median Baseline Percent (%) Positive Cells for Ki67(Baseline)
- Number of Participants With Detection in Estrogen Receptor (ER)(Baseline)