A RANDOMIZED, MULTICENTER, DOUBLE-BLIND PHASE 3 STUDY OF PD-0332991 (ORAL CDK 4/6 INHIBITOR) PLUS LETROZOLE VERSUS PLACEBO PLUS LETROZOLE FOR THE TREATMENT OF POSTMENOPAUSAL WOMEN WITH ER (+), HER2 (-) BREAST CANCER WHO HAVE NOT RECEIVED ANY PRIOR SYSTEMIC ANTI CANCER TREATMENT FOR ADVANCED DISEASE
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 666
- 试验地点
- 273
- 主要终点
- Progression-Free Survival (PFS) as Assessed by the Investigator
研究概览
简要总结
The study is designed to compare the clinical benefit following treatment with letrozole in combination with PD-0332991 versus letrozole in combination with placebo in 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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Adult 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] 0-2
- •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 (neo)adjuvant treatment with letrozole or anastrozole with DFI ≤ 12-months from completion of treatment.
- •Prior treatment with any CDK 4/6 inhibitor.
研究组 & 干预措施
PD-0332991 + Letrozole
PD-0332991, 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: PD-0332991 (Drug)
PD-0332991 + Letrozole
PD-0332991, 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: Placebo (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) as Assessed by the Investigator
时间窗: From randomization date to date of first documentation of progression or death (up to approximately 2.5 years)
PFS is defined as the time from the date of randomization to the date of the first documentation of objective tumor progression as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) or death due to any cause in the absence of documented PD, whichever occurs first. If tumor progression data include more than 1 date, the first date will be used. PFS (in months) will be calculated as (first event date - randomization date +1)/30.4. Progression is defined using RECIST v1.1, as a 20% increase in the sum 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, or unequivocal progression of pre-existing non-target lesions, or the appearance of new lesions.
次要结局
- Objective Response as Assessed by the Investigator(From randomization until end of treatment (up to approximately 2.5 years))
- Objective Response: Participants With Measurable Disease at Baseline as Assessed by the Investigator(From randomization until end of treatment (up to approximately 2.5 years))
- Duration of Response (DR)(From randomization until end of treatment (up to approximately 2.5 years))
- Disease Control (DC)/Clinical Benefit Response (CBR)(From randomization until end of treatment (up to approximately 2.5 years))
- PFS by Tumor Tissue Biomarkers Status, Including Genes (eg, Copy Numbers of CCND1, CDKN2A), Proteins (eg, Ki67, pRb), and RNA Expression (eg, cdk4, cdk6)(From randomization until end of treatment (up to approximately 24 Months))
- Corrected QT Interval (QTc) Time-Matched Change From Baseline on Cycle 1 Day 14(Time-matched triplicate ECGs were collected at 0 (predose), 2, 4, 6 and 8 hours on Day 0 and on Cycle1 Day14)
- Observed Plasma Trough Concentration (Ctrough) at Steady-State(0 hour (predose) on Day 14 of cycles 1 and 2)
- Percentage of Participants With Corrected QT Interval (QTc)(For safety monitoring triplicate ECGs were obtained at 0 hour (pre-dose) on Day 1 of Cycle 1, Day 14 of Cycles 1 and Cycle 2, then on Day 1 of Cycles 4, 7, and 10 (ECGs beyond Cycle 10 were performed as clinically indicated))
- Change From Baseline Between Treatment Comparison in Euro Quality of Life (EQ-5D) Index(From Baseline up to 2.5 years)
- Change From Baseline Between Treatment Comparison in Functional Assessment of Cancer Therapy-Breast (FACT-B)(From Baseline up to 2.5 years)
- Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs): All Causalities(From date of randomization up to 28 days after last dose of study drug (final analysis till study completion, approximately up to 10.51 years))
- Overall Survival (OS): Primary Analysis(From date of randomization until death due to any cause or censored, (assessed up to data cut-off date of 15-Nov-2021, approximately 8.7 years))
- Overall Survival (OS): Final Analysis(From date of randomization until death due to any cause or censored (final analysis till study completion, approximately up to 10.51 years))
- Survival Probability at 1 Year, 2 Year and 3 Year(1, 2 and 3 years after randomization)
- Number of Participants With Laboratory Abnormalities by Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade(From randomization up to 28 days after last dose of study drug (assessed up to analysis date of 15-Nov-2021, approximately 8.7 years))