MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE 3 TRIAL OF FULVESTRANT (FASLODEX (REGISTERED)). WITH OR WITHOUT PD-0332991 (PALBOCICLIB) +/- GOSERELIN IN WOMEN WITH HORMONE RECEPTOR-POSITIVE, HER2-NEGATIVE METASTATIC BREAST CANCER WHOSE DISEASE PROGRESSED AFTER PRIOR ENDOCRINE THERAPY
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 521
- 试验地点
- 217
- 主要终点
- Progression-Free Survival (PFS) as Assessed by the Investigator
研究概览
简要总结
The study is a randomized, double blind, placebo controlled, Phase 3 clinical trial with the primary objective of demonstrating the superiority of palbociclib in combination with fulvestrant (Faslodex®) over fulvestrant alone in prolonging PFS in women with HR+, HER2 negative metastatic breast cancer whose disease has progressed after prior endocrine therapy. The safety between the two treatment arms will also be compared. During study treatment, pre- and perimenopausal women must be receiving therapy with the LHRH agonist goserelin (Zoladex® or generic).
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
- Triple (Participant, Care Provider, Investigator)
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
- •Women 18 years or older with metastatic or locally advanced disease, not amenable to curative therapy
- •Confirmed diagnosis of HR+/HER2- breast cancer
- •Any menopausal status
- •Progressed within 12 months from prior adjuvant or progressed within 1 month from prior advanced/metastatic endocrine breast cancer therapy
- •On an LHRH agonist for at least 28 days, if pre-/peri-menopausal, and willing to switch to goserelin (Zoladex ®) at time of randomization.
- •Measurable disease defined by RECIST version 1.1, or bone-only disease
- •Eastern Cooperative Oncology Group (ECOG) PS 0-1
- •Adequate organ and marrow function, resolution of all toxic effects of prior therapy or surgical procedures
- •Patient must agree to provide tumor tissue from metastatic tissue at baseline
排除标准
- •Prior treatment with any CDK inhibitor, fulvestrant, everolimus, or agent that inhibits the PI3K-mTOR pathway
- •Patients with extensive advanced/metastatic, symptomatic visceral disease, or known uncontrolled or symptomatic CNS metastases
- •Major surgery or any anti-cancer therapy within 2 weeks of randomization
- •Prior stem cell or bone marrow transplantation
- •Use of potent CYP3A4 inhibitors or inducers
研究组 & 干预措施
Arm A
Given until objective progression, symptomatic deterioration, unacceptable toxicity, death, or withdrawal of consent, whichever occurs first.
干预措施: Palbociclib (Drug)
Arm A
Given until objective progression, symptomatic deterioration, unacceptable toxicity, death, or withdrawal of consent, whichever occurs first.
干预措施: Fulvestrant (Drug)
Arm B
Given until objective progression, symptomatic deterioration, unacceptable toxicity, death, or withdrawal of consent, whichever occurs first.
干预措施: Placebo (Drug)
Arm B
Given until objective progression, symptomatic deterioration, unacceptable toxicity, death, or withdrawal of consent, whichever occurs first.
干预措施: Fulvestrant (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 (assessed up to 12 months)
PFS is 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 absence of documented PD. Participants lacking an evaluation of tumor response after randomization had their PFS time censored on the date of randomization with the duration of a day. Participants with documentation of PD or death after a long interval (2 or more incomplete or non-evaluable assessments) since the last tumor assessment were censored at the time of last objective assessment that did not show PD. The length of PFS was calculated as PFS time (months) =\[progression/death date(censor date) - randomization date + 1\]/30.4. Progression is defined using Response Evaluation Criteria in Solid Tumors(RECIST v1.1) a 20% increase in the sum of diameters of target lesions and the sum must also demonstrate an absolute increase of at least 5mm or unequivocal progression of existing non-target lesions or the appearance of new lesions.
次要结局
- Ctrough for Goserelin(Cycles 2/ Day 1 and Cycle 3/ Day 1)
- Overall Survival (OS)-Number of Participants Who Died(From randomization until death (up to 4.5 years))
- Overall Survival (OS)(From randomization until death (up to 4.5 years))
- Survival Probabilities at Year 1, Year 2, and Year 3(From randomization until death (assessed up to 36 months))
- Objective Response (OR)(From randomization until end of treatment (assessed up to 2 years))
- Duration of Response (DR)(From randomization until end of treatment (assessed up to 2 years))
- Clinical Benefit Response (CBR)(From randomization until end of treatment (assessed up to 2 years))
- Observed Plasma Trough Concentration (Ctrough) for Palbociclib(Cycle 1/Day 15 and Cycle 2/Day 15)
- Ctrough for Fulvestrant(Cycles 2/Day 1 and Cycle 3/Day 1)
- Change From Baseline Between Treatment Comparison in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Functional Scale Scores(From Cycle 1 to 14, as of 05 December 2014.)
- Change From Baseline Between Treatment Comparison in EORTC QLQ-C30 Symptom Scale Scores(From Cycle 1 to 14, as of 05 December 2014.)
- Change From Baseline Between Treatment Comparison in European Organization for Research and Treatment of Cancer Breast Cancer Module (EORTC QLQ BR23) Functional Scale Scores(From Cycle 1 to 14, as of 05 December 2014.)
- Change From Baseline Between Treatment Comparison in EORTC QLQ BR23 Symptom Scale Scores(From Cycle 1 to 14, as of 05 December 2014.)
- Change From Baseline Between Treatment Comparison in EuroQoL 5D (EQ-5D)- Health Index Scores(From Cycle 1 to 14, as of 05 December 2014.)
- Change From Baseline Between Treatment Comparison in EQ-5D Visual Analog Scale (VAS) Scores Scale(From Cycle 1 to 14, as of 05 December 2014.)
- Time to Deterioration (TTD)(Baseline, Day 1 of Cycles 2 to 4, Day 1 of every alternate cycle after that until the end of treatment, as of 05 December 2014)
- Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs; All Causalities)(From the date of randomization up to 28 calendar days (±7 days) after last dose of study intervention (up to 8.4 years).)
- Participants With Shifts From CTCAE Grade ≤2 at Baseline to CTCAE Grade 3 or 4 Postbaseline for Hematology Results(From baseline to end of treatment/withdrawal (up to 4.5 years))
- Participants With Shifts From CTCAE Grade ≤2 at Baseline to CTCAE Grade 3 or 4 Postbaseline for Chemistry Results(From baseline to end of treatment/withdrawal (up to 4.5 years))