A Phase Ib/III Study of Ipatasertib Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Hormone Receptor Positive and HER2 Negative Locally Advanced Unresectable or Metastatic Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 20
- 试验地点
- 20
- 主要终点
- Phase III: Progression-Free Survival (PFS), as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
研究概览
简要总结
The open-label Phase Ib portion of this study will evaluate the safety and pharmacokinetics of ipatasertib in combination with palbociclib and fulvestrant to identify a dose of ipatasertib that can be combined with palbociclib and fulvestrant in the Phase III portion. The randomized Phase III portion of this study will evaluate the efficacy, safety, and patient-reported outcome (PRO) objectives of ipatasertib + palbociclib + fulvestrant compared with placebo + palbociclib + fulvestrant in patients with HR+ HER2-, locally advanced unresectable or metastatic breast cancer who had relapsed during adjuvant endocrine therapy or progressed during the initial 12 months of first-line endocrine therapy in locally advanced unresectable or metastatic breast cancer.
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
- All
- 接受健康志愿者
- 否
入选标准
- •HR+ HER2- adenocarcinoma of the breast that is locally advanced unresectable or metastatic
- •For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs
- •For men: agreement to remain abstinent or use contraceptive methods, and agreement to refrain from donating sperm
- •Radiologic/objective relapse during adjuvant endocrine therapy or disease progression during the initial 12 months of 1L endocrine therapy in locally advanced unresectable or metastatic breast cancer
- •At least one measurable lesion via Response Evaluation Criteria in Solid Tumors, Version 1.1
- •Phase III only: Tumor specimen from the most recently collected, available tumor tissue
排除标准
- •Pregnant or breastfeeding, or intending to become pregnant
- •Prior treatment with fulvestrant or other selective estrogen receptor down-regulator
- •Prior treatment with PI3K inhibitor, mTOR inhibitor or AKT inhibitor
- •Phase III only: Prior treatment with CDK4/6 inhibitor for locally advanced unresectable or metastatic breast cancer
- •Prior treatment with a cytotoxic chemotherapy regimen for metastatic breast cancer
- •History of Type I or Type II diabetes mellitus requiring insulin
- •History of or active inflammatory bowel disease or active bowel inflammation
- •Lung disease: pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, Aspergillosis, active tuberculosis, or history of opportunistic infections
研究组 & 干预措施
Phase 1b and Phase 3: Ipatasertib + Palbociclib +Fulvestrant
干预措施: Ipatasertib (Drug)
Phase 1b and Phase 3: Ipatasertib + Palbociclib +Fulvestrant
干预措施: Palbociclib (Drug)
Phase 1b and Phase 3: Ipatasertib + Palbociclib +Fulvestrant
干预措施: Fulvestrant (Drug)
Phase 3: Placebo + Palbociclib + Fulvestrant
干预措施: Placebo (Drug)
Phase 3: Placebo + Palbociclib + Fulvestrant
干预措施: Palbociclib (Drug)
Phase 3: Placebo + Palbociclib + Fulvestrant
干预措施: Fulvestrant (Drug)
结局指标
主要结局
Phase III: Progression-Free Survival (PFS), as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
时间窗: From randomization in Phase III until the first occurrence of disease progression or death from any cause, whichever occurs first, up to approximately 36 months
PFS was defined as the time from randomization to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. Progressive disease (PD) is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of ≥ 5 millimeters (mm).
次要结局
- Phase Ib: Number of Participants With Adverse Events and Adverse Events With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)(Up to 36 Months)
- Phase Ib: Plasma Concentration of Ipatasertib and Its Metabolite G-037720(Cycle 1, Day 1 and 15: 0.25 hours pre-dose, 0.5, 1, 2, 3, 4 and 6 hours post- dose ; Cycle 2, Day 15: 0.25 hours pre-dose; Cycle 3, Day 15: 0.15 hours pre-dose, 2 hours post-dose (each cycle = 28 days))
- Phase Ib: Maximum Concentration (Cmax) of Ipatasertib and Its Metabolite G-037720 in Plasma(Cycle 1: Day 1 and Day 15)
- Phase Ib: Area Under the Plasma Concentration Time-curve From Zero to 24 Hours (AUC0-24) of Ipatasertib and Its Metabolite G-037720(Cycle 1: Day 1 and Day 15)
- Phase Ib: Time to Maximum Concentration (Tmax) of Ipatasertib and Its Metabolite G-037720(Cycle 1: Day 1 and Day 15)
- Phase III: Objective Response Rate (ORR) as Determined by the Investigator According to RECIST v1.1(From randomization in Phase III up to approximately 36 months)
- Phase III: Duration of Objective Response (DOR) as Determined by the Investigator According to RECIST v1.1(From randomization in Phase III until the first occurrence of disease progression or death from any cause, whichever occurs first, up to approximately 36 months)
- Phase III: Clinical Benefit Rate (CBR) as Determined by the Investigator According to RECIST v1.1(From randomization in Phase III until the first occurrence of disease progression or death from any cause, whichever occurs first, up to approximately 36 months)
- Phase III: Overall Survival (OS) as Determined by the Investigator According to RECIST v1.1(From randomization in Phase III until the first occurrence of disease progression or death from any cause, whichever occurs first, up to approximately 36 months)
- Phase III: Time to Deterioration (TTD) in Severity of Pain, According to the Brief Pain Inventory-Short Form (BPI-SF)(From randomization in Phase III to the first documentation of a ≥2-point increase in pain scale (up to approximately 36 months))
- Phase III: TTD in Presence and Interference of Pain According to the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Pain Scale(From randomization in Phase III to the first documentation of a ≥10-point increase (up to approximately 36 months))
- Phase III: TTD in Physical Functioning (PF), Role Functioning (RF), GHS/QoL According to EORTC QLQ-C30(From randomization in Phase III to the first documentation of a ≥10-point decrease in the PF, RF and GHS/QoL of EORTC QLQ-C30 (up to approximately 36 months))
- Phase III: Number of Participants With Adverse Events(Up to approximately 36 months)