A Randomized, Phase II, Multi-Center, Placebo-Controlled Study of Ipatasertib (GDC-0068), an Inhibitor of Akt, in Combination With Paclitaxel as Front-Line Treatment for Patients With Metastatic Triple-Negative Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 124
- 试验地点
- 43
- 主要终点
- PFS in Participants With Phosphatase and Tensin Homolog (PTEN)-Low Tumors
研究概览
简要总结
This multicenter, randomized, double-blind study will estimate the efficacy, safety and tolerability of ipatasertib combined with paclitaxel compared with placebo combined with paclitaxel in participants with inoperable locally advanced or metastatic triple-negative breast cancer (mTNBC), as measured by progression-free survival (PFS) in all participants and in participants with phosphatase and tensin homolog (PTEN)-low tumors.
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
- Double (Participant, 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
- •Histologically documented triple-negative adenocarcinoma of the breast that is inoperable locally advanced or metastatic and is not amenable to resection with curative intent
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen, required prior to randomization
- •Measurable disease, according to the RECIST v1.1
- •Adequate hematologic and organ function within 14 days before the first study treatment
- •For female participants of childbearing potential, agreement (by both participant and partner) to use an effective form of contraception for the duration of the study and for 6 months after last dose of study treatment
排除标准
- •Any previous therapy, including chemotherapy or hormonal or targeted therapy, for inoperable locally advanced or metastatic triple-negative adenocarcinoma of the breast. Participants may have received prior neoadjuvant or adjuvant chemotherapy and/or radiation treatment for locally advanced triple negative adenocarcinoma, provided all treatments were completed greater than or equal to (>/=) 6 months prior to Cycle 1 Day
- •Locally recurrent disease must not be amenable to resection with curative intent
- •Any radiation treatment to metastatic site within 28 days of Cycle 1, Day 1
- •Known Human Epidermal Growth Factor Receptor 2 (HER2) positive, erythrocyte receptor (ER) positive, or progesterone receptor (PR) positive breast cancer
- •Previous therapy with Akt, PI3K, and/or mTOR inhibitors
- •Major surgical procedure, open biopsy, or significant traumatic injury within 30 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study
- •Known presence of the brain or spinal cord metastasis, as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening or prior radiographic assessments
研究组 & 干预措施
Ipatasertib + Paclitaxel
Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
干预措施: Ipatasertib (Drug)
Ipatasertib + Paclitaxel
Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
干预措施: Paclitaxel (Drug)
Placebo + Paclitaxel
Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with placebo matching ipatasertib, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
干预措施: Paclitaxel (Drug)
Placebo + Paclitaxel
Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with placebo matching ipatasertib, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
干预措施: Placebo (Drug)
结局指标
主要结局
PFS in Participants With Phosphatase and Tensin Homolog (PTEN)-Low Tumors
时间窗: Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 07 June 2016)
PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1 or death on study (\<=30 days after the last dose of study treatment regimen) from any cause, whichever occurred first.
Progression Free Survival (PFS)
时间窗: Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 07 June 2016)
PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1 or death on study (\<=30 days after the last dose of study treatment regimen) from any cause, whichever occurred first.
次要结局
- PFS in Participants With Phosphatidylinositol-4,5-bisphosphate 3-kinase Catalytic Subunit Alpha (PIK3CA)/ Protein Kinase B (AKT1)/ PTEN-altered Tumors(Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 07 June 2016))
- Overall Survival (OS)(Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 31 August 2019))
- Duration of Response in Participants With PIK3CA/AKT1/PTEN-altered Tumors(Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016))
- OS in Participants With PIK3CA/AKT1/PTEN-altered Tumors(Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 31 August 2019))
- Duration of Response(Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016))
- Time to Disease Progression(Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016))
- OS in Participants With PTEN-Low Tumors(Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 31 August 2019))
- ORR in Participants With PIK3CA/AKT1/PTEN-altered Tumors(Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016))
- ORR in Participants With PTEN-Low Tumors(Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016))
- Patient Reported Outcome (PRO) Measure: Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) Score(Baseline (Cycle 1 Day 1) up to Cycle 5 Day 1)
- Duration of Response in Participants With PTEN-Low Tumors(Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016))
- Pharmacokinetic Endpoint: Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 24 Hours (AUC0-24h) of Ipatasertib(Cycle 1 Day 1, Cycle 1 Day 8)
- PRO Measure: Percentage of Participants With Improved, Worsened, or Remained Stable for Bothersome Side Effects of Treatment Measured by the Scales of the EORTC QLQ-C30(Baseline (Cycle 1 Day 1) up to Cycle 5 Day 1)
- Objective Response Rate (ORR)(Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016))
- Time to Disease Progression in Participants With PTEN-Low Tumors(Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016))
- Time to Disease Progression in Participants With PIK3CA/AKT1/PTEN-altered Tumors(Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016))
- Safety: Percentage of Participants With Adverse Events(Baseline up to 30 days after the last dose of study drug or until initiation of another anti-cancer therapy, whichever occurs first (up to 3 years, 3 months))
- Pharmacokinetic Endpoint: Apparent Clearance Following Oral Dosing (CL/F) of Ipatasertib(Cycle 1 Day 1, Cycle 1 Day 8)