A Randomized, Phase II, Placebo-controlled Study of Ipatasertib (GDC-0068), an Inhibitor to Akt, in Combination With Fluoropyrimidine Plus Oxaliplatin in Patients With Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 153
- 试验地点
- 34
- 主要终点
- Progression-Free Survival (PFS) in All Randomized Participants and Participants With PTEN Loss Tumors at Primary Analysis
研究概览
简要总结
This multicenter, randomized, double-blind, placebo-controlled study will evaluate the efficacy of ipatasertib in combination with oxaliplatin, 5-fluorouracil, and leucovorin (modified FOLFOX6 [mFOLFOX6]) chemotherapy in participants with advanced or metastatic gastric or gastroesophageal junction (GEJ) cancer. Participants will be randomized to receive either ipatasertib or placebo orally daily on Days 1 to 7 of each 14-day cycle in combination with mFOLFOX6 on Day 1 of each cycle.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Histologically documented, inoperable locally advanced or metastatic or recurrent gastric/GEJ adenocarcinoma, not amenable to curative therapy
- •Measurable disease, according to RECIST v1.1
- •Life expectancy greater than or equal to (>/=) 12 weeks
- •Adequate hematologic and organ function
排除标准
- •Previous chemotherapy for inoperable locally advanced or metastatic gastric/GEJ adenocarcinoma. Participants may have received prior neoadjuvant or adjuvant chemotherapy and/or radiation treatment for locally advanced gastric/GEJ adenocarcinoma, provided all treatments were completed >/= 6 months prior to randomization.
- •Known human epidermal growth factor receptor 2 (HER2)-positive gastric/GEJ adenocarcinoma
- •Radiation treatment within 28 days of randomization. Participants who have received palliative radiation treatment to peripheral sites (eg, bone metastases) within 28 days of randomization may be enrolled in the study if they have recovered from all acute, reversible effects and with notification of the Medical Monitor.
- •Previous therapy for gastric/GEJ adenocarcinoma with Akt, phosphatidylinositol 3-kinase (PI3K), and/or mammalian target of rapamycin (mTOR) inhibitors
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization or anticipation of need for a major surgical procedure during the course of the study
研究组 & 干预措施
Ipatasertib + mFOLFOX6
Participants will receive oral ipatasertib on Days 1 to 7 of each 14-day cycle in combination with mFOLFOX6, administered on Day 1 of each cycle.
干预措施: 5-Fluorouracil (Drug)
Ipatasertib + mFOLFOX6
Participants will receive oral ipatasertib on Days 1 to 7 of each 14-day cycle in combination with mFOLFOX6, administered on Day 1 of each cycle.
干预措施: Ipatasertib (Drug)
Ipatasertib + mFOLFOX6
Participants will receive oral ipatasertib on Days 1 to 7 of each 14-day cycle in combination with mFOLFOX6, administered on Day 1 of each cycle.
干预措施: Leucovorin (Drug)
Ipatasertib + mFOLFOX6
Participants will receive oral ipatasertib on Days 1 to 7 of each 14-day cycle in combination with mFOLFOX6, administered on Day 1 of each cycle.
干预措施: Oxaliplatin (Drug)
Placebo + mFOLFOX6
Participants will receive the placebo equivalent to ipatasertib on Days 1 to 7 of each 14-day cycle in combination with mFOLFOX6, administered on Day 1 of each cycle.
干预措施: 5-Fluorouracil (Drug)
Placebo + mFOLFOX6
Participants will receive the placebo equivalent to ipatasertib on Days 1 to 7 of each 14-day cycle in combination with mFOLFOX6, administered on Day 1 of each cycle.
干预措施: Leucovorin (Drug)
Placebo + mFOLFOX6
Participants will receive the placebo equivalent to ipatasertib on Days 1 to 7 of each 14-day cycle in combination with mFOLFOX6, administered on Day 1 of each cycle.
干预措施: Oxaliplatin (Drug)
Placebo + mFOLFOX6
Participants will receive the placebo equivalent to ipatasertib on Days 1 to 7 of each 14-day cycle in combination with mFOLFOX6, administered on Day 1 of each cycle.
干预措施: Placebo (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) in All Randomized Participants and Participants With PTEN Loss Tumors at Primary Analysis
时间窗: Screening, at the end of Cycle 4 (cycle = 14 days) and every fourth cycle thereafter until disease progression or death, whichever occurred first, assessed up to approximately 1.75 years
PFS was defined as the time from randomization to the first occurrence of disease progression (as determined using RECIST Version 1.1 and assessed by the investigator), or death from any cause on study. Progressive disease (PD): At least a 20% increase in the sum of diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 mm or progression of non-target lesions. Death on study was defined as death from any cause within 30 days of the last dose of study treatment regimen. Kaplan-Meier estimates were used for evaluation.
次要结局
- Overall Survival (OS)(Baseline up to end of study (up to approximately 7.5 years))
- Objective Response Rate (ORR)(Screening, at the end of Cycle 4 (cycle = 14 days) and every fourth cycle thereafter until disease progression or death, whichever occurred first, up to end of study (up to approximately 7.5 years))
- Duration of Objective Tumor Response(Screening, at the end of Cycle 4 (cycle = 14 days) and every fourth cycle thereafter until disease progression or death, whichever occurred first, up to end of study (up to approximately 7.5 years))
- Number of Participants With Adverse Events (AEs)(Baseline until end of study (up to approximately 7.5 years))
- Serum Concentration of Ipatasertib(Day 1 at 1 hour and 4 hours post-dose; Day 5, pre-dose and 2 hours post-dose)