A RANDOMIZED PHASE 2 NON-COMPARATIVE STUDY OF THE EFFICACY OF PF-04691502 AND PF-05212384 IN PATIENTS WITH RECURRENT ENDOMETRIAL CANCER
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 67
- 试验地点
- 47
- 主要终点
- Clinical Benefit Response for PF-04691502
研究概览
简要总结
This study will investigate the individual safety and efficacy of two dual PI3K/mTOR inhibitors in patients with recurrent endometrial cancer.
详细描述
The study was prematurely discontinued due to lack confidence in the Stathmin assay as a patient selection criteria and subsequent lack of confidence in the efficacy signal that was observed. The decision to terminate the study was made on January 23, 2014. It should be noted that safety concerns have not been seen in this study and have not factored into this decision.
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
- None
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
- •Recurrent endometrial carcinoma
- •Disease progression following one or two lines of prior treatment with platinum containing chemotherapy
- •Tumor tissue available at time of screening for PI3K analysis
- •Adequate performance status
- •Adequate glucose control, bone marrow, kidney, liver, and heart function
排除标准
- •More than 2 prior cytotoxic chemo regimens for endometrial carcinoma
- •Prior therapy with an agent known to be a PI3K, and or mTOR and or AKT inhibitor
- •Active brain metastases
研究组 & 干预措施
B
PI3K Basal, IV Compound
干预措施: PF-05212384 (Drug)
C
PI3K Activated, Oral Compound
干预措施: PF-05212384 (Drug)
F
Japanese lead in cohort, IV compound
干预措施: PF-05212384 (Drug)
结局指标
主要结局
Clinical Benefit Response for PF-04691502
时间窗: 16 weeks from Cycle 1 Day 1
Clinical benefit response was defined as best overall response of complete response (CR), partial response (PR) or stable disease (SD) for at least 16 weeks from Cycle 1 Day 1 (C1D1) to the first time of disease progression. The outcome data table below presents the number of participants with clinical benefit response as "yes" or "no". On 09 Oct 2012, Pfizer decided to stop enrollment into PF-04691502. While tumor assessment for PF-04691502 was included as a listing in the final report, formal efficacy analysis for PF-04691502 was not performed.
Percentage of Participants With Clinical Benefit Response for PF-05212384
时间窗: 16 weeks from Cycle 1 Day 1
Clinical benefit response was defined as best overall response of complete response (CR), partial response (PR) or stable disease (SD) for at least 16 weeks from Cycle 1 Day 1 (C1D1) to the first time of disease progression. The primary analysis is based on the clinical benefit rate which is calculated as proportion of participants with a clinical benefit response relative to total number of response evaluable participants. Per RECIST v1.1 for target lesions: CR defined as disappearance of all target lesions; PR defined as \>=30% decrease in the sum of the longest diameter of target lesions; SD does not qualify for CR, PR or Progression. All target lesions must be assessed. SD can follow PR only in the rare case that the sum increases by less than 20% from the nadir, but enough that a previously documented 30% decrease no longer holds. A Clopper-Pearson exact 95% CI for the clinical benefit rate is presented in the below table.
次要结局
- Objective Response for PF-04691502(Randomization to objective progression, death or last tumor assessment without progression (up to 12 months))
- Percentage of Participants With Progression Free Survival (PFS) at 6 Months for PF-05212384(6 months)
- Overall Survival (OS) for PF-05212384(12 months)
- Level of Each Pharmacodynamic Parameter at Specified Timepoints- Glucose (mg/dL)(Baseline (Day -3) and Cycle1 to Cycle 5 where each cycle consist of 28 days)
- Level of Each Pharmacodynamic Parameter at Specified Timepoints- Cholesterol (mg/dL)(Baseline (Day -3) and Cycle1 to Cycle 3 where each cycle consist of 28 days)
- Steady State Volume of Distribution (Vss) of PF-05212384 at Each Specified Time Points.(Pre-dose: 0 hours, and Post dose: 0.5 (after end of infusion), 1, 2, 4, 6, 24, 72, and 120 hours)
- Percentage of Participants With Objective Response for PF-05212384(Randomization to objective progression, death or last tumor assessment without progression (up to 12 months))
- Progression Free Survival for PF-04691502(From Cycle 1 Day 1 to objective progressive disease or death due to any cause whichever occurs first (up to 12 months))
- Progression Free Survival for PF-05212384(From Cycle 1 Day 1 to objective progressive disease or death due to any cause whichever occurs first (up to 12 months))
- Level of Each Pharmacodynamic Parameter at Specified Timepoints- Insulin (UIU/mL)(Baseline (Day -3) and Cycle1 to Cycle 5 where each cycle consist of 28 days)
- Level of Each Pharmacodynamic Parameter at Specified Timepoints- Glycosylated Hemoglobin (HbA1c)(Baseline (Day -3) and Cycle1 to Cycle 5 where each cycle consist of 28 days)
- Level of Each Pharmacodynamic Parameter at Specified Timepoints- Triglycerides (mg/dL)(Baseline (Day -3) and Cycle1 to Cycle 3 where each cycle consist of 28 days)
- Stathmin H Score [Mean (SD)] for Each Treatment Arm With Gene and/or Protein Expression Biomarkers in Biopsied Tumor Tissue(Prior to Cycle 1 Day 1)
- Area Under the Serum Concentration Time Profile From Time Zero Extrapolated to Infinity (AUCinf) of PF-05212384 at Each Specified Time Points.(Pre-dose: 0 hours, and Post dose: 0.5 (after end of infusion), 1, 2, 4, 6, 24, 72, and 120 hours at Day 1)
- Area Under the Serum Concentration Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-05212384 at Each Specified Time Points.(Pre-dose: 0 hours, and Post dose: 0.5 (after end of infusion), 1, 2, 4, 6, 24, 72, and 120 hours at Day 1)
- Maximum Plasma Concentration (Cmax) of PF-05212384 at Each Specified Time Points.(Pre-dose: 0 hours, and Post dose: 0.5 (after end of infusion), 1, 2, 4, 6, 24, 72, and 120 hours at Day 1)
- Terminal Elimination Half Life (t½) of PF-05212384 at Each Specified Time Points.(Pre-dose: 0 hours, and Post dose: 0.5 (after end of infusion), 1, 2, 4, 6, 24, 72, and 120 hours at Day 1)
- Percentage of Participants in Each Treatment Arm With Gene and/or Protein Expression Biomarkers- PIK3CA Amplification, KRAS Mutation P/N, KRAS Mutation OBSV, PTEN Stroma Manual Score, PTEN Tumor Manual Score, KRAS SCC and Stathmin H/L,Tissue.(Baseline and Cycle1 to Cycle 5 where each cycle consist of 28 days)
- Time for Cmax (Tmax) of PF-05212384 at Each Specified Time Points.(Pre-dose: 0 hours, and Post dose: 0.5 (after end of infusion), 1, 2, 4, 6, 24, 72, and 120 hours at Day 1)
- Clearance (CL) of PF-05212384 at Each Specified Time Points.(Pre-dose: 0 hours, and Post dose: 0.5 (after end of infusion), 1, 2, 4, 6, 24, 72, and 120 hours at Day 1)
- Number of Treatment-emergent Adverse Events (TEAEs) - All Causalities(From baseline (-3 days) until 35 days post last dose)
- Summary of Treatment-emergent Adverse Events (TEAEs) - All Causalities(From baseline (-3 days) until 35 days post last dose)
- Number of Treatment-related TEAEs(From baseline (-3 days) until 35 days post last dose)
- Summary of Treatment-related TEAEs(From baseline (-3 days) until 35 days post last dose)