Phase 1b Study Of Docetaxel + Pf 03084014 In Metastatic Or Locally Recurrent/Advanced Triple Negative Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 30
- 试验地点
- 15
- 主要终点
- Progression-free Survival (PFS) at 6 Months - Expansion Cohort
研究概览
简要总结
This study is aimed to determine the tolerability of the PF-03084014 plus docetaxel combination in patients with advanced breast cancer. Preliminary information about the efficacy of the combination will also be collected.
研究设计
- 研究类型
- Interventional
- 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
- •Diagnosis of breast cancer with evidence of a) metastatic or b) locally recurrent/advanced disease.
排除标准
- •Prior treatment with a gamma secretase inhibitors or other Notch signaling inhibitors.
研究组 & 干预措施
PF-03084014 plus docetaxel
PF 03084014 will be administered orally, continuously, twice daily at doses from 80 to 150 mg in combination with docetaxel given every 3 weeks at doses from 75 to 100 mg/m^2
干预措施: PF-03084014 (Drug)
PF-03084014 plus docetaxel
PF 03084014 will be administered orally, continuously, twice daily at doses from 80 to 150 mg in combination with docetaxel given every 3 weeks at doses from 75 to 100 mg/m^2
干预措施: Docetaxel (Drug)
结局指标
主要结局
Progression-free Survival (PFS) at 6 Months - Expansion Cohort
时间窗: Baseline till 6 months post-dose
The period from study entry until disease progression, death or date of last contact. Assessment of response was made using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Number of Participants With Dose-limiting Toxicities (DLTs) in Cycle 1
时间窗: Cycle 1 Days 1-21
Any DLT event in Cycle 1: Grade 4 neutropenia lasting more than (\>)7 days; febrile neutropenia (Grade more than or equal to \[\>=\] 3 and body temperature \>=38.5 degrees Celsius); Grade \>=3 neutropenic infection; Grade \>=3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia without bleeding; Grade \>=3 toxicities (except those that had not been maximally treated); Grade 3 prolongation of time from electrocardiogram (ECG) Q wave to the end of the T wave corresponding to electrical systole (QT) corrected for heart rate (QTc) which persisted after correction of reversible causes; delay of 2 weeks in receiving next scheduled cycle due to persisting treatment-related toxicities; and failure to deliver at least 80% of planned dose during first cycle due to treatment-related toxicities.
次要结局
- Number of Participants With All Causality and Treatment-related Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Withdrawals Due to TEAEs(Baseline up to 28-35 days after treatment discontinuation (up to Day 280))
- Maximum Serum or Plasma Concentration (Cmax) and Predose Concentration (Ctrough) of PF-03084014 in Dose-finding Cohort(C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12))
- Tmax of PF-03084014 in the Expansion Cohort(C1D1, C1D21, and Day 1 of subsequent cycles and at EOT (max reached: C12))
- Number of Participants With Laboratory Abnormalities(Baseline up to 28-35 days after treatment discontinuation (up to Day 280))
- Volume of Distribution (Vss) of Docetaxel in Dose-finding Cohort(C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12))
- AUClast of PF-03084014 in the Expansion Cohort(C1D1, C1D21, and Day 1 of subsequent cycles and at EOT (max reached: C12))
- Percentage Change From Baseline in Notch 1 to 4 Ribonucleic Acid (RNA) in Blood(C1D1, C1D2, C1D8, C1D21 and EOT (maximum reached: C12))
- Time to Cmax (Tmax) of PF-03084014 in Dose-finding Cohort(C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12))
- Tmax of Docetaxel in Dose-finding Cohort(C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12))
- Terminal Half-life (t1/2) of Docetaxel in Dose-finding Cohort(C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12))
- Cmax of PF-03084014 in the Expansion Cohort(C1D1, C1D21, and Day 1 of subsequent cycles and at EOT (max reached: C12))
- Cmax of Docetaxel in Dose-finding Cohort(C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12))
- Systemic Clearance (CL) of Docetaxel in Dose-finding Cohort(C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12))
- Ctrough of PF-03084014 in the Expansion Cohort(C1D1, C1D21, and Day 1 of subsequent cycles and at EOT (max reached: C12))
- Percentage of Participants With Objective Response (OR)(Baseline, every 6 weeks from Cycle 2 onwards up to 26 months)
- Area Under the Concentration-time Curve (AUC) From Time 0 to Time of Last Measured Concentration (AUClast) of PF-03084014 in Dose-finding Cohort(Cycle (C) 1 Days (D) 1, 2, 8, and 21; Day 1 of subsequent cycles and at EOT (max reached: Cycle 12))
- AUClast and AUC From Time 0 Extrapolated to Infinite Time (AUCinf) of Docetaxel in Dose-finding Cohort(C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12))
- Duration of Response (DR)(Baseline up to 28-35 days after treatment discontinuation (up to Day 280))
- Number of Participants With QTc Values Meeting Categorical Summarization Criteria(Screening, C1D1, C1D21, Day 1 of subsequent cycles, and EOT (maximum reached: C12))