PHASE 1/2 STUDY OF PF-03084014 IN COMBINATION WITH GEMCITABINE AND NAB-PACLITAXEL IN PATIENTS WITH PREVIOUSLY UNTREATED METASTATIC PANCREATIC DUCTAL ADENOCARCINOMA
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 3
- 试验地点
- 5
- 主要终点
- Number of Participants With Dose-limiting Toxicities (DLTs) in Cycle 1
研究概览
简要总结
This study consists of a Phase 1b portion aimed to determine the maximum tolerated dose and the safety profile of PF-03084014 in combination with gemcitabine and nab-paclitaxel followed by a Phase 2 portion to evaluate the efficacy of the triple combination in terms of overall survival in patients with metastatic pancreatic ductal adenocarcinoma not previously treated with anticancer therapies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 主要目的
- Treatment
- 盲法
- None
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
- •Histologically or cytologically diagnosis of metastatic ductal adenocarcinoma of the pancreas.
- •No prior radiotherapy, surgery chemotherapy or investigational therapy for metastatic disease. Prior adjuvant therapy with 5-FU or gemcitabine (± gemcitabine post radiation) administered as radiosensitizer allowed, provided at least 6 months have elapsed between the last dose and study registration
- •Tumor tissue available (Archival 6 months old or de novo biopsy)
- •Measurable disease as per RECIST 1.1
- •Performance Status (ECOG) 0 or 1
排除标准
- •Symptomatic brain metastases requiring steroids
- •Prior therapy with gamma secretase inhibitors or other Notch pathway inhibitor
- •Major surgery within 4 weeks of registration in the current study
- •Known hypersensitivity to gemcitabine or nab-paclitaxel or any of the excipients
- •Current or anticipated need for food or drugs that are strong/moderate CYP3A4 inhibitors or inducers
- •Diagnosis of any second malignancy within 3 years prior to registration
研究组 & 干预措施
Phase 1
PF-03084014 in combination with gemcitabine and nab-paclitaxel
干预措施: PF-03084014 (Drug)
Phase 1
PF-03084014 in combination with gemcitabine and nab-paclitaxel
干预措施: Gemcitabine (Drug)
Phase 1
PF-03084014 in combination with gemcitabine and nab-paclitaxel
干预措施: Nab-paclitaxel (Drug)
Phase 2 Arm A
PF-03084014 in combination with gemcitabine and nab-paclitaxel
干预措施: PF-03084014 (Drug)
Phase 2 Arm A
PF-03084014 in combination with gemcitabine and nab-paclitaxel
干预措施: Gemcitabine (Drug)
Phase 2 Arm A
PF-03084014 in combination with gemcitabine and nab-paclitaxel
干预措施: Nab-paclitaxel (Drug)
Phase 2 Arm B
Gemcitabine plus nab-Paclitaxel
干预措施: Gemcitabine (Drug)
Phase 2 Arm B
Gemcitabine plus nab-Paclitaxel
干预措施: Nab-paclitaxel (Drug)
结局指标
主要结局
Number of Participants With Dose-limiting Toxicities (DLTs) in Cycle 1
时间窗: Cycle 1 (28 days)
DLT was defined as any of the following events occurring during the first cycle of treatment and considered at least possibly-related to study medication: any Grade 3 or 4 clinically-relevant non-hematologic and/or hematologic toxicity, delay of more than 2 weeks in receiving the next scheduled cycle due to persisting treatment-related toxicities.
Overall Survival (OS) in Phase 2
时间窗: From start of study treatment, collected every 3 months until death (up to 5 years)
Overall survival was the duration from randomization to death. For participants who are alive, overall survival was censored at the last contact.
次要结局
- Number of Participants With Adverse Events (AEs) by Seriousness and Relationship to Treatment in Phase 1(Baseline up to 28-35 days post last administration of study drug)
- Number of Participants With Laboratory Abnormalities in Phase 1(Screening; Cycle 1 Days 1, 8, 15, 22; up to 28-35 days post last administration of study drug)
- Number of Participants With Clinically Significant Change From Baseline in Vital Signs at Phases 1 and 2(Baseline up to 28-35 days after treatment discontinuation)
- Number of Participants With Adverse Events (AEs) by Seriousness and Relationship to Treatment in Phase 2(Baseline up to 28-35 days post last administration of study drug)
- Number of Participants With Laboratory Abnormalities in Phase 2(Screening; Days 1, 8, 15 of each cycle; up to 28-35 days post last administration of study drug)
- Number of Participants With Worsening QTc Results in Phase 1(Screening, Cycle 1 Days 3 and 22, Cycles 2 and 3 Day 1, end of treatment)
- Area Under the Concentration-time Curve (AUC) for PF-03084014, Nab-P and Gemcitabine in Phase 1(PF-03084014: Cycle 1 Days 3, 15, 22; Day 1 of subsequent cycles; and end of treatment. nab-P: Cycle 1 Days 1-3 and 15-17. Gemcitabine: Cycle 1 Days 1 and 15.)
- Area Under the Concentration-time Curve (AUC) for PF-03084014, Nab-P and Gemcitabine in Phase 2(Cycle 1 Day 1 till end of last cycle)
- Maximum Observed Plasma Concentration (Cmax) for PF-03084014, Nab-P and GEM in Phase 1(PF-03084014: Cycle 1 Days 3, 15, 22; Day 1 of subsequent cycles; and end of treatment. nab-P: Cycle 1 Days 1-3 and 15-17. Gemcitabine: Cycle 1 Days 1 and 15.)
- Number of Participants With Objective Response (OR) in Phase 2(Screening till 28-35 days post last administration of study drug)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-03084014, Nab-P and GEM in Phase 2(Cycle 1 Day 1 till end of last cycle)
- Volume of Distribution at Steady State (Vss) for PF-03084014, Nab-P and GEM in Phase 2(Cycle 1 Day 1 till end of last cycle)
- Plasma Decay Half-life (t1/2) for PF-03084014, Nab-P and GEM in Phase 2(Cycle 1 Day 1 till end of last cycle)
- Duration of Response (DR) for Phases 1 and 2(Baseline, every 8 weeks until disease progression or unacceptable toxicity (up to 5 years))
- 1-year and 2-year OS in Phase 2(From start of study treatment, collected every 3 months until death (up to 5 years))
- Brief Pain Inventory-Short Form (BPI-sf) Score - Phase 2(Day 1 of Cycle 1 and subsequent cycles; end of treatment)
- Change From Baseline in European Quality of Life Questionnaire (EQ-5D) - Phase 2(Baseline till end of treatment)
- Number of Participants With Worsening QTc Results in Phase 2(Screening, Cycle 1 Days 1 and 22, Cycles 2 and 3 Day 1, end of treatment)
- Systemic Clearance (CL) of PF-03084014, Nab-P and GEM in Phase 2(Cycle 1 Day 1 till end of last cycle)
- Volume of Distribution at Steady State (Vss) for Nab-P and GEM in Phase 1(Cycle 1 (Days 1 and 15 for gemcitabine; Days 1-3 and 15-17 for nab-paclitaxel))
- Maximum Observed Plasma Concentration (Cmax) for PF-03084014, Nab-P and GEM in Phase 2(Cycle 1 Day 1 till end of last cycle)
- Plasma Decay Half-life (t1/2) for Nab-P and GEM in Phase 1(Cycle 1 (Days 1 and 15 for gemcitabine; Days 1-3 and 15-17 for nab-paclitaxel))
- Progression-free Survival (PFS) in Phase 2(From start of study treatment, collected every 3 months until death (up to 5 years))
- Systemic Clearance (CL) of Nab-paclitaxel in Phase 1(Cycle 1 Days 1-3, and 15-17)
- Systemic Clearance (CL) of Gemcitabine in Phase 1(Cycle 1 Days 1 and 15)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-03084014, Nab-P and GEM in Phase 1(PF-03084014: Cycle 1 Days 3, 15, 22; Day 1 of subsequent cycles; and end of treatment. nab-P: Cycle 1 Days 1-3 and 15-17. Gemcitabine: Cycle 1 Days 1 and 15.)
- Number of Participants With Objective Response (OR) in Phase 1(Screening till 28-35 days post last administration of study drug)
- European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire (EORTC QLQ-C30) - Phase 2(Baseline till end of treatment)