A Randomized, Multicenter, Double-blind, Placebo-controlled, Phase 3 Study of the Bruton's Tyrosine Kinase Inhibitor Ibrutinib in Combination With Nab-paclitaxel and Gemcitabine Versus Placebo in Combination With Nab-paclitaxel and Gemcitabine, in the First Line Treatment of Patients With Metastatic Pancreatic Adenocarcinoma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 430
- 试验地点
- 86
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
This is a phase 3 study to evaluate the efficacy of ibrutinib in combination with nab-paclitaxel and gemcitabine for the first line treatment of patients with metastatic pancreatic adenocarcinoma.
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
- •Histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma.
- •Stage IV disease diagnosed within 6 weeks of randomization
- •Adequate hematologic function:
- •Absolute neutrophil count (ANC) ≥1.5 x 109/L
- •Platelet count ≥100 x 109/L
- •Hemoglobin ≥9 g/dL
- •Adequate hepatic and renal function defined as:
- •AST and/or ALT ≤5.0 x upper limit of normal (ULN) if liver metastases, or ≤3 x ULN without liver metastases
- •Alkaline phosphatase <3.0 x ULN or ≤5.0 x ULN if liver or bone metastases present
- •Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin, such as hemolysis)
- •Estimated Creatinine Clearance ≥30 mL/min
- •PT/INR <1.5 x ULN and PTT (aPTT) <1.5 x ULN
- •Eastern Cooperative Oncology Group (ECOG) 0-1
排除标准
- •Prior therapies: BTK inhibitor, radiotherapy, radiotherapy in the adjuvant setting, or cytotoxic chemotherapy for primary disease of pancreatic adenocarcinoma.
- •Neuroendocrine (carcinoid, islet cell) or acinar pancreatic carcinoma
- •Known brain or leptomeningeal disease (CT or MRI scan of the brain required only in case of clinical suspicion of central nervous system involvement).
- •Major surgery within 4 weeks of first dose of study drug.
- •History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
- •Treatment with a strong cytochrome P450 (CYP) 3A inhibitor.
研究组 & 干预措施
Ibrutinib
Ibrutinib daily in combination with:
Nab-paclitaxel and gemcitabine
干预措施: Ibrutinib (Drug)
Ibrutinib
Ibrutinib daily in combination with:
Nab-paclitaxel and gemcitabine
干预措施: Gemcitabine (Drug)
Ibrutinib
Ibrutinib daily in combination with:
Nab-paclitaxel and gemcitabine
干预措施: Nab-paclitaxel (Drug)
Placebo
Placebo daily in combination with:
Nab-paclitaxel and gemcitabine
干预措施: Gemcitabine (Drug)
Placebo
Placebo daily in combination with:
Nab-paclitaxel and gemcitabine
干预措施: Nab-paclitaxel (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: Results at an overall median follow-up of 24.87 months
PFS is defined as the time from the date of randomization until disease progression per RECIST 1.1 criteria assessed by investigator, or death from any cause, whichever occurs first.
Overall Survival (OS)
时间窗: Results at an overall median follow-up of 24.87 months
OS, is defined as the time from date of randomization until date of death from any cause.
次要结局
- Clinical Benefit Response(Results at an overall median follow-up of 24.87 months)
- Patient-reported Outcome (PRO) by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30).(Results at an overall median follow-up of 24.87 months)
- Overall Response Rate(Results at an overall median follow-up of 24.87 months)
- Rate of Venous Thromboembolic Events (VTE)(Results at an overall median follow-up of 24.87 months)
- Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Nab-paclitaxel and Gemcitabine Versus Placebo in Combination With Nab-paclitaxel and Gemcitabine.(Results at an overall median follow-up of 24.87 months)
- Carbohydrate Antigen 19-9 (CA19-9) Response(Results at an overall median follow-up of 24.87 months)