Perioperative Versus Adjuvant FOLFIRINOX for Resectable Pancreatic Cancer: the PREOPANC-3 Study
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 378
- 试验地点
- 43
- 主要终点
- Overall survival
研究概览
简要总结
The PREOPANC-3 study is a randomized, multicenter, phase 3 trial. Patients with resectable pancreatic cancer will be randomly assigned (1:1) to 8 cycles of neoadjuvant mFOLFIRINOX followed by surgery and 4 cycles of adjuvant mFOLFIRINOX (arm 1) or to upfront surgery followed by 12 cycles of adjuvant mFOLFIRINOX (arm 2).
The primary objective of the trial is to determine whether perioperative mFOLFIRINOX improves overall survival compared with adjuvant mFOLFIRINOX in patients with resectable pancreatic cancer.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically (Bethesda 5 or 6) confirmed pancreatic ductal adenocarcinoma.
- •Resectable tumor according to Dutch Pancreatic Cancer Group criteria: no arterial contact and venous contact with the superior mesenteric vein or portal vein of 90 degrees or less
- •No evidence for metastatic disease
- •WHO performance status of 0 or 1
- •Ability to undergo surgery and mFOLFIRINOX chemotherapy
- •Leucocytes (WBC) ≥ 3.0 x 10^9/L
- •Platelets ≥ 100 x 10^9/L
- •Hemoglobin ≥ 6.0 mmol/l
- •Renal function: eGFR ≥ 40 ml/min
- •Age ≥ 18 years
- •Written informed consent
排除标准
- •Prior radiotherapy, chemotherapy, or surgery for pancreatic cancer.
- •Prior chemotherapy precluding mFOLFIRINOX.
- •Previous malignancy (excluding non-melanoma skin cancer, pancreatic neuroendocrine tumor (pNET) <2cm, and gastrointestinal stromal tumor (GIST) <2cm), unless no evidence of disease and diagnosed more than 3 years before diagnosis of pancreatic cancer, or with a life expectancy of more than 5 years from date of inclusion.
- •Pregnancy or lactation.
- •Serious concomitant systemic disorders that would compromise the safety of the patient or his/her ability to complete the study, at the discretion of the investigator.
研究组 & 干预措施
Arm 1: Perioperative mFOLFIRINOX
Patients in the intervention arm (arm 1) start with neoadjuvant mFOLFIRINOX (consisting of oxaliplatin 85 mg/m², irinotecan 150 mg/m², leucovorin 400 mg/m², all at day 1, and fluorouracil continuous IV infusion 2.4 g/m² over 46 hours). Cycles are repeated every 14 days. After eight cycles, surgical resection is performed in the absence of unresectable or metastatic disease. After resection, four cycles of adjuvant mFOLFIRINOX are scheduled.
干预措施: Fluorouracil (Drug)
Arm 1: Perioperative mFOLFIRINOX
Patients in the intervention arm (arm 1) start with neoadjuvant mFOLFIRINOX (consisting of oxaliplatin 85 mg/m², irinotecan 150 mg/m², leucovorin 400 mg/m², all at day 1, and fluorouracil continuous IV infusion 2.4 g/m² over 46 hours). Cycles are repeated every 14 days. After eight cycles, surgical resection is performed in the absence of unresectable or metastatic disease. After resection, four cycles of adjuvant mFOLFIRINOX are scheduled.
干预措施: Leucovorin Calcium (Drug)
Arm 1: Perioperative mFOLFIRINOX
Patients in the intervention arm (arm 1) start with neoadjuvant mFOLFIRINOX (consisting of oxaliplatin 85 mg/m², irinotecan 150 mg/m², leucovorin 400 mg/m², all at day 1, and fluorouracil continuous IV infusion 2.4 g/m² over 46 hours). Cycles are repeated every 14 days. After eight cycles, surgical resection is performed in the absence of unresectable or metastatic disease. After resection, four cycles of adjuvant mFOLFIRINOX are scheduled.
干预措施: Resection (Procedure)
Arm 1: Perioperative mFOLFIRINOX
Patients in the intervention arm (arm 1) start with neoadjuvant mFOLFIRINOX (consisting of oxaliplatin 85 mg/m², irinotecan 150 mg/m², leucovorin 400 mg/m², all at day 1, and fluorouracil continuous IV infusion 2.4 g/m² over 46 hours). Cycles are repeated every 14 days. After eight cycles, surgical resection is performed in the absence of unresectable or metastatic disease. After resection, four cycles of adjuvant mFOLFIRINOX are scheduled.
干预措施: Oxaliplatin (Drug)
Arm 2: Adjuvant mFOLFIRINOX
Patients in the comparator arm (arm 2) start with surgery. After resection, 12 cycles of adjuvant mFOLFIRINOX (consisting of oxaliplatin 85 mg/m², irinotecan 150 mg/m², leucovorin 400 mg/m², all at day 1, and fluorouracil continuous IV infusion 2.4 g/m² over 46 hours) are scheduled.
干预措施: Leucovorin Calcium (Drug)
Arm 1: Perioperative mFOLFIRINOX
Patients in the intervention arm (arm 1) start with neoadjuvant mFOLFIRINOX (consisting of oxaliplatin 85 mg/m², irinotecan 150 mg/m², leucovorin 400 mg/m², all at day 1, and fluorouracil continuous IV infusion 2.4 g/m² over 46 hours). Cycles are repeated every 14 days. After eight cycles, surgical resection is performed in the absence of unresectable or metastatic disease. After resection, four cycles of adjuvant mFOLFIRINOX are scheduled.
干预措施: Irinotecan Hydrochloride (Drug)
Arm 2: Adjuvant mFOLFIRINOX
Patients in the comparator arm (arm 2) start with surgery. After resection, 12 cycles of adjuvant mFOLFIRINOX (consisting of oxaliplatin 85 mg/m², irinotecan 150 mg/m², leucovorin 400 mg/m², all at day 1, and fluorouracil continuous IV infusion 2.4 g/m² over 46 hours) are scheduled.
干预措施: Resection (Procedure)
Arm 2: Adjuvant mFOLFIRINOX
Patients in the comparator arm (arm 2) start with surgery. After resection, 12 cycles of adjuvant mFOLFIRINOX (consisting of oxaliplatin 85 mg/m², irinotecan 150 mg/m², leucovorin 400 mg/m², all at day 1, and fluorouracil continuous IV infusion 2.4 g/m² over 46 hours) are scheduled.
干预措施: Oxaliplatin (Drug)
Arm 2: Adjuvant mFOLFIRINOX
Patients in the comparator arm (arm 2) start with surgery. After resection, 12 cycles of adjuvant mFOLFIRINOX (consisting of oxaliplatin 85 mg/m², irinotecan 150 mg/m², leucovorin 400 mg/m², all at day 1, and fluorouracil continuous IV infusion 2.4 g/m² over 46 hours) are scheduled.
干预措施: Irinotecan Hydrochloride (Drug)
Arm 2: Adjuvant mFOLFIRINOX
Patients in the comparator arm (arm 2) start with surgery. After resection, 12 cycles of adjuvant mFOLFIRINOX (consisting of oxaliplatin 85 mg/m², irinotecan 150 mg/m², leucovorin 400 mg/m², all at day 1, and fluorouracil continuous IV infusion 2.4 g/m² over 46 hours) are scheduled.
干预措施: Fluorouracil (Drug)
结局指标
主要结局
Overall survival
时间窗: Up to 5 years after randomization.
The time between randomization and death from any cause. Patients alive at last follow-up are censored.
次要结局
- Staging laparoscopy rate(At the time of surgery.)
- Lymph node-negative (N0) resection rate(At the time of surgery.)
- Pathologic response(At the time of surgery.)
- Adverse events as assessed by the CTCAE version 5.0(Until 30 days after last chemotherapy.)
- Postoperative complications(Up to 90 days after surgery.)
- Serum CA 19-9 and CEA response(9 months)
- Progression free survival(Up to 5 years after randomization.)
- Distant metastases free survival(Up to 5 years after randomization.)
- Locoregional progression free survival(Up to 5 years after randomization.)
- Distant metastases free interval(Up to 5 years after randomization.)
- Locoregional progression free interval(Up to 5 years after randomization.)
- Chemotherapy start rate(4 months)
- Number of chemotherapy cycles received.(9 months)
- Chemotherapy completion rate(9 months)
- Dose intensity(9 months)
- Patient reported cancer-specific health-related Quality of Life (HRQoL) as assessed using the EORTC QLQ-C30(Up to 5 years after randomization.)
- Patient reported Quality of Life as assessed using Exocrine Pancreatic Insufficiency (EPI) questionnaire(Up to 5 years after randomization.)
- Laparoscopy yield(At the time of surgery.)
- Surgical exploration rate(At the time of surgery.)
- Microscopically margin-negative (R0) resection rate(At the time of surgery.)
- Patient reported Quality of Life as assessed using the worry of progression of cancer scale (WOPS)(Up to 5 years after randomization.)
- Patient reported Quality of Life as assessed using the happiness, hospital, anxiety and depression scale (HADS)(Up to 5 years after randomization.)
- Resection rate(At the time of surgery.)
- Patient reported non-disease specific HRQoL as assessed using the EQ-5D-5L(Up to 5 years after randomization.)
- Clinical response rate according to RECIST criteria version 1.1(At the time of surgery.)
- Patient reported tumor-specific HRQoL as assessed using the EORTC LQPAN26(Up to 5 years after randomization.)
- Patient reported chemotherapy-induced peripheral neuropathy as assessed using the EORTC QLQ-CIPN20(Up to 5 years after randomization.)
研究者
Bas Groot Koerkamp, MD, PhD
Principal Investigator
Erasmus Medical Center