Perioperative or Adjuvant mFOLFIRINOX for Resectable Pancreatic Cancer
- Conditions
- Pancreatic CancerPancreatic Ductal AdenocarcinomaResectable Pancreatic Adenocarcinoma
- Interventions
- Registration Number
- NCT04927780
- Lead Sponsor
- Erasmus Medical Center
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 378
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1: Perioperative mFOLFIRINOX Leucovorin Calcium 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. Arm 1: Perioperative mFOLFIRINOX Resection 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. Arm 2: Adjuvant mFOLFIRINOX Leucovorin Calcium 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. Arm 2: Adjuvant mFOLFIRINOX Resection 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. Arm 2: Adjuvant mFOLFIRINOX Irinotecan Hydrochloride 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. Arm 1: Perioperative mFOLFIRINOX Oxaliplatin 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. Arm 1: Perioperative mFOLFIRINOX Fluorouracil 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. Arm 1: Perioperative mFOLFIRINOX Irinotecan Hydrochloride 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. Arm 2: Adjuvant mFOLFIRINOX Fluorouracil 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. Arm 2: Adjuvant mFOLFIRINOX Oxaliplatin 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.
- Primary Outcome Measures
Name Time Method Overall survival Up to 5 years after randomization. The time between randomization and death from any cause. Patients alive at last follow-up are censored.
- Secondary Outcome Measures
Name Time Method Staging laparoscopy rate At the time of surgery. The percentage of patients that actually underwent a staging laparoscopy, regardless whether a surgical exploration or resection was performed.
Lymph node-negative (N0) resection rate At the time of surgery. The percentage of patients that underwent a resection with negative lymph nodes (N0) in the surgical specimen.
Pathologic response At the time of surgery. Tumor regression score in the surgical specimen
Adverse events as assessed by the CTCAE version 5.0 Until 30 days after last chemotherapy. Adverse events are assessed during neoadjuvant therapy and adjuvant therapy.
Postoperative complications Up to 90 days after surgery. According to the Clavien-Dindo classification and by the International Study Group of Pancreatic Surgery and International Study Group of Liver Surgery.
Serum CA 19-9 and CEA response 9 months The change in carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) after surgery and after 4, 8, and 12 cycles of mFOLFIRINOX compared to baseline.
Progression free survival Up to 5 years after randomization. The time between randomization and locoregional progressive disease before or during treatment (resulting in irresectability), the occurrence of distant metastases, recurrent pancreatic cancer after surgery or death from any cause. Patients alive and free of these events at last follow-up are censored.
Distant metastases free survival Up to 5 years after randomization. The time between randomization and the occurrence of distant metastases or death from any cause. Patients alive and free of these events at last follow-up are censored.
Locoregional progression free survival Up to 5 years after randomization. The time between randomization and locoregional progression before or during treatment (resulting in irresectability), locoregional recurrence after resection or death from any cause. Patients alive and free of these events at last follow-up are censored.
Distant metastases free interval Up to 5 years after randomization. The time between randomization and the occurrence of distant metastases. Distant metastases are considered an event and patients are censored at death or last follow-up when without this event.
Locoregional progression free interval Up to 5 years after randomization. The time between randomization and locoregional progression before or during treatment (resulting in irresectability), or locoregional recurrence after resection. Locoregional progressive disease before or during treatment or locoregional recurrence after resection are considered an event and patients are censored at death or last follow-up when free of these events.
Chemotherapy start rate 4 months The percentage of patients who received at least one cycle of scheduled chemotherapy.
Number of chemotherapy cycles received. 9 months The number of mFOLFIRINOX cycles patients received.
Chemotherapy completion rate 9 months The percentage of patients who completed all cycles of scheduled chemotherapy.
Dose intensity 9 months The amount of drug delivered as a percentage of planned dose according to the protocol.
Patient reported cancer-specific health-related Quality of Life (HRQoL) as assessed using the EORTC QLQ-C30 Up to 5 years after randomization. At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year
Patient reported Quality of Life as assessed using Exocrine Pancreatic Insufficiency (EPI) questionnaire Up to 5 years after randomization. At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year
Resection rate At the time of surgery. The percentage of patients that underwent a curative-intent resection.
Laparoscopy yield At the time of surgery. The percentage of patients that underwent staging laparoscopy and were diagnosed with metastatic or unresectable disease during this procedure.
Surgical exploration rate At the time of surgery. The percentage of patients who underwent a surgical exploration (open or minimally-invasive), regardless whether a resection was performed.
Microscopically margin-negative (R0) resection rate At the time of surgery. The percentage of patients that underwent a microscopically margin-negative (R0) resection. The resection is considered R0 if there is no tumor within 1 mm of the margins.
Patient reported non-disease specific HRQoL as assessed using the EQ-5D-5L Up to 5 years after randomization. At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year
Patient reported Quality of Life as assessed using the worry of progression of cancer scale (WOPS) Up to 5 years after randomization. At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year
Patient reported Quality of Life as assessed using the happiness, hospital, anxiety and depression scale (HADS) Up to 5 years after randomization. At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year
Clinical response rate according to RECIST criteria version 1.1 At the time of surgery. Response comparing baseline and restaging after 4 and 8 cycles of mFOLFIRINOX
Patient reported tumor-specific HRQoL as assessed using the EORTC LQPAN26 Up to 5 years after randomization. At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year
Patient reported chemotherapy-induced peripheral neuropathy as assessed using the EORTC QLQ-CIPN20 Up to 5 years after randomization. At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year
Trial Locations
- Locations (22)
Amphia Hospital
🇳🇱Breda, Netherlands
Medisch Spectrum Twente
🇳🇱Enschede, Netherlands
Tjongerschans Hospital
🇳🇱Heerenveen, Netherlands
Skåne University Hospital
🇸🇪Lund, Sweden
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Medical Center Leeuwarden
🇳🇱Leeuwarden, Netherlands
Radboud University Medical Center
🇳🇱Nijmegen, Netherlands
Amsterdam UMC
🇳🇱Amsterdam, Netherlands
Meander Medical Center
🇳🇱Amersfoort, Netherlands
Deventer Hospital
🇳🇱Deventer, Netherlands
Isala Hospital
🇳🇱Zwolle, Netherlands
Maastricht UMC+
🇳🇱Maastricht, Netherlands
Maasstad Ziekenhuis
🇳🇱Rotterdam, Netherlands
Regional Academic Center Utrecht, Antonius Hospital
🇳🇱Utrecht, Netherlands
Jeroen Bosch Hospital
🇳🇱's-Hertogenbosch, Netherlands
OLVG
🇳🇱Amsterdam, Netherlands
Catharina Hospital
🇳🇱Eindhoven, Netherlands
Erasmus MC University Medical Center
🇳🇱Rotterdam, Netherlands
Leiden University Medical Center
🇳🇱Leiden, Netherlands
Oslo University Hospital
🇳🇴Oslo, Norway
Sahlgrenska University Hospital
🇸🇪Gothenburg, Sweden
Karolinska University Hospital
🇸🇪Stockholm, Sweden