Back to resultsPerioperative or Adjuvant mFOLFIRINOX for Resectable Pancreatic Cancer (PREOPANC-3)
Primary Purpose
Pancreatic Cancer, Pancreatic Ductal Adenocarcinoma, Resectable Pancreatic Adenocarcinoma
Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Leucovorin Calcium
Fluorouracil
Irinotecan Hydrochloride
Oxaliplatin
Resection
Sponsored by
About this trial
This is an interventional treatment trial for Pancreatic Cancer focused on measuring Neoadjuvant Therapy, Adjuvant Chemotherapy, Oxaliplatin, Irinotecan, Leucovorin, Fluorouracil, Pancreatic Neoplasms, Pancreatectomy
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
Sites / Locations
- Jeroen Bosch HospitalRecruiting
- Meander Medical CenterRecruiting
- Amsterdam UMCRecruiting
- OLVGRecruiting
- Amphia HospitalRecruiting
- Deventer HospitalRecruiting
- Catharina HospitalRecruiting
- Medisch Spectrum TwenteRecruiting
- University Medical Center GroningenRecruiting
- Tjongerschans HospitalRecruiting
- Medical Center LeeuwardenRecruiting
- Leiden University Medical CenterRecruiting
- Maastricht UMC+Recruiting
- Radboud University Medical CenterRecruiting
- Erasmus MC University Medical CenterRecruiting
- Maasstad ZiekenhuisRecruiting
- Regional Academic Center Utrecht, Antonius HospitalRecruiting
- Isala HospitalRecruiting
- Oslo University Hospital
- Sahlgrenska University HospitalRecruiting
- Skåne University HospitalRecruiting
- Karolinska University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Arm 1: Perioperative mFOLFIRINOX
Arm 2: Adjuvant mFOLFIRINOX
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Overall survival
The time between randomization and death from any cause. Patients alive at last follow-up are censored.
Secondary Outcome Measures
Progression free survival
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
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
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
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
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
The percentage of patients who received at least one cycle of scheduled chemotherapy.
Number of chemotherapy cycles received.
The number of mFOLFIRINOX cycles patients received.
Chemotherapy completion rate
The percentage of patients who completed all cycles of scheduled chemotherapy.
Dose intensity
The amount of drug delivered as a percentage of planned dose according to the protocol.
Staging laparoscopy rate
The percentage of patients that actually underwent a staging laparoscopy, regardless whether a surgical exploration or resection was performed.
Laparoscopy yield
The percentage of patients that underwent staging laparoscopy and were diagnosed with metastatic or unresectable disease during this procedure.
Surgical exploration rate
The percentage of patients who underwent a surgical exploration (open or minimally-invasive), regardless whether a resection was performed.
Resection rate
The percentage of patients that underwent a curative-intent resection.
Microscopically margin-negative (R0) resection rate
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.
Lymph node-negative (N0) resection rate
The percentage of patients that underwent a resection with negative lymph nodes (N0) in the surgical specimen.
Pathologic response
Tumor regression score in the surgical specimen
Adverse events as assessed by the CTCAE version 5.0
Adverse events are assessed during neoadjuvant therapy and adjuvant therapy.
Postoperative complications
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
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.
Clinical response rate according to RECIST criteria version 1.1
Response comparing baseline and restaging after 4 and 8 cycles of mFOLFIRINOX
Patient reported cancer-specific health-related Quality of Life (HRQoL) as assessed using the EORTC QLQ-C30
At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year
Patient reported non-disease specific HRQoL as assessed using the EQ-5D-5L
At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year
Patient reported tumor-specific HRQoL as assessed using the EORTC LQPAN26
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)
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
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)
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
At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year
Full Information
NCT ID
NCT04927780
First Posted
June 8, 2021
Last Updated
August 11, 2023
Sponsor
Erasmus Medical Center
Collaborators
Dutch Pancreatic Cancer Group, Dutch Cancer Society
1. Study Identification
Unique Protocol Identification Number
NCT04927780
Brief Title
Perioperative or Adjuvant mFOLFIRINOX for Resectable Pancreatic Cancer
Acronym
PREOPANC-3
Official Title
Perioperative Versus Adjuvant FOLFIRINOX for Resectable Pancreatic Cancer: the PREOPANC-3 Study
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 7, 2021 (Actual)
Primary Completion Date
February 2026 (Anticipated)
Study Completion Date
July 2029 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Erasmus Medical Center
Collaborators
Dutch Pancreatic Cancer Group, Dutch Cancer Society
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer, Pancreatic Ductal Adenocarcinoma, Resectable Pancreatic Adenocarcinoma
Keywords
Neoadjuvant Therapy, Adjuvant Chemotherapy, Oxaliplatin, Irinotecan, Leucovorin, Fluorouracil, Pancreatic Neoplasms, Pancreatectomy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
378 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Arm 1: Perioperative mFOLFIRINOX
Arm Type
Experimental
Arm Description
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 Title
Arm 2: Adjuvant mFOLFIRINOX
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Leucovorin Calcium
Intervention Description
IV
Intervention Type
Drug
Intervention Name(s)
Fluorouracil
Intervention Description
IV
Intervention Type
Drug
Intervention Name(s)
Irinotecan Hydrochloride
Intervention Description
IV
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Description
IV
Intervention Type
Procedure
Intervention Name(s)
Resection
Intervention Description
Open or minimally-invasive pancreatectomy.
Primary Outcome Measure Information:
Title
Overall survival
Description
The time between randomization and death from any cause. Patients alive at last follow-up are censored.
Time Frame
Up to 5 years after randomization.
Secondary Outcome Measure Information:
Title
Progression free survival
Description
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.
Time Frame
Up to 5 years after randomization.
Title
Distant metastases free survival
Description
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.
Time Frame
Up to 5 years after randomization.
Title
Locoregional progression free survival
Description
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.
Time Frame
Up to 5 years after randomization.
Title
Distant metastases free interval
Description
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.
Time Frame
Up to 5 years after randomization.
Title
Locoregional progression free interval
Description
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.
Time Frame
Up to 5 years after randomization.
Title
Chemotherapy start rate
Description
The percentage of patients who received at least one cycle of scheduled chemotherapy.
Time Frame
4 months
Title
Number of chemotherapy cycles received.
Description
The number of mFOLFIRINOX cycles patients received.
Time Frame
9 months
Title
Chemotherapy completion rate
Description
The percentage of patients who completed all cycles of scheduled chemotherapy.
Time Frame
9 months
Title
Dose intensity
Description
The amount of drug delivered as a percentage of planned dose according to the protocol.
Time Frame
9 months
Title
Staging laparoscopy rate
Description
The percentage of patients that actually underwent a staging laparoscopy, regardless whether a surgical exploration or resection was performed.
Time Frame
At the time of surgery.
Title
Laparoscopy yield
Description
The percentage of patients that underwent staging laparoscopy and were diagnosed with metastatic or unresectable disease during this procedure.
Time Frame
At the time of surgery.
Title
Surgical exploration rate
Description
The percentage of patients who underwent a surgical exploration (open or minimally-invasive), regardless whether a resection was performed.
Time Frame
At the time of surgery.
Title
Resection rate
Description
The percentage of patients that underwent a curative-intent resection.
Time Frame
At the time of surgery.
Title
Microscopically margin-negative (R0) resection rate
Description
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.
Time Frame
At the time of surgery.
Title
Lymph node-negative (N0) resection rate
Description
The percentage of patients that underwent a resection with negative lymph nodes (N0) in the surgical specimen.
Time Frame
At the time of surgery.
Title
Pathologic response
Description
Tumor regression score in the surgical specimen
Time Frame
At the time of surgery.
Title
Adverse events as assessed by the CTCAE version 5.0
Description
Adverse events are assessed during neoadjuvant therapy and adjuvant therapy.
Time Frame
Until 30 days after last chemotherapy.
Title
Postoperative complications
Description
According to the Clavien-Dindo classification and by the International Study Group of Pancreatic Surgery and International Study Group of Liver Surgery.
Time Frame
Up to 90 days after surgery.
Title
Serum CA 19-9 and CEA response
Description
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.
Time Frame
9 months
Title
Clinical response rate according to RECIST criteria version 1.1
Description
Response comparing baseline and restaging after 4 and 8 cycles of mFOLFIRINOX
Time Frame
At the time of surgery.
Title
Patient reported cancer-specific health-related Quality of Life (HRQoL) as assessed using the EORTC QLQ-C30
Description
At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year
Time Frame
Up to 5 years after randomization.
Title
Patient reported non-disease specific HRQoL as assessed using the EQ-5D-5L
Description
At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year
Time Frame
Up to 5 years after randomization.
Title
Patient reported tumor-specific HRQoL as assessed using the EORTC LQPAN26
Description
At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year
Time Frame
Up to 5 years after randomization.
Title
Patient reported Quality of Life as assessed using the worry of progression of cancer scale (WOPS)
Description
At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year
Time Frame
Up to 5 years after randomization.
Title
Patient reported chemotherapy-induced peripheral neuropathy as assessed using the EORTC QLQ-CIPN20
Description
At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year
Time Frame
Up to 5 years after randomization.
Title
Patient reported Quality of Life as assessed using the happiness, hospital, anxiety and depression scale (HADS)
Description
At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year
Time Frame
Up to 5 years after randomization.
Title
Patient reported Quality of Life as assessed using Exocrine Pancreatic Insufficiency (EPI) questionnaire
Description
At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year
Time Frame
Up to 5 years after randomization.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Study coordinator
Phone
+31 6 50032973
Email
preopanc3@erasmusmc.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bas Groot Koerkamp, MD, PhD
Organizational Affiliation
Erasmus MC University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Jeroen Bosch Hospital
City
's-Hertogenbosch
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Meander Medical Center
City
Amersfoort
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Amsterdam UMC
City
Amsterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
OLVG
City
Amsterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Amphia Hospital
City
Breda
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Deventer Hospital
City
Deventer
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Catharina Hospital
City
Eindhoven
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Medisch Spectrum Twente
City
Enschede
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
University Medical Center Groningen
City
Groningen
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Tjongerschans Hospital
City
Heerenveen
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Medical Center Leeuwarden
City
Leeuwarden
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Leiden University Medical Center
City
Leiden
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Maastricht UMC+
City
Maastricht
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Radboud University Medical Center
City
Nijmegen
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Erasmus MC University Medical Center
City
Rotterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Maasstad Ziekenhuis
City
Rotterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Regional Academic Center Utrecht, Antonius Hospital
City
Utrecht
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Isala Hospital
City
Zwolle
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Oslo University Hospital
City
Oslo
Country
Norway
Individual Site Status
Not yet recruiting
Facility Name
Sahlgrenska University Hospital
City
Gothenburg
Country
Sweden
Individual Site Status
Recruiting
Facility Name
Skåne University Hospital
City
Lund
Country
Sweden
Individual Site Status
Recruiting
Facility Name
Karolinska University Hospital
City
Stockholm
Country
Sweden
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
Citations:
PubMed Identifier
37550634
Citation
van Dam JL, Verkolf EMM, Dekker EN, Bonsing BA, Bratlie SO, Brosens LAA, Busch OR, van Driel LMJW, van Eijck CHJ, Feshtali S, Ghorbani P, de Groot DJA, de Groot JWB, Haberkorn BCM, de Hingh IH, van der Holt B, Karsten TM, van der Kolk MB, Labori KJ, Liem MSL, Loosveld OJL, Molenaar IQ, Polee MB, van Santvoort HC, de Vos-Geelen J, Wumkes ML, van Tienhoven G, Homs MYV, Besselink MG, Wilmink JW, Groot Koerkamp B; Dutch Pancreatic Cancer Group. Perioperative or adjuvant mFOLFIRINOX for resectable pancreatic cancer (PREOPANC-3): study protocol for a multicenter randomized controlled trial. BMC Cancer. 2023 Aug 7;23(1):728. doi: 10.1186/s12885-023-11141-5.
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Perioperative or Adjuvant mFOLFIRINOX for Resectable Pancreatic Cancer
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