Perioperative or Adjuvant mFOLFIRINOX for Resectable Pancreatic Cancer

Pancreatic Cancer Clinical Trial

— PREOPANC-3  

Official title:

Perioperative Versus Adjuvant FOLFIRINOX for Resectable Pancreatic Cancer: the PREOPANC-3 Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04927780
• Other study ID #: MEC-2021-0002
• Secondary ID: 2020-005141-16
• Status: Recruiting
• Phase: Phase 3
• Start date: September 7, 2021
• Est. completion date: July 2029

Study information

• Verified date: August 2023
• Source: Erasmus Medical Center
• Contact: Study coordinator
• Phone: +31 6 50032973
• Email: preopanc3[@]erasmusmc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 378
• Est. completion date: July 2029
• Est. primary completion date: February 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Pancreatic Cancer
• Pancreatic Ductal Adenocarcinoma
• Pancreatic Neoplasms
• Resectable Pancreatic Adenocarcinoma

Intervention

Drug:
• Leucovorin Calcium
IV
• Fluorouracil
IV
• Irinotecan Hydrochloride
IV
• Oxaliplatin
IV

Procedure:
• Resection
Open or minimally-invasive pancreatectomy.

Locations

Country	Name	City	State
Netherlands	Jeroen Bosch Hospital	's-Hertogenbosch
Netherlands	Meander Medical Center	Amersfoort
Netherlands	Amsterdam UMC	Amsterdam
Netherlands	OLVG	Amsterdam
Netherlands	Amphia Hospital	Breda
Netherlands	Deventer Hospital	Deventer
Netherlands	Catharina Hospital	Eindhoven
Netherlands	Medisch Spectrum Twente	Enschede
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Tjongerschans Hospital	Heerenveen
Netherlands	Medical Center Leeuwarden	Leeuwarden
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Maastricht UMC+	Maastricht
Netherlands	Radboud University Medical Center	Nijmegen
Netherlands	Erasmus MC University Medical Center	Rotterdam
Netherlands	Maasstad Ziekenhuis	Rotterdam
Netherlands	Regional Academic Center Utrecht, Antonius Hospital	Utrecht
Netherlands	Isala Hospital	Zwolle
Norway	Oslo University Hospital	Oslo
Sweden	Sahlgrenska University Hospital	Gothenburg
Sweden	Skåne University Hospital	Lund
Sweden	Karolinska University Hospital	Stockholm

Sponsors (3)

Lead Sponsor	Collaborator
Erasmus Medical Center	Dutch Cancer Society, Dutch Pancreatic Cancer Group

Countries where clinical trial is conducted

Netherlands,  Norway,  Sweden, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	The time between randomization and death from any cause. Patients alive at last follow-up are censored.	Up to 5 years after randomization.
Secondary	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.	Up to 5 years after randomization.
Secondary	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.	Up to 5 years after randomization.
Secondary	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.	Up to 5 years after randomization.
Secondary	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.	Up to 5 years after randomization.
Secondary	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.	Up to 5 years after randomization.
Secondary	Chemotherapy start rate	The percentage of patients who received at least one cycle of scheduled chemotherapy.	4 months
Secondary	Number of chemotherapy cycles received.	The number of mFOLFIRINOX cycles patients received.	9 months
Secondary	Chemotherapy completion rate	The percentage of patients who completed all cycles of scheduled chemotherapy.	9 months
Secondary	Dose intensity	The amount of drug delivered as a percentage of planned dose according to the protocol.	9 months
Secondary	Staging laparoscopy rate	The percentage of patients that actually underwent a staging laparoscopy, regardless whether a surgical exploration or resection was performed.	At the time of surgery.
Secondary	Laparoscopy yield	The percentage of patients that underwent staging laparoscopy and were diagnosed with metastatic or unresectable disease during this procedure.	At the time of surgery.
Secondary	Surgical exploration rate	The percentage of patients who underwent a surgical exploration (open or minimally-invasive), regardless whether a resection was performed.	At the time of surgery.
Secondary	Resection rate	The percentage of patients that underwent a curative-intent resection.	At the time of surgery.
Secondary	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.	At the time of surgery.
Secondary	Lymph node-negative (N0) resection rate	The percentage of patients that underwent a resection with negative lymph nodes (N0) in the surgical specimen.	At the time of surgery.
Secondary	Pathologic response	Tumor regression score in the surgical specimen	At the time of surgery.
Secondary	Adverse events as assessed by the CTCAE version 5.0	Adverse events are assessed during neoadjuvant therapy and adjuvant therapy.	Until 30 days after last chemotherapy.
Secondary	Postoperative complications	According to the Clavien-Dindo classification and by the International Study Group of Pancreatic Surgery and International Study Group of Liver Surgery.	Up to 90 days after surgery.
Secondary	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.	9 months
Secondary	Clinical response rate according to RECIST criteria version 1.1	Response comparing baseline and restaging after 4 and 8 cycles of mFOLFIRINOX	At the time of surgery.
Secondary	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	Up to 5 years after randomization.
Secondary	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	Up to 5 years after randomization.
Secondary	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	Up to 5 years after randomization.
Secondary	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	Up to 5 years after randomization.
Secondary	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	Up to 5 years after randomization.
Secondary	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	Up to 5 years after randomization.
Secondary	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	Up to 5 years after randomization.