Clinical trial NCT04927780: Perioperative or Adjuvant mFOLFIRINOX for Resectable Pancreatic Cancer
Official title: Perioperative Versus Adjuvant FOLFIRINOX for Resectable Pancreatic Cancer: the PREOPANC-3 Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Pancreatic Cancer
Pancreatic Ductal Adenocarcinoma
Resectable Pancreatic Adenocarcinoma
Keywords: Neoadjuvant Therapy
Adjuvant Chemotherapy
Oxaliplatin
Irinotecan
Leucovorin
Fluorouracil
Pancreatic Neoplasms
Pancreatectomy
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
Collaborators: name: Dutch Pancreatic Cancer Group
name: Dutch Cancer Society
First posted: 2021-06-16
Enrollment: 378
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Overall survival
timeFrame: Up to 5 years after randomization.
Secondary outcomes:
measure: Progression free survival
timeFrame: Up to 5 years after randomization.
measure: Distant metastases free survival
timeFrame: Up to 5 years after randomization.
measure: Locoregional progression free survival
timeFrame: Up to 5 years after randomization.
measure: Distant metastases free interval
timeFrame: Up to 5 years after randomization.
measure: Locoregional progression free interval
timeFrame: Up to 5 years after randomization.
measure: Chemotherapy start rate
timeFrame: 4 months
measure: Number of chemotherapy cycles received.
timeFrame: 9 months
measure: Chemotherapy completion rate
timeFrame: 9 months
measure: Dose intensity
timeFrame: 9 months
measure: Staging laparoscopy rate
timeFrame: At the time of surgery.
measure: Laparoscopy yield
timeFrame: At the time of surgery.
measure: Surgical exploration rate
timeFrame: At the time of surgery.
measure: Resection rate
timeFrame: At the time of surgery.
measure: Microscopically margin-negative (R0) resection rate
timeFrame: At the time of surgery.
measure: Lymph node-negative (N0) resection rate
timeFrame: At the time of surgery.
measure: Pathologic response
timeFrame: At the time of surgery.
measure: Adverse events as assessed by the CTCAE version 5.0
timeFrame: Until 30 days after last chemotherapy.
measure: Postoperative complications
timeFrame: Up to 90 days after surgery.
measure: Serum CA 19-9 and CEA response
timeFrame: 9 months
measure: Clinical response rate according to RECIST criteria version 1.1
timeFrame: At the time of surgery.
measure: Patient reported cancer-specific health-related Quality of Life (HRQoL) as assessed using the EORTC QLQ-C30
timeFrame: Up to 5 years after randomization.
measure: Patient reported non-disease specific HRQoL as assessed using the EQ-5D-5L
timeFrame: Up to 5 years after randomization.
measure: Patient reported tumor-specific HRQoL as assessed using the EORTC LQPAN26
timeFrame: Up to 5 years after randomization.
measure: Patient reported Quality of Life as assessed using the worry of progression of cancer scale (WOPS)
timeFrame: Up to 5 years after randomization.
measure: Patient reported chemotherapy-induced peripheral neuropathy as assessed using the EORTC QLQ-CIPN20
timeFrame: Up to 5 years after randomization.
measure: Patient reported Quality of Life as assessed using the happiness, hospital, anxiety and depression scale (HADS)
timeFrame: Up to 5 years after randomization.
measure: Patient reported Quality of Life as assessed using Exocrine Pancreatic Insufficiency (EPI) questionnaire
timeFrame: Up to 5 years after randomization.
Other outcomes:
Locations:
city: 's-Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Hospital
city: Amersfoort
country: Netherlands
facility: Meander Medical Center
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
city: Amsterdam
country: Netherlands
facility: OLVG
city: Breda
country: Netherlands
facility: Amphia Hospital
city: Deventer
country: Netherlands
facility: Deventer Hospital
city: Eindhoven
country: Netherlands
facility: Catharina Hospital
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Heerenveen
country: Netherlands
facility: Tjongerschans Hospital
city: Leeuwarden
country: Netherlands
facility: Medical Center Leeuwarden
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Maastricht
country: Netherlands
facility: Maastricht UMC+
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus MC University Medical Center
city: Rotterdam
country: Netherlands
facility: Maasstad Ziekenhuis
city: Utrecht
country: Netherlands
facility: Regional Academic Center Utrecht, Antonius Hospital
city: Zwolle
country: Netherlands
facility: Isala Hospital
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
city: Lund
country: Sweden
facility: Skåne University Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
Study officials:
affiliation: Erasmus MC University Medical Center
name: Bas Groot Koerkamp, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.