Perioperative or Adjuvant mFOLFIRINOX for Resectable Pancreatic Cancer (PREOPANC-3)

• ClinicalTrials.gov Identifier: NCT04927780
• Recruitment Status: Recruiting
• First Posted: June 16, 2021
• Last Update Posted: August 15, 2023
• Sponsor: Erasmus Medical Center
• Collaborators: Dutch Pancreatic Cancer Group; Dutch Cancer Society
• Information provided by (Responsible Party): Bas Groot Koerkamp, MD, PhD, Erasmus Medical Center

Tracking Information

• First Submitted Date: June 8, 2021
• First Posted Date: June 16, 2021
• Last Update Posted Date: August 15, 2023
• Actual Study Start Date: September 7, 2021
• Estimated Primary Completion Date: February 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 15, 2021)

Overall survival [ Time Frame: Up to 5 years after randomization. ]

The time between randomization and death from any cause. Patients alive at last follow-up are censored.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 15, 2021)

• Progression free survival [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 4 months ]
  The percentage of patients who received at least one cycle of scheduled chemotherapy.
• Number of chemotherapy cycles received. [ Time Frame: 9 months ]
  The number of mFOLFIRINOX cycles patients received.
• Chemotherapy completion rate [ Time Frame: 9 months ]
  The percentage of patients who completed all cycles of scheduled chemotherapy.
• Dose intensity [ Time Frame: 9 months ]
  The amount of drug delivered as a percentage of planned dose according to the protocol.
• Staging laparoscopy rate [ Time Frame: At the time of surgery. ]
  The percentage of patients that actually underwent a staging laparoscopy, regardless whether a surgical exploration or resection was performed.
• Laparoscopy yield [ Time Frame: 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 [ Time Frame: At the time of surgery. ]
  The percentage of patients who underwent a surgical exploration (open or minimally-invasive), regardless whether a resection was performed.
• Resection rate [ Time Frame: At the time of surgery. ]
  The percentage of patients that underwent a curative-intent resection.
• Microscopically margin-negative (R0) resection rate [ Time Frame: 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.
• Lymph node-negative (N0) resection rate [ Time Frame: At the time of surgery. ]
  The percentage of patients that underwent a resection with negative lymph nodes (N0) in the surgical specimen.
• Pathologic response [ Time Frame: At the time of surgery. ]
  Tumor regression score in the surgical specimen
• Adverse events as assessed by the CTCAE version 5.0 [ Time Frame: Until 30 days after last chemotherapy. ]
  Adverse events are assessed during neoadjuvant therapy and adjuvant therapy.
• Postoperative complications [ Time Frame: 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 [ Time Frame: 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.
• Clinical response rate according to RECIST criteria version 1.1 [ Time Frame: At the time of surgery. ]
  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 [ Time Frame: Up to 5 years after randomization. ]
  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 [ Time Frame: Up to 5 years after randomization. ]
  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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: Up to 5 years after randomization. ]
  At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Perioperative or Adjuvant mFOLFIRINOX for Resectable Pancreatic Cancer
• Official Title: Perioperative Versus Adjuvant FOLFIRINOX for Resectable Pancreatic Cancer: the PREOPANC-3 Study

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 Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Pancreatic Cancer
• Pancreatic Ductal Adenocarcinoma
• Resectable Pancreatic Adenocarcinoma

Intervention

• Drug: Leucovorin Calcium
  IV
• Drug: Fluorouracil
  IV
• Drug: Irinotecan Hydrochloride
  IV
• Drug: Oxaliplatin
  IV
• Procedure: Resection
  Open or minimally-invasive pancreatectomy.

Study Arms

• Experimental: 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.
  Interventions:

  • Drug: Leucovorin Calcium
  • Drug: Fluorouracil
  • Drug: Irinotecan Hydrochloride
  • Drug: Oxaliplatin
  • Procedure: Resection
• Active Comparator: 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.
  Interventions:

  • Drug: Leucovorin Calcium
  • Drug: Fluorouracil
  • Drug: Irinotecan Hydrochloride
  • Drug: Oxaliplatin
  • Procedure: Resection

• Publications *: 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 15, 2021): 378
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2029
• Estimated Primary Completion Date: February 2026 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Study coordinator; +31 6 50032973; preopanc3@erasmusmc.nl

• Listed Location Countries: Netherlands, Norway, Sweden

Administrative Information

• NCT Number: NCT04927780
• Other Study ID Numbers: MEC-2021-0002; 2020-005141-16 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Yes

• Current Responsible Party: Bas Groot Koerkamp, MD, PhD, Erasmus Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Erasmus Medical Center
• Original Study Sponsor: Same as current

Collaborators

• Dutch Pancreatic Cancer Group
• Dutch Cancer Society

Investigators

• Principal Investigator: Bas Groot Koerkamp, MD, PhD; Erasmus MC University Medical Center

• PRS Account: Erasmus Medical Center
• Verification Date: August 2023