Neoadjuvant Triple Therapy for (Borderline) Resectable Pancreatic Cancer (PREOPANC-5) (PREOPANC-5)

February 10, 2026 updated by: Trial Office Medical Oncology VUmc, Amsterdam UMC, location VUmc

Neoadjuvant Triple Treatment With mFOLFIRINOX, Pembrolizumab and SABR in Patients With (Borderline) Resectable Pancreatic Cancer (PREOPANC-5): a Multicenter Single Arm Phase Ib/II Trial of the Dutch Pancreatic Cancer Group

Since patients with (borderline) resectable pancreatic cancer have a limited life expectancy, it is important to improve treatment strategies. Therefore, the objective of this study is to investigate whether neoadjuvant triple treatment with chemotherapy (mFOLFIRINOX), immunotherapy (pembrolizumab and stereotactic radiotherapy, followed by adjuvant surgery and chemotherapy and immunotherapy, improves survival in patients with (borderline) resectabel pancreatic cancer.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

66

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Netherlands
      • Amsterdam, Netherlands
        • Recruiting
        • Amsterdam University Medical Center
        • Contact:
      • Maastricht, Netherlands
        • Not yet recruiting
        • Maastricht University Medical Center
        • Contact:
      • Nieuwegein, Netherlands
      • Rotterdam, Netherlands
        • Recruiting
        • Erasmus University Medical Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed adenocarcinoma of the pancreas (WHO VI or VII)
  • Male or female participants who are at least 18 years of age on the day of signing informed consent
  • Primary resectable or borderline resectable disease (DPCG criteria)
  • ECOG performance status 0 or 1
  • Ability to undergo surgery, radiotherapy, chemotherapy and immunotherapy
  • Leucocytes (WBC) ≥ 3.0 X 10*9/l, Platelets ≥ 100X 10*9 /l, Hemoglobin ≥ 6 mmol/l, Renal function: E-GFR > 50 ml/min, Bilirubin < 50 µmol/l or planned for biliary drainage
  • A male participant must agree to use a contraception as detailed in Appendix 6 of this protocol during the treatment period and for at least 18 weeks after the last dose of study treatment and refrain from donating sperm during this period.
  • A female participant is eligible to participate if she is not pregnant (see Appendix 6), not breastfeeding, and at least one of the following conditions applies: Not a:

woman of childbearing potential (WOCBP) OR WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 18 weeks after the last dose of study treatment Written informed consent

Exclusion criteria

  • Metastatic or locally advanced (i.e. unresectable) pancreatic cancer.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PDL2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX40, CD137).
  • Has received prior systemic anti-cancer therapy including investigational agents for pancreatic cancer.
  • Has received prior radiotherapy within 2 weeks of start of study intervention.
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
  • Complete dihydropyrimidine dehydrogenase deficiency. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
  • Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (e.g, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid re placement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus infection.
  • Has had an allogenic tissue/solid organ transplant.
  • Serious concomitant systemic disorders that would compromise the safety of the patient or their ability to complete the study, at the discretion of the investigator.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
  • Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed.
  • A WOCBP who has a positive urine pregnancy test within 72 hours prior to start of treatment (see Appendix 6). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit until 18 weeks after the last dose of trial treatment.
  • Has contra-indications for MRI (only for Amsterdam UMC and RAKU)
  • Pacemakers or implanted defibrillators, deep brain stimulators, cochlear implants.
  • Patients who have a metallic foreign body in their eye, or who have an aneurysm clip in their brain, cannot have an MRI scan since the magnetic field may dislodge the metal.
  • Patients with severe claustrophobia not able to tolerate an MRI scan

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Neoadjuvant FOLFIRINOX, SABR and pembrolizumab
Treatment starts with four cycles of neoadjuvant modified FOLFIRINOX chemotherapy every two weeks, combined with pembrolizumab every six weeks, starting at the same day as the second cycle of mFOLFIRINOX. Restaging is performed after cycle 4 of mFOLFIRINOX with a CT-scan and tumor markers. Patients with a response or stable disease will undergo stereotactic radiotherapy 5 X 8 Gy followed by four additional cycles of mFOLFIRNOX and pembrolizumab every six weeks. Restaging is repeated after 8 cycles. Patients undergo surgical exploration, 3-6 weeks after completion of chemotherapy, if they have non-metastatic (borderline) resectable disease on CT-scan of the chest and abdomen. Patients also proceed to surgical exploration if they discontinue neoadjuvant mFOLFIRINOX and/or pembrolizumab because of toxicity or have locoregional progression at restaging. After surgery patients will start within 12 weeks with adjuvant 4 cycles of mFOLFIRINOX and 5 cycles of pembrolizumab every 6 weeks.
Drug: Pembrolizumab
Pembrolizumab 400 mg will be administered as a 30 minute IV infusion every 6 weeks.
Drug: Folfirinox
FOLFIRINOX is a combination of systemic chemotherapy agents. FOLFIRINOX consists of oxaliplatin at a dose of 85 mg/m2, given as a 2-hour intravenous infusion, immediately followed by leucovorin at a dose of 400 mg/m2 given as a 2-hour intravenous infusion, with the addition, after 30 minutes, of irinotecan at a dose of 150 mg/m2, given as a 90-minute intravenous infusion through a Y-connector. This treatment is followed by a continuous intravenous infusion of 2400 mg/m2 5-FU over a 46-hour period every 2 weeks. (The FOLFIRINOX given in the trial is the modified scheme, whereby the fluorouracil bolus at a dose of 400 mg/m2 is omitted and the irinotecan dose reduced to 150 mg/m2).
Radiation: SABR
SABR will be delivered in an image-guided hypofractionated scheme of 5 fractions of 8 Gy (total 40 Gy), prescribed to 95% of the planning target volume (PTV). Treatment is delivered on five non-consecutive days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
1-year progression-free survival rate
Time Frame: 12
12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Amsterdam UMC, location VUmc

Collaborators

Maastricht University Medical Center
Erasmus Medical Center
St. Antonius Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 23, 2024

Primary Completion (Estimated)

March 1, 2028

Study Completion (Estimated)

March 1, 2028

Study Registration Dates

First Submitted

April 16, 2024

First Submitted That Met QC Criteria

April 22, 2024

First Posted (Actual)

April 25, 2024

Study Record Updates

Last Update Posted (Actual)

February 13, 2026

Last Update Submitted That Met QC Criteria

February 10, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023-508707-20-00

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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