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

NCT06384560 | Recruiting Phase 1 DMC

• 1 other identifier: 2023-508707-20-00
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Localized Pancreatic Adenocarcinoma; Borderline Resectable Pancreatic Adenocarcinoma; Resectable Pancreatic Adenocarcinoma

Keywords

neoadjuvant treatment; checkpoint inhibition; chemotherapy; stereotactic radiotherapy; surgical resection; progression free survival; resectable pancreatic cancer; localized pancreatic cancer; borderline resectable pancreatic cancer; FOLFIRINOX; pembrolizumab

Outcome Measures

Primary Outcomes (1)

• 1-year progression-free survival rate

  12

Study Arms (1)

Neoadjuvant FOLFIRINOX, SABR and pembrolizumab

EXPERIMENTAL

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; Drug: Folfirinox; Radiation: SABR

Interventions

Pembrolizumab DRUG

Pembrolizumab 400 mg will be administered as a 30 minute IV infusion every 6 weeks.

Neoadjuvant FOLFIRINOX, SABR and pembrolizumab

Folfirinox DRUG

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).

Neoadjuvant FOLFIRINOX, SABR and pembrolizumab

SABR RADIATION

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.

Neoadjuvant FOLFIRINOX, SABR and pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead
• Maastricht University Medical Center: collaborator
• Erasmus Medical Center: collaborator
• St. Antonius Hospital: collaborator

Study Sites (4)

Amsterdam University Medical Center

Amsterdam, Netherlands

RECRUITING

Maastricht University Medical Center

Maastricht, Netherlands

NOT YET RECRUITING

St. Antonius Ziekenhuis

Nieuwegein, Netherlands

RECRUITING

Erasmus University Medical Center

Rotterdam, Netherlands

RECRUITING

MeSH Terms

Interventions

pembrolizumab; folfirinox

Central Study Contacts

J. W. Wilmink, MD, PhD

CONTACT

+31 204444321; j.w.wilmink@amsterdamumc.nl

A. M. Gehrels, MD, MA

CONTACT

a.gehrels@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr.

Study Record Dates

• First Submitted: April 16, 2024
• First Posted: April 25, 2024
• Study Start: September 23, 2024
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028
• Last Updated: February 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

NL (4)