Neoadjuvant Triple Treatment For Borderline Resectable Pancreatic Cancer (PREOPANC-5)

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 Plan

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

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2024-04-16	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-01-16
First Submitted that Met QC Criteria 2024-04-22	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-01-20
First Posted (ACTUAL) 2024-04-25	Results First Posted N/A	Last Verified 2025-01

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Neoadjuvant FOLFIRINOX, SABR and pembrolizumab Treatment starts with four cycles of neoadjuvant FOLFIRINOX chemotherapy every two weeks, combined with pembrolizumab every six weeks, starting at the same day as the second cycle of FOLFIRINOX. Restaging is performed after cycle 4 of FOLFIRINOX with a CT	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 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.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Neoadjuvant FOLFIRINOX, SABR and pembrolizumab

Treatment starts with four cycles of neoadjuvant FOLFIRINOX chemotherapy every two weeks, combined with pembrolizumab every six weeks, starting at the same day as the second cycle of FOLFIRINOX. Restaging is performed after cycle 4 of FOLFIRINOX with a CT

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

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.

Primary Outcome Measures	Measure Description	Time Frame
Percentage of patients with progression free survival at 18 months (RECIST 1.1)		18 months

Secondary Outcome Measures	Measure Description	Time Frame

Contacts and Locations

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

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.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Histologically or cytologically confirmed pancreatic cancer
Male or female participants who are at least 18 years of age on the day of signing in-formed consent
Borderline resectable tumor (see table 1 for definitions of resectability)
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Ability to undergo surgery, radiotherapy and chemotherapy
Leucocytes (WBC) ≥ 3.0 X 109/l
Platelets ≥ 100X 109 /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 5 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 5), not breastfeeding, or a woman of childbearing potential (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

Metastatic or locally advanced (i.e. unresectable) pancreatic cancer.
Ampullary or distal bile duct cancer.
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.
Complete dihydropyrimidine dehydrogenase deficiency.
A WOCBP who has a positive urine pregnancy test within 72 hours prior to start of treatment / (see Appendix 5). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
Has received prior therapy with an anti-PD-1, anti-PD-L1, or antiPDL2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, 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.
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 (eg, FluMist®) are live attenuated vaccines and are not allowed. COVID vaccines are allowed.
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.
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid thera-py (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 treat-ment within the past 2 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded
Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement 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 cur-rent pneumonitis.
Has an active infection requiring systemic therapy.
Has a known history of Human Immunodeficiency Virus (HIV) infection.
Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus infection.
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 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 through 120 days after the last dose of trial treatment.
Has had an allogenic tissue/solid organ transplant.
Has contra-indications for MRI (only for Amsterdam UMC and UMC Utrecht)

Pacemakers or implanted defibrillators, deep brain stimulators, cochlear im-plants.
Patients who have a metallic foreign body in their eye, or who have an aneu-rysm 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

Collaborators and Investigators

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

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Resources

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Caregivers

Clinical Trial Record