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

Trial Title: Neoadjuvant Triple Treatment for Borderline Resectable Pancreatic Cancer (PREOPANC-5)

NCT ID: NCT06384560

Condition: Borderline Resectable Pancreatic Cancer

Conditions: Official terms:
Pancreatic Neoplasms
Pembrolizumab
Folfirinox

Conditions: Keywords:
borderline pancreatic cancer
neoadjuvant treatment
checkpoint inhibition
chemotherapy
stereotactic radiotherapy
surgical resection
progression free survival

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Pembrolizumab
Description: Pembrolizumab 400 mg will be administered as a 30 minute IV infusion every 6 weeks.
Arm group label: Neoadjuvant FOLFIRINOX, SABR and pembrolizumab

Intervention type: Drug
Intervention name: Folfirinox
Description: 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).
Arm group label: Neoadjuvant FOLFIRINOX, SABR and pembrolizumab

Intervention type: Radiation
Intervention name: SABR
Description: 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.
Arm group label: Neoadjuvant FOLFIRINOX, SABR and pembrolizumab

Summary: Since patients with borderline resectable pancreatic cancer (BRPC) 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 chemotherapy, immunotherapy and radiotherapy, followed by surgery and chemotherapy and immunotherapy survival in patients with BRPC.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - 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 Exclusion Criteria: - 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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Start date: July 2024

Completion date: March 2028

Lead sponsor:
Agency: Amsterdam UMC, location VUmc
Agency class: Other

Collaborator:
Agency: Maastricht University Medical Center
Agency class: Other

Collaborator:
Agency: Erasmus Medical Center
Agency class: Other

Collaborator:
Agency: St. Antonius Hospital
Agency class: Other

Source: Amsterdam UMC, location VUmc

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06384560