Prevention of Postoperative Pancreatic Fistula Following Pancreaticoduodenectomy by Preoperative Radiotherapy : a Phase 2 Trial

Prevention of Postoperative Pancreatic Fistula Following Pancreaticoduodenectomy by Preoperative Radiotherapy: a Phase 2 Trial

Design of the study Prospective, single arm, multicentric, phase II open trial Number of participating sites 14 French centers of HPB Surgery departments associated with 14 Radiation Oncology Departments.

Implementation of the study A screening of eligible patients will be made locally by the referring surgeon of each centre based on patient medical records.

• Inclusion visit at the first surgical consultation (W-3 to D1) (V0) The inclusion visit will be done by the surgeon within 3 weeks before the first radiation oncologist visit
• D1 (V1): first radiation oncologist visit
• W2 (+/- 3D) and W4 (+/- 3D) (V2 et V3): Preoperative simulation process and treatment delivery
• A first visit at W+2 (+/- 3 D) will be mandatory to validate the positioning of the target volume by CBCT with IV constrast or MRI
• Then to start of the administration of radiotherapy at W+4 (+/- 3 D): Radiotherapy with 20 Gy, in 2 fraction of 10Gy with a one-day gap, so over a total period of 3

W9 ( +/- 1W) (V4): post-radiotherapy follow-up

- Preoperative visit Day-1 before PD (V5)

W10 (+/- 1W) (V6):

• Pancreaticoduodenectomy and post operative hospitalisation W14 (+/- 1W) (V7): follow up with surgeon (30 days after pancreaticoduodenectomy)
• W22 (+/-1W) (V8): follow up with surgeon (90 days after pancreaticoduodenectomy)
• W34 (+/-1W) (V9): Last study visit (radiation oncologist) (6 months after pancreaticoduodenectomy) Medical follow-up by radiation oncologist at 6 months after surgery to assess the occurrence of potential late toxicities due to radiotherapy

Inclusion Criteria:

• Aged ≥ 45 years old
• Candidate for pancreaticoduodenectomy by laparotomy
• Body mass index (BMI) ≥ 25kg/m2
• Diameter of main pancreatic duct (MPD) < 3 mm on preoperative CT scan or MRI at the isthmus of the pancreas (future pancreatic section area)
• Affiliation to a social security system (AME excepted)
• Signed informed consent

Exclusion Criteria:

• Surgery indication : Chronic pancreatitis
• Surgery indication : Pancreatic ductal adenocarcinoma
• History of syndromic or hereditary pancreatic tumor
• Contraindication to pancreaticoduodenectomy
• Planned multivisceral resection involving organs or parts of organs not normally involved in pancreatico-duodenectomy
• Planned external drainage of the main pancreatic duct at the end of the surgery
• Neoadjuvant treatment planned or performed by chemotherapy or radiotherapy
• History of chronic hepatitis (F3) or cirrhosis (F4)
• Contraindication to radiotherapy
• Previous history of abdominal radiotherapy
• Extended pancreatic resection on the left beyond the radiotherapy area (left of the pancreatic isthmus)
• History of complicated peptic ulcer
• Patient treated for less than 4 weeks for an ulcer
• History of pancreatic surgery
• Ongoing pregnancy (confirmed by a test beta-HCG) or breast feeding or absence of birth control
• Patients with a active pathology or history that may interfere with the study in progress or the interpretation of its results according to the investigator
• Patients with a history or suspicion of non-compliance with medical regimens or will be unable to complete the entire study
• Treatment with systemic corticosteroids (excluding inhaled corticosteroids)
• Participation in another interventional clinical study (RIPH1, clinical investigation or clinical trial) or exclusion period set after the study
• Protected persons under legal guardianship or conservatorship