Preoperative mFOLFIRINOX (or Gem-Nab-P) +/- Isotoxic High-dose SBRT for Borderline Resectable Pancreatic Adenocarcinoma (STEREOPAC)

This is an interventional treatment trial for Pancreatic Neoplasm focused on measuring borderline resectable pancreatic cancer, neoadjuvant therapy, stereotactic body radiation therapy, chemotherapy Read More

Inclusion Criteria:

• Cytologic or histologic proof of adenocarcinoma of the pancreatic head or uncinated process or body. Diagnosis should be verified by local pathologist
• cTNM stage: T1-4N0-2M0
• Confirmation of clinical and radiographic stage as borderline or at risk resectable* determined centrally by review of a diagnostic multisliced triphasic CT scan and/or MRI scan with contrast by a multidisciplinary board, composed by a dedicated oncological surgeon, radiologist and GI oncologist
• Age > 18 years old
• No prior chemotherapy or radiation for pancreatic cancer unless the neoadjuvant regimen as described
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• No grade ≥ 2 neuropathy
• Laboratory parameters as follows:
• Absolute neutrophil count (ANC) ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL
• Creatinine ≤ 1.5 x upper limit of normal (ULN) or estimated GFR > 45 mL/min
• Bilirubin ≤ 1.5 x ULN, including after adequate biliary stenting with metal stent (ideally 4 cm length)
• Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 2.5x ULN

• CA 19.9 < 2500 kU/l (baseline and absence of cholestasis)

  • High-risk features for resectable disease as defined by NCCN (version 2.2021) and ASCO criteria, including: any vascular encasement, elevated CA 19.9, poor (nutritional) condition, large tumor (> 4cm) and/or involved loco-regional LN at CT, MRI or PET.

Exclusion Criteria:

• Evidence of extrapancreatic disease on diagnostic imaging (CT, MRI or PET scan), histologically proven or at laparoscopy, including distal nodal involvement beyond the peripancreatic tissues (including non-regional lymph node involvement, ie: proven involvement of precaval lumbar lymphadenopathy(ies) and/or distant metastases
• Locally advanced disease as defined by the NCCN criteria (version 2.2021) ie > 180° arterial encasement (SMA and CA) unreconstructible venous encasement (SMV/PV) due to tumor involvement or occlusion of a long segment.
• CA 19.9 > 2500 kU/l (baseline and absence of cholestasis)
• Contraindication of surgery (general)
• Contraindications to receive FFX or gemcitabine-nab-Paclitaxel
• History of radiotherapy of the upper abdomen
• Prior treatment with oxaliplatin, irinotecan, fluoruouracil or capecitabin
• Patient < 18 years old
• Major surgery within 4 weeks of study entry
• Uncontrolled pre-existing disease including, but not limited to: active infection, symptomatic congestive heart failure, unstable angina, social / psychiatric disorder that would limit compliance to treatment and good understanding of the informed consent form
• Other concurrent anticancer therapies
• Existence of another active neoplasia other than basal cell carcinoma of the skin, cervical carcinoma in situ or non-metastatic prostate cancer. Patients who have a history of neoplasia must have been in remission for more than 5 years to be included in the protocol
• Pregnant or breastfeeding women; for women of childbearing potential only, a negative pregnancy test done < 7 days prior to registration is required. Using of reliable contraception for at least 1 month before treatment is mandatory
• Chronic concomitant treatment with strong inhibitors of cytochrome p450, family 3, subfamily a, polypeptide 4 gene (CYP3A4) is not allowed on this study; patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study

Additional exclusion criteria before randomisation:

• Progressive disease (RECIST or PETCT, including non locoregional nodal involvement and increase of CA 19.9 by 20%) after receiving 4 cycles of FFX (or G/NP), including shift chemotherapy in case of early progression.
• Presence of unmanageable toxicity during the first part of neoadjuvant chemotherapy (first 4 cycles or 6 doses of FFX or G/NP, respectively.
• Pancreatic tumour > 6.0 cm in greatest axial dimension at the time of randomization
• Massive invasion of the stomach or intestines and/or direct intestinal invasion of the mucosae visible at ultrasoundendoscopy
• Active gastric or duodenal ulcer disease at the time of randomization. Tolerated in case of antecedent without active ulcer (confirmation by endoscopy before SBRT)