Inclusion Criteria:
* Patients with a histological diagnosis of PDAC. Those with unconfirmed histology must have this confirmed by EUS-FNB in the pre-screening period prior to commencement of chemotherapy. Invasive PDAC in the setting of intraductal papillary mucinous neoplasm (IPMN) is permitted.
* Patients must consent to EUS-FNB for correlative analysis even if adenocarcinoma has been confirmed, unless confirmation was performed using a previous biopsy or fine needle biopsy with adequate tumour tissue for GATA6 analysis.
* Resectable primary tumour on preoperative biphasic (arterial and venous phases) contrast-enhanced CT for pancreatic staging as per institutional standard of care, with ≤5 mm slice thickness. MRI for liver metastases (optional) as per institutional standard of care. The definition of resectability (as per NCCN guidelines - see Appendix B) includes:
* no involvement of the celiac artery, common hepatic artery or superior mesenteric artery (or if present a replaced right or common hepatic artery)
* no involvement or \<180 (interface between tumour and vessel wall, of the portal vein or superior mesenteric vein, and patent portal vein/splenic vein confluence\_
* For tumours of the body and tail of the pancreas, involvement of the splenic artery and vein of any degree is considered resectable disease
* Patients must be medically fit to undergo surgical resection
* No prior oncological treatment for index PDAC
* ECOG Performance status 0-1
* Age \> 18 years
* Patients must be medically suitable for treatment with mFFX as per treating medical oncologist
* No evidence of metastases (i.e., metastatic work-up negative including a CT scan of the chest, abdomen (IV and oral contrast, 3 phase) and pelvis)
* Adequate hematologic function
* absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
* platelets ≥ 100 000 cells/mm3
* hemoglobin ≥ 9 g/L (after transfusion is acceptable))
* Creatinine level \< 130 µmol/L or CrCl ≥ 50 ml/min
* Patients of child-bearing potential (for female patient: study entry after a menstrual period and a negative pregnancy test) must agree to use two medically acceptable methods of contraception (one for the patient and one for their partner) during the study and for 4 months after the last study treatment intake for women and 6 months for men. These patients must have a pregnancy test repeated every month while on chemotherapy.
* Patients must be able to provide written informed consent
* Adequate liver function (AST \<2.5 times the institutional upper limit of normal at the baseline visit, total bilirubin ≤ 2 times the institutional upper limit of normal at the baseline visit)
Exclusion Criteria:
* Patients where attempted EUS-FNB x 2 has not confirmed PDAC in the setting of unconfirmed histology.
* Patients in whom histology has confirmed PDAC but who do not consent to EUS-FNB, unless previous confirmation was by biopsy or fine needle biopsy with adequate tumour tissue for GATA6 analysis.
* Non-ductal pancreas tumours including endocrine tumours, acinar cell carcinoma, cyst adenocarcinoma or ampullary tumours.
* Unresectable PDAC by contrast enhanced CT or MRI. Borderline resectable PDAC (vein and artery) are excluded from this study
* Evidence of metastatic disease
* Prior treatment for index PDAC
* Previous autologous bone marrow transplant or stem cell rescue
* Active hepatitis B or C infection
* Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
* History of another primary cancer within the last 3 years with the exception of non-melanoma skin cancer, early stage prostate cancer or curatively treated cervical carcinoma in situ or other indolent malignancy (discretion of PI).
* Pregnant or breast-feeding patients are excluded from this study as the chemotherapy agents used in this study have been demonstrated or have the potential to be teratogenic and there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother
* Patients who are being therapeutically anticoagulated with coumadin and cannot have an alternative anticoagulation regimen.
* Known hypersensitivity to any of the drugs used or their components.
* Patients with known complete absence of dihydropyrimidine dehydrogenase (DPD) activity.
* History of QT prolongation or receiving QT prolonging medications.
* History of Gilberts condition
