A study looking at the use of Mfolfirinox Chemotherapy And Stereotactic Radiotherapy for Patients with Locally Advanced pancreatic cancer to evaluate if this is a feasible treatment option with acceptable acute toxicity rates.

The intervention involved in this study are; - four cycles of mFOLFIRINOX chemotherapy (standard of care). This involves Oxaliplatin (75mg/m2) via intravenous administration, Irinotecan(150mg/m2) via intravenous administration, 5-fluorouracil (2400mg/m2) via continuous infusion over 4 days. This is done 4 times every 14 days. The chemotherapy is prescribed by a qualified medical oncologist and delivered by a qualified registered nurse. - insertion of fiducial markers used for imaging during radiotherapy which is performed more than 3 days before the commencement of SBRT. Fiducial markers that aid in the visualisation of the tumour during radiotherapy will be inserted prior to SBRT. The fiducial markers will be placed either percutaneously (needle puncture of the skin), intraoperatively (during surgery), or under Endoscopic ultrasound (EUS) guidance. The method used will depend on tumour location. This only needs to be performed at one time point. This will take approximately 30 minutes to complete. - SBRT will follow the completion of the four cycles of mFOLFIRINOX chemotherapy, SBRT will commence 2-4 weeks following the completion of mFOLFIRINOX chemotherapy based on clinician discretion. SBRT involves 5 treatments given over 2 to 3 weeks (depending on machine availability) to a dose of 30-45Gy. Patients are permitted to have treatment on two consecutive days but not three. Each SBRT treatment will take approximately 30 to 40 minutes each session. Dose per fraction will be 6 to 9Gy pending the location of the tumour. SBRT is prescribed by a qualified radiation oncologist and the SBRT is delivered by a qualified radiation therapist. - surgery (if cancer is resectable after chemotherapy and SBRT), - study blood tests. Study blood tests will be performed at baseline prior to chemotherapy, prior to cycle 2 , 3 and 4 of chemotherapy, prior to SBRT, 4 weeks following SBRT and at 3, 6, 12, 18 and 24 months following SBRT. These tests will require 35ml of blood to be taken (just over two tablespoons of blood). - Positron Emission Tomography (PET) imaging using 18F-MISO and 18FDG-PET (approximately 4 hours each), The PET scans (both the 18F-MISO and FDG-PET) involves the use of an intravenously administered radioactive drug (tracer) followed by the scan. The PET-CT scan will be performed by a suitably qualified allied health professional. The 18FDG-PET is performed at baseline as standard of care and the performed as a study procedure prior to SBRT and 4 weeks after completion of SBRT. The 18F-MISO PET is completed only as a study procedure at baseline, prior to SBRT and 4 weeks after completion of SBRT if available. - Magnetic Resonance Imaging (MRI). The MRI scans will be performed before and in the follow up stage after radiotherapy treatment over approximately a 24 month period. This includes MRI scans performed at least one week prior to radiotherapy treatment, and then 3, 6, 12, 18 and 24 months after radiotherapy treatment is finished. ALL MRI scans performed before or after the radiotherapy treatment are for the assessment of tumour and treatment response. The MRI scans will involve the use of a contrast agent administered intravenously by the treating doctor, unless contraindicated then no contrast will be used. The MRI scan will be performed by a suitably qualified allied health professional. - completion of quality of life (QoL) questionnaires. QoL questionnaires will be completed by the participant at baseline, prior to SBRT, 6 weeks after SBRT, 3 months after SBRT and 6 months after SBRT. Subsequently QOL will be completed 6 monthly up until and including the 18 month follow up appointment. The use of mFOLFIRINOX chemotherapy and SBRT in isolation has been tested but this study is testing the feasibility when they are combined. For the investigational PET imaging and MRI scans performed at baseline, prior to SBRT and 4 weeks following SBRT, these will be performed within a few days of each other at the same hospital but in different departments. All investigational blood tests will be performed on the same day as the routine clinic visit. The clinical trials team will document compliance of attendance at scheduled imaging. Patients who have not attended their scheduled imaging will be contacted by the clinical trials team and reasons for failure to attend will be sought. Where possible, attendance to reschedule appointments will be facilitated.