Intra-Arterial Isolation Chemotherapy for Locally Advanced Unresectable Pancreatic Cancer

The treatment proposed in this clinical investigation plan is to repeatedly administer intra-arterial isolation chemotherapy to locally advanced pancreatic adenocarcinoma when the blood flow to and from the pancreas has been isolated via balloon catheters and positive end-expiratory pressure (PEEP). The objective of this study is to evaluate the tumour response, rates of conversion to resectability, 12-month survival, progression-free survival, quality of life, and treatment morbidity and mortality of repeated and isolated intra-arterial hepatic infusion of gemcitabine + oxaliplatin compared with the gold standards of intravenous gemcitabine, gemcitabine + nab-paclitaxel, and 5-FU/leucovorin/oxaliplatin/irinotecan (FOLFIRINOX) treatment. The treatment proposed in this study is based on the hypothesis that direct arterial infusion of chemotherapy to tumours in the pancreas whilst the blood flow to the organ is isolated could potentially yield benefits that cannot be achieved with existing treatment regimens. There are three treatment stages; implantation of a vascular access device (known as the AVAS), intra-arterial chemotherapy infusions, and explantation of the AVAS. IMPLANTATION: the participant is admitted to hospital and the AVAS is surgically implanted under general anaesthetic. The AVAS is an implantable large bore cannula with one end that can be anastomosed directly onto a peripheral vessel and the opposite end exiting the patient’s skin. The device can be opened to access the patient’s vasculature when required and closed when the device is not in use. In accordance with the manufacturer’s Instructions-For-Use (IFU), the AVAS will be implanted in the axillary artery (i.e. the upper pectoral area) or in the common femoral artery (upper thigh) by a trained vascular surgeon. The implantation procedure takes around 2 hours. After implantation, the participant is monitored overnight. INTRA-ARTERIAL CHEMOTHERAPY INFUSIONS: the participant is admitted to the angiography suite and under general anaesthetic or conscious sedation, intra-arterial pancreatic isolation chemotherapy infusion is administered by an interventional radiologist. Patients receive up to 12 infusions over an up to 8-week period. The first infusion can be administered 2 days after device implantation, and infusions are spaced such that there are no more than 2 infusions for 10 consecutive day period. Each infusion can take between 2-3 hours during the first few infusions but procedure times shorten (typically down to 1-2 hours as the radiologist becomes familiarised with the patient’s individual vascular anatomy. During the Phase Ib stage, gemcitabine + oxaliplatin will be administered with inter-patient escalation according to the accelerated titration model of dose escalation studies to determine a recommended phase 2 dose (RP2D). The RP2D will be used for all patients enrolled during the Phase II stage. EXPLANTATION: Device explantation may be performed immediately following the final infusion, or in a separate procedure at a later time depending on the availability of operating rooms and the condition of the participant. The surgical removal of the device takes approximately 1-2 hours, the participant is monitored overnight and discharged the next day.