Unresectable Pancreatic Cancer

A unique approach for cancer treatment employing intratumoral diffusing alpha radiation emitter device for advanced pancreatic cancer

A unique approach for cancer treatment employing intratumoral diffusing alpha radiation emitter device for advanced pancreatic cancer

This is a single arm, open label, multi-center phase I study, including phase Ia dose escalation and phase Ib dose expansion. Safety review committee (SRC) will be formed to monitor safety and efficacy data through the study. And the independent review committee (IRC) will be formed to monitor efficacy data through the study.

This research study is being done to help determine the safety and efficacy of gadolinium based nanoparticle, Activation and Guidance of Irradiation X (AGuIX), used in conjunction with MR-guided stereotactic body radiation therapy (SBRT) in the treatment of pancreatic cancer and lung tumors.

The goal of this clinical trial is to learn if Autologous Drug-Loaded Neutrophils (NeuMed) can treat patients with Unresectable Pancreatic Cancer. The drug carried by the Autologous Neutrophils is Monomethyl Auristatin E. The main questions it aims to answer are: First, to verify the safety of Autologous Drug-Loaded Neutrophils (NeuMed) in patients with Unresectable Pancreatic Cancer. Second, to assess the anti-tumor efficacy of Autologous Drug-Loaded Neutrophils (NeuMed) in patients with Unresectable Pancreatic Cancer.

* Clinical trial phase: Phase 2 * Intervention model: Control group * Group allocation: Randomized controlled trial * Research perspective: Prospective study * Participating centers: Multicenter study * Definition of the intervention period: Based on the RECIST 1.1 guidelines, patients will receive treatment until dropout due to disease progression or unacceptable toxicity related to the trial drug. Patients will be followed up with to assess survival every 2 months until either death or the end of the trial, whichever is first. * The intervention period is from the date of IRB approval to December 31st, 2025 * The follow-up duration is one year, and the statistical analysis duration is six months * The total research period is from the date of IRB approval to June 30th, 2026

\- This will a be an open label, multicentre, randomized, controlled study in patients with unresectable pancreatic cancer, locally advanced or metastatic, with significant weight loss, and the tumour located in the head of the pancreas associated with dilated main pancreatic duct. Pancreatic Exocrine Replacement Therapy (PERT) in these patients will be given on top of other required therapies (best standard of care, BSC), including oncologic therapies, diabetes mellitus therapies and acid suppressants and nutritional support as appropriate. The duration of the study will be up to six months. Consecutive patients meeting inclusion criteria and none of the exclusion criteria will be evaluated for the study. Those patients signing the informed consent for study participation will be randomized to one of the following two arms: * The experimental arm will receive the best standard of care (BSC) and PERT (capsules containing pancreatin 35,000 Ph.U.) at a fixed dose of 3 capsules with main meals (breakfast, lunch and dinner) and 2 capsules with snacks over 6 months. * The control arm will receive the BSC over 3 months, followed by a further 3-month open uncontrolled phase of BSC + PERT at the dose mentioned above. All patients will receive in addition a proton pump inhibitor (PPI) bid (any PPI at standard dose is acceptable -omeprazole 20 mg, lansoprazole 30 mg, pantoprazole 40 mg, rabeprazole 20 mg, esomeprazole 40 mg) while on PERT, 20-30 minutes before breakfast and dinner. To make the two arms comparable, patients will be stratified in two groups (locally advanced and metastatic pancreatic cancer) for randomization using computer generated random numbers.