Phase 1 faecal microbiota transplantation in patients with advanced pancreatic carcinoma (FMTPanc Trial).

TPS4262 Background: Higher abundance of specific oral, pancreatic and/or gut microbes is correlated with pancreatic cancer occurrence (e.g. Porphyromonaas gingivalis , Malassezia sp.). Furthermore, the pancreatic tumour microenvironment of long-term survivors (≥ 5 years) shows richer tumoral microbial diversity associated with more active T-cells and fewer immune-suppressing cells than short-term survivors. Preclinical animal studies have also demonstrated that faecal microbiota transplantation (FMT) from a healthy donor or a long-term survivor can significantly decrease the size of pancreatic tumours. These findings demonstrate that manipulations of the gut and/or organ microbiota holds promise as part of cancer treatment. This trial aims to evaluate whether restoring a healthier microbiota can improve symptoms, visceral pain and treatment efficacy in people with non-resectable pancreatic cancer. Methods: This study is a Phase 1 double-blind randomised placebo-controlled trial (RCT) assessing the safety and potential benefit of oral FMT in patients with non-resectable pancreatic cancer. FMT will be a co-treatment to the standard of care chemotherapy. The primary outcomes are FMT safety and toxicity and mortality at 3, 6, and 12 months after chemotherapy initiation. Secondary outcomes include: changes in visceral pain and symptoms measured by PAGI-SYM, changes from baseline in blood CA-19-9 levels and reduction in tumour size as surrogate marker of treatment efficacy, and changes in faecal microbiota as a surrogate marker of gut flora restoration and treatment efficacy at 3, 6, and 12 months after treatment initiation. Power calculations were conducted for the main secondary clinical outcome of interest (i.e. the PAGI-SYM tool) that encompasses pain and symptom monitoring using published evidence, an MCID of 0.94, for an alpha of 0.05 and 80% power a minimum of 14 participants per arm is required. The trial aims to recruit a minimum of 28 and maximum of 60participants, 14-30 per arm. Eligible patients will have advanced and unresectable adenocarcinoma of the pancreas suitable for standard chemotherapy (gemcitabine/nab-paclitaxel or FOLFIRINOX) and be treatment-naive. Patients will be randomised 1:1 to FMT or placebo. FMT and placebo capsules will be prepared by BiomeBank (Adelaide South Australia). Stool will be sourced from healthy donors and rigorously screened following criteria specified by the Australian Therapeutic Administration (TGA). FMT/placebo will be provided through two doses (dose 1: 25mg, dose 2: 50mg). Chemotherapy will commence 3 to 14 days after completion of the first FMT dose (week 0). Supportive medication includes pancrelipase (2x25,000U three times a day) to facilitate digestion during FMT treatment. The FMTPanc is open at 3 sites across South Australia and Victoria and as of January 2025 12 patients have been enrolled. Clinical trial information: ANZCTR: ACTRN12624000455561.