This study is a single-center, prospective, non-randomized trial. The population studied will consist of 10 patients of both sexes, aged 18 to 85 years, with a newly diagnosed metastatic pancreatic adenocarcinoma who will undergo palliative treatment with standard first line chemotherapy (Gemcitabine +/- Nab-paclitaxel). Diagnosis must be confirmed by biopsy and metastasis must be accessible for percutaneous biopsy using imaging guidance. Further, only patients with an IL-6 (GP130/STAT3)-pathway activity of more than 5% on diagnostic biopsy will be included .~In addition to chemotherapy, patients will receive 20 mg bazedoxifene (Conbriza®) orally per day, subject to good clinical tolerance and in the absence of a biological contraindication.~Patients will receive bazedoxifene once a day at any time, with or without meals. Initiation of treatment will be simultaneous to the initiation of chemotherapy. Bazedoxifene (Conbriza®) will be prescribed and administered for the duration of the study. To minimize the risk of thrombo-embolic events, prophylactic rivaroxaban (Xarelto®) 10 mg orally once per day will be added for the duration of the bazedoxifene (Conbriza®) intake. Pantoprazole 20 mg once per day will be added in selected patients to minimize gastric complications according to the physician's appreciation. Participants will receive bazedoxifene (Conbriza®) and rivaroxaban (Xarelto®) for the entire study duration from a subinvestigator at treatment initiation visit.~Physical examination with vital parameters, laboratory testing (blood count, liver enzymes, creatinine) and tumor marker (CA 19-9) will be conducted in order to determine the baseline prior to the initiation of the treatment. The quality of life using the EORTC core quality of life questionnaire (QLQ-C30) will also be assessed at that point. Furthermore, the IL-6 pathway activity (GP130/STAT3) will be assessed immunohistochemically on metastasis biopsy before administration of bazedoxifene (Conbriza®). The tissue will be obtained by percutaneous biopsy using imaging guidance. A biopsy performed before study inclusion can be used as baseline to avoid a second biopsy.~Study enrollment and follow-up will be performed by the consultant physician at the HFR Fribourg in the department of oncology. The follow-up will be carried out every 3 to 4 weeks and will consist of a physical examination, vital parameters, laboratory testing (blood count, liver enzymes, creatinine, electrolytes) and tumor marker (CA 19-9). Plasma samples will be collected before and after treatment for storage and samples will be analyzed through next generation sequencing NGS. Quality-of-life will be assessed during the follow-ups and drug adherence will be monitored through patient survey.~After 3 months of treatment, the primary endpoint will be assessed. Thoraco-abdominal CT scan or PET-CT will be performed, and a biopsy of metastasis tissue will be repeated (percutaneous under radiological guidance) for immunohistochemical IL-6 pathway activity (GP130/STAT3) analysis. The activity of bazedoxifene (Conbriza®) on inflammatory pathways and tumor progression will be evaluated by comparing the modification in expression of the IL-6 pathway (GP130/STAT3) from baseline.~Patients will be instructed by the investigator to report the occurrence of any adverse event.~The expected duration of the study for each participant will be 12 to 16 weeks.
Bazedoxifene, a selective estrogen receptor modulator is thought to have effective anti-tumoral properties for pancreatic cancer via IL-6 pathway (GP130/STAT3) inhibition.~The objective is to measure IL-6 (GP130/STAT3)-pathway modification on metastasis biopsy of patients with metastatic pancreatic adenocarcinoma before and after treatment with bazedoxifene in addition to chemotherapy.~This study is a single-center, prospective, nonrandomized trial.