Metformin hydrochloride for Esophageal adenocarcinoma

Inclusion criteria

• {"criterion_text":"- Surgical resectable (\n- Adult patients (age ≥ 18 years).\n- ECOG performance status 0 or 1 (cf. Appendix A).\n- Adequate hematological, renal and hepatic functions defined as: o\tAbsolute Neutrophil Count ≥ 1.5 x 109/L o\tplatelets ≥ 100 x 109/L o\thaemoglobin ≥ 5.6 mmol o\ttotal bilirubin ≤ 1.5 x upper normal limit o\tcreatinine clearance (Cockroft) > 30 ml/min\n- Patients must be willing to undergo two endoscopies for investigational purposes.\n- Written, voluntary informed consent\n- Patients must be accessible to follow up and management in the treatment center"}

Exclusion criteria

• {"criterion_text":"- Patients diagnosed with diabetes mellitus type 1 or 2 receiving anti-diabetic drugs.\n- Patients prescribed metformin or another anti-diabetic drug for any reason.\n- Patients allergic or intolerant to metformin.\n- Previous systemic therapy or radiotherapy on the oesophagus.\n- Severe renal impairment (CLcr ≤ 30 ml/min).\n- Past (within 5 years) or current history of malignancy other than entry diagnosis interfering with prognosis of esophageal cancer\n- Previous systemic therapy for other forms of cancer within the last six months.\n- Patients with prior allogeneic stem cell or solid organ transplantation\n- Pregnancy (positive serum pregnancy test), planning to become pregnant, and lactation.\n- Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) precluding major surgery.\n- Pulmonary fibrosis, active, non-infectious pneumonitis and/or severely impaired lung func-tion precluding major surgery and/or radiation.\n- Serious underlying medical condition which would impair the ability of the patient to re-ceive the planned treatment, including prior allergic reactions to drugs containing Cremo-phor, such as teniposide or cyclosporine.\n- Dementia or altered mental status that would prohibit the understanding and giving of in-formed consent"}

Primary endpoints

• {"endpoint_text":"- Metabolic switch in macrophages measured by M2 to M1 macrophage polarization within the tumour immune microenvironment and the number of CD8 intratumoral T-cell infiltration determined with single cell mRNA sequencing.","definition_or_measurement_approach":"Measured by M2 to M1 macrophage polarization within the tumour immune microenvironment and the number of CD8 intratumoral T-cell infiltration determined with single cell mRNA sequencing."}

Secondary endpoints

• {"endpoint_text":"- Measure changes in T cell infiltration and the CD3:CD163 ratio within the spatial context by multicolor immunohistochemistry (mIHC).","definition_or_measurement_approach":"Measured by multicolor immunohistochemistry (mIHC) to assess T cell infiltration and CD3:CD163 ratio in spatial context."}
• {"endpoint_text":"- Detect metabolic changes in macrophages and T cells in the tumour immune microenvi-ronment by SCENITH flow cytometry analysis.","definition_or_measurement_approach":"Detection of metabolic changes using SCENITH flow cytometry analysis on tumour immune microenvironment cells."}
• {"endpoint_text":"- Pathological response according to pTNM stage and Mandard criteria","definition_or_measurement_approach":"Pathological response assessed using pTNM staging and Mandard criteria."}
• {"endpoint_text":"- Adverse events based on Common Toxicity Criteria for Adverse Events (CTCAE).","definition_or_measurement_approach":"Adverse events graded and reported according to CTCAE criteria."}
• {"endpoint_text":"- Progression free survival","definition_or_measurement_approach":"Time-to-event measure: progression-free survival as defined by protocol (time from enrolment to disease progression or death)."}
• {"endpoint_text":"- Overall survival","definition_or_measurement_approach":"Time-to-event measure: overall survival (time from enrolment to death from any cause)."}

Netherlands

Earliest CTIS Part Ii Submission Date

19-07-2024

Latest Decision Or Authorization Date

21-10-2025

Processing Time Days

459

Number Of Sites

2

Number Of Participants

14

Primary sponsor

Full Name

Amsterdam UMC Stichting

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands