Metformin as a Metabolic Intervention in Oesophageal Adenocarcinomas to Improve Response to Neoadjuvant Chemoradiotherapy

Inclusion Criteria: * Surgical resectable (\<T4b, N0 or N+, M0), and histologically proven adenocarcinoma of the oesophagus or gastro-oesophageal junction planning to undergo neoadjuvant chemoradiotherapy. * Adult patients (age ≥ 18 years). * ECOG performance status 0 or 1 (cf. Appendix A). * Adequate hematological, renal and hepatic functions defined as: * Absolute Neutrophil Count ≥ 1.5 x 10\^9/L * Platelets ≥ 100 x 10\^9/L * Hemoglobin ≥ 5.6 mmol * Total bilirubin ≤ 1.5 x upper normal limit * Creatinine clearance (Cockroft) \> 30 ml/min * Patients must be willing to undergo two endoscopies for investigational purposes. * Written, voluntary informed consent. * Patients must be accessible to follow up and management in the treatment center. Exclusion Criteria: * Patients diagnosed with diabetes mellitus type 1 or 2 receiving anti-diabetic drugs. * Patients prescribed metformin or another anti-diabetic drug for any reason. * Patients allergic or intolerant to metformin. * Excessive alcohol consumption. * Use of OCT1/OCT2 inhibitors (e.g. verapamil, cimetidine, dolutegravir, isavuonazol, trimethoprim, vandetanib, crizotinib and Olaparib). * Use of OCT1/OCT2 inducers (e.g. rifampicine). * Use of immunosuppressive medication (corticosteroids, cyclosporine, tacrolimus, sirolimus, everolimus, cyclophosphamide). * Previous systemic therapy or radiotherapy on the oesophagus. * Severe renal impairment (CLcr ≤ 30 ml/min). * Past (within 5 years) or current history of malignancy other than entry diagnosis interfering with prognosis of oesophageal cancer. * Previous systemic therapy for other forms of cancer within the last six months. * Patients with prior allogeneic stem cell or solid organ transplantation * Pregnancy (positive serum pregnancy test), planning to become pregnant, and lactation. * Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) precluding major surgery. * Pulmonary fibrosis, active, non-infectious pneumonitis and/or severely impaired lung function precluding major surgery and/or radiation. * Serious underlying medical condition which would impair the ability of the patient to receive the planned treatment, including prior allergic reactions to drugs containing Cremophor, such as teniposide or cyclosporine. * Dementia or altered mental status that would prohibit the understanding and giving of informed consent.