Metformin before pre-surgery chemoradiotherapy to boost immune activity in oesophageal adenocarcinoma

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This Phase 2, interventional trial gives eligible patients two weeks of metformin prior to standard neoadjuvant chemoradiotherapy and collects tumour biopsies by endoscopy to compare the tumour immune microenvironment before and after treatment. The study focuses on markers of immune activation such as intratumoral T cell levels and the CD3:CD163 ratio and explores fatty acid oxidation (FAO)–related changes that may suppress immune responses. Patients must be surgical candidates with resectable stage II–III oesophageal or gastro-oesophageal junction adenocarcinoma, have ECOG 0–1, and adequate organ function, and must not be taking anti‑diabetic drugs. Primary analyses will use tissue and molecular profiling to determine whether short-term metformin shifts the tumour microenvironment toward a more T cell–active state.

Why it matters

Who can join: the full rules

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.

Where it's running

• Amsterdam UMC
  Amsterdam, Netherlands Recruiting
• Amsterdam UMC
  Amsterdam, Netherlands Not yet recruiting

Study contacts

• Principal investigator: Sarah Derks, MD PhD — Amsterdam UMC, location VUmc
• Study coordinator: Kayla Brugman, Master of Medicine
• Email: c.brugman@amsterdamumc.nl
• Phone: +3120 44 45869

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.