Oesophageal AdenocarcinomaPhase 2MEMENTONCT06687876
Metformin as a Metabolic Intervention in Oesophageal Adenocarcinomas to Improve Response to Neoadjuvant Chemoradiotherapy
A Phase 2 study testing Metformin in people with Oesophageal Adenocarcinoma and Tumor Microenvironment, run by Amsterdam UMC, location VUmc at 2 sites in Netherlands.
Trial summary
The primary objective of this study is to investigate whether two weeks of metformin treatment can activate the tumour microenvironment in patients with stage II and III oesophageal adenocarcinomas. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Oesophageal Adenocarcinoma, Tumor Microenvironment
- What is being tested?
- Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 2 sitesNetherlands
- Study dates
- 9 Mar 2025to Dec 2030
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands2 sites, 2 recruiting
- Not yet recruiting
Amsterdam UMC
Amsterdam
Kayla Brugman, +3120 44 45869, c.brugman@amsterdamumc.nl
- Recruiting
Amsterdam UMC
Amsterdam
C.P. Brugman, MD, 02044445869, c.brugman@amsterdamumc.nl
About this study
Official title: Metformin as a Metabolic Intervention in Oesophageal Adenocarcinomas to Improve Response to Neoadjuvant Chemoradiotherapy.
The primary objective of this study is to investigate whether two weeks of metformin treatment can activate the tumour microenvironment in patients with stage II and III oesophageal adenocarcinomas.
Read the detailed description
Worldwide oesophageal adenocarcinoma (OAC) is one of the most deadly cancers. Even in case of non-metastatic disease, when patients are treated with neoadjuvant chemoradiotherapy (nCRT) and a surgical resection, around 50% of patients suffer from recurrent disease which is associated with a poor prognosis. While 23% of OACs have a complete histopathological response after nCRT, 18-35% lack any effect of nCRT. Previously, we have identified that a complete pathological response to nCRT is associated with an active tumour immune microenvironment (TIME) characterized by high intratumoral T cell levels and a higher CD3:CD163 ratio.
To improve response to nCRT we need to identify and target the mechanisms OACs use to suppress the TIME. Using spatial transcriptomics to identify differences between OACs with a T cell-dominant and a T cell-excluded microenvironment, we identified fatty acid oxidation (FAO) as central feature of T cell low OACs (unpublished data). This is an interesting observation as lipid metabolism is strongly associated with an immunosuppressive microenvironment. Metabolic re-programming by drugs such as metformin has shown to be a promising strategy to reactivate the anti-tumour immune response in other cancer types.
Over the past decade, metformin has been associated with a beneficial effect in cancer treatment as it has shown to decrease the risk of various cancer types in diabetic patients. More recent, metformin treatment has shown to increase the number of CD8+ tumour infiltrating lymphocytes by preventing apoptosis of these lymphocytes in cancers such as oesophageal squamous cell carcinomas. In addition, metformin can reduce M2-like macrophage polarization due to changes in cytokine expression in cancer cells and thereby stimulate a more pro-inflammatory TIME. In this study we want to investigate the effect of metformin on the TIME in patients with OACs using pre- and post-treatment tumour biopsies prior to nCRT.
- Conditions
- Oesophageal Adenocarcinoma, Tumor Microenvironment
- Being tested
- Metformin
- Keywords
- metabolic intervention, adenocarcinoma, oesophageal cancer, metformin, tumor microenvironment, neoadjuvant chemoradiotherapy
- Medical subject headings
- Adenocarcinoma Of Esophagus, Adenocarcinoma, Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called Glucient
Twice a day 500mg of metfomrin orally (1000mg/day) during a 2-week period.
| Study group | Role | What they receive |
|---|---|---|
| Metformin | Experimental | 1000 mg (twice a day 500 mg) metformin orally will be administered during a 2-week period. This is followed by the standard of care, which is neoadjuvant chemoradiotherapy, involving paclitaxel (50 mg/m2), carboplatin (AUC=2), and radiotherapy (23 x 1.8 Gy over five weeks) followed by surgical resection. Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
activation of the tumour immune microenvironment after two week metformin treatment.
Activation of the tumor immune microenvironment measured by M2 to M1 polarization, CD8 intratumoral T cell infiltration and an increase of CD3 to CD163 ratio when comparing tumor biopsies from before and after treatment.
Measured: at enrollment and at end of metformin treatment at 2 weeks.
Secondary outcomes (5)
Tolerability and toxicity of metformin
Adverse events based on Common Toxicity Criteria for Adverse Events
Measured: From starting treatment to end of treatment at 7 weeks.
Metabolic change of cancer cells with SCENITH analysis.
To determine whether SCENITH can be used to assay the change in metabolic state.
Measured: at enrollment and at end of metformin treatment at 2 weeks
Pathological response
According to the Mandard criteria.
Measured: After surgery, approximately 16 weeks after enrollment.
Progression-free survival (PFS).
Assess the PFS of patients within the study
Measured: 60 months
Overall survival (OS)
Determine overall survival of patients within the study
Measured: 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2024
- Study start9 Mar 2025
- Primary completionDec 2026 (estimated)
- Study completionDec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Oesophageal AdenocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Collaborators
- Cancer Center Amsterdam Research Foundation
- Responsible party
- Principal investigator, Sarah Derks, Amsterdam UMC, location VUmc
- Investigators
- Sarah Derks, MD PhD, Principal investigator, Amsterdam UMC, location VUmcHanneke W.M. van Laarhoven, MD, PhD, Principal investigator, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06687876
- Sponsor's protocol ID
- 2024.0935
- Other IDs
- 2024-511626-30-00
- Acronym
- MEMENTO
- Status last verified
- Jul 2025
- First submitted
- 5 Nov 2024
- Last updated
- 10 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: It is undecided.