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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.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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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
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
Are there results?
Not yet: the study is under way

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.

Kayla Brugman, Master of Medicine contact

+3120 44 45869

c.brugman@amsterdamumc.nl

Netherlands2 sites, 2 recruiting

  • Amsterdam UMC

    Amsterdam

    Kayla Brugman, +3120 44 45869, c.brugman@amsterdamumc.nl

    Not yet recruiting

  • Amsterdam UMC

    Amsterdam

    C.P. Brugman, MD, 02044445869, c.brugman@amsterdamumc.nl

    Recruiting

Other trials in Netherlands

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.

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 groups in NCT06687876
Study groupRoleWhat they receive
MetforminExperimental1000 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.

  1. 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)

  1. 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.

  2. 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

  3. Pathological response

    According to the Mandard criteria.

    Measured: After surgery, approximately 16 weeks after enrollment.

  4. Progression-free survival (PFS).

    Assess the PFS of patients within the study

    Measured: 60 months

  5. 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.

  1. First posted14 Nov 2024
  2. Study start9 Mar 2025
  3. Primary completionDec 2026 (estimated)
  4. Study completionDec 2030 (estimated)

Resources

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)
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.

Questions about this trial

What is this clinical trial studying?

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.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 10 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Kayla Brugman, Master of Medicine (+3120 44 45869, c.brugman@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

activation of the tumour immune microenvironment after two week metformin treatment. (time frame: at enrollment and at end of metformin treatment at 2 weeks.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06687876.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2025.

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