Metformin as a Metabolic Intervention in Oesophageal Adenocarcinomas to Improve Response to Neoadjuvant Chemoradiotherapy
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorAmsterdam UMC, location VUmc
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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).
Absolute Neutrophil Count ≥ 1.5 x 10^9/L
Disqualifiers
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.
Trial design
Design model
Single group
Treatments tested in this trial
Metformin
DrugTwice a day 500mg of metfomrin orally (1000mg/day) during a 2-week period.
Treatment groups
14 Participants
are divided into 1 treatment groupGroup A: MetforminExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
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.
Time frame
at enrollment and at end of metformin treatment at 2 weeks.Secondary outcomes
1
Tolerability and toxicity of metformin
Adverse events based on Common Toxicity Criteria for Adverse Events
Time frame
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.
Time frame
at enrollment and at end of metformin treatment at 2 weeks3
Pathological response
According to the Mandard criteria.
Time frame
After surgery, approximately 16 weeks after enrollment.4
Progression-free survival (PFS).
Assess the PFS of patients within the study
Time frame
60 monthsOther outcomes
1
Can metformin induce a metabolic switch in macrophages, T cells and cancer cells.
Using single cell RNA sequencing or SCENITH analysis.
Time frame
20 months2
Change in subgroups in peripheral blood mononuclear cells (PMBCs) after metformin treatment.
Are the changes to the tumour immune microenvironment also detected in subgroups of peripheral blood mononuclear cells (PBMCs) taken at the same time points.
Time frame
20 months3
Establish immune cell co-cultures with primary tumour cells and investigate the cell interactions and anti-tumour responses in presence of metformin.
Establish autologous immune cell co-cultures with primary tumor cells to investigate immune cell-tumor cell interactions and anti-tumour responses in the presence of metformin.
Time frame
20 months4
Cytokine release profile measured in serum before and after metformin treatment.
Determine changes in cytokine expression in serum before and after metformin treatment.
Time frame
20 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Amsterdam UMC, location VUmc
Lead sponsor
Cancer Center Amsterdam Research Foundation
Collaborator
Source ClinicalTrials.gov