Colon cancer MedDRA version: 20.0 Level: PT Classification code 10009944 Term: Colon cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: metformin
Pharmaceutical Form: Capsule
INN or Proposed INN: METFORMIN HYDROCHLORIDE
CAS Number: 1115-70-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number
Sponsors
Ismail Gögenur
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients with adenocarcinoma of the colon planned for elective curative intended surgery at Slagelse hospital - Age of 18 or above - Must be able to understand and sign informed content - Sufficient amount of representative tumor material from the biopsies taken at the initial colonoscopy must be present Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 33
Exclusion criteria
Exclusion criteria: - Patients diagnosed with diabetes mellitus - Patients who are receiving or have received metformin or other oral antidiabetics - Impaired kidney function (eGFR < 60mL/min) - Severe liver disease (defined as transaminases above X 3 normal levels) - Participation in another pharmacological intervention trial - Predictable poor compliance (for instance not speaking fluent Danish, mentally impaired) - Presenting with metastatic disease - Patients undergoing neoadjuvant chemotherapy - Pregnancy or lactation (fertile women must have a negative serum or urine pregnancy test to participate) - Fertile women who do not use safe contraception during the study period.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The aim of the study is to investigate the effect of treatment with metformin on cell proliferation and on metabolic and immunological changes in non-diabetic patients with colon cancer. The primary outcome is determination of the difference of the level of proliferation after the intervention (time of surgery) adjusted for the level seen at baseline (time of colonoscopy). Another primary outcome is the difference in tumorinfiltrating CD3 and CD8 positive lymphocytes after the intervention adjusted for the level seen at baseline.;Secondary Objective: Secondary outcomes: - The difference in the level of apoptosis after the intervention adjusted for levels seen at baseline. - the difference in proliferation, migration and adhesion of colon cancer cell lines treated with plasma from the patients. - Blood samples will be analyzed for metabolic and immunological changes. - analyses of up- and down regulation of relevant genes in blood and tumor samples using the NanoString technology. - postoperative hyperglycemia and insulin resistance will be measured by analyzing the difference in insulin resistance and plasma glucose levels before surgery and on postoperative day 1 and 2. - Postoperative complications within 30 days from surgery will be assessed and classified according to the Clavien-Dindo classification. - the effect of metformin on relevant pathways in enterocytes and hepatocytes respectively - the effect of metformin on bacterial microbiota in blood samples and biopsies of the gut;Primary end point(s): The primary outcome is determination of the difference of the level of proliferation (Ki67 expression) after the intervention (time of surgery) adjusted for the level seen at baseline (time of colonoscopy). Another primary outcome is the difference in tumor infiltration CD3 and CD8 positive lymphocytes after the intervention adjusted for the level seen at baseline;Timepoint(s) of evaluation of this end point: This will be evaluated at time of | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary outcomes: - The difference in the level of apoptosis after the intervention adjusted for levels seen at baseline. - The effect of metformin will be measured by examining the difference in proliferation, migration and adhesion of colon cancer cell lines treated with plasma from the patients. - Blood samples stored will be analyzed for metabolic and immunological changes. - Blood and tumor samples will be analyzed for differences in up- and down regulation of genes using the NanoString technology - The effect of metformin on postoperative hyperglycemia and insulin resistance will be measured by analyzing the difference in insulin resistance and plasma glucose levels before surgery and on postoperative day 1 and 2. - Postoperative complications within 30 days from surgery will be assessed and classified according to the Clavien-Dindo classification. - the effect of metformin on pathways in enterocytes and hepatocytes -the effect of metformin on the composition of the microbiota in blood samples and biopsies;Timepoint(s) of evaluation of this end point: Changes between baseline and at time of operation (before surgery either the same day as the operation or a couple of days before) will be measures as well as the levels on postoperative day 1,2 and 10. The effect of metformin on hyperglycemia and insulin resistance will be measured at time of surgery and on postoperative day 1 and 2. | — |
Countries
Denmark
Contacts
Public ContactDepartment of surgery
Department of surgery Slagelse Hospital
Outcome results
None listed