Metformin Treatment for Colon Cancer

NCT03359681 | Completed Phase 2 DMC

• 1 other identifier: REG-096-2017
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This is a double-blinded placebo controlled randomized trial examining the effect of metformin in non-diabetic patients with colon cancer on cell growth, immunological and metabolic changes. Patients are randomized to receive metformin 20 days before and 10 days after surgery. Tumor samples are examined for changes in level of cell growth and the composition of tumor cells in the tumor is examined. Blood samples are assessed for immunological markers and insulin resistance is measured. Cell proliferation, migration and adhesion are also examined in vitro by adding plasma obtained from the patients to colon cancer cell lines grown in culture.

Conditions

Colon Cancer

Outcome Measures

Primary Outcomes (1)

• Expression of Ki67 on tumor samples

  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). This is done using immunohistochemical staining for Ki67 (a marker for proliferation) of biopsies from the tumor. The level of proliferation will be defined as the percentage of tumor nuclei showing Ki67 staining in a specific microscopic field counted at the invasive front.

  colonoscopy (baseline) and at time of operation (after intervention)

Secondary Outcomes (10)

• Expression of cleaved Caspase-3 on tumor samples

  colonoscopy (baseline) and at time of operation (after intervention)

• immunoscore

  time of operation (after the tumor is removed)

• immunological changes in bloodsamples

  At baseline, day of operation and postoperative day 1, 2 and 10.

• insulin resistance

  At the day of surgery and postoperative day 1 and 2.

• blood glucose level

  4 times a day on postoperative day 1 and 2

Study Arms (2)

metformin hydrochloride

ACTIVE COMPARATOR

metformin, encapsulated tablet, 500mg 3 times a day for 30 days.

Drug: Metformin Hydrochloride

placebo oral capsule

PLACEBO COMPARATOR

placebo, encapsulated tablet, 500mg 3 times a day for 30 days.

Drug: Placebo oral capsule

Interventions

Metformin Hydrochloride DRUG

metformin 500mg three times a day 20 days before colon cancer surgery and 10 days after.

Also known as: metformin

metformin hydrochloride

Placebo oral capsule DRUG

placebo 500mg three times a day 20 days before colon cancer surgery and 10 days after.

Also known as: placebo

placebo oral capsule

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• Allergy to metformin or placebo

Sponsors & Collaborators

• Zealand University Hospital: lead

Study Sites (1)

Department of Surgery, Slagelse Hospital

Slagelse, 4200, Denmark

Location

Related Publications (1)

• Colov Tauby EP, Bojesen RD, Grube C, Miedzianogora REG, Buzquurz F, Fransgaard T, Knop FK, Gogenur I. Perioperative Metformin Treatment to Reduce Postoperative Hyperglycemia After Colon Cancer Surgery: A Randomized Clinical Trial. Dis Colon Rectum. 2024 Nov 1;67(11):1403-1412. doi: 10.1097/DCR.0000000000003426. Epub 2024 Jul 31.

  PMID: 39437217 DERIVED

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Metformin

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Emilie P Colov, MD

  Department of Surgery, Slagelse Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2017
• First Posted: December 2, 2017
• Study Start: July 10, 2018
• Primary Completion: September 2, 2021
• Study Completion: October 4, 2021
• Last Updated: March 3, 2022

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)