Effect of Metformin on Biomarkers of Colorectal Tumor Cell Growth

May 31, 2016 updated by: University of Arkansas

Pilot Study: Effect of Metformin on Biomarkers of Colorectal Tumor Cell Growth

The purpose of this study is to investigate the effects of short term oral Metformin therapy on biomarkers for tumor growth in subjects with newly diagnosed colon or rectal adenocarcinoma.

It is hypothesized that there are independent actions of Metformin on the outcome of subjects with colorectal cancer (CRC). Also hypothesized is that metformin effects on CRC cell growth will correlate with this drug's effects on markers mentioned above, because the markers are closely related to tumor growth and metastases.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

This is a randomized, double-blinded placebo controlled clinical investigation of the effects of short term oral Metformin therapy on biomarkers for tumor growth in subjects with newly diagnosed colon or rectal adenocarcinoma. Metformin is a well-tolerated drug widely prescribed for treatment of Type 2 diabetes mellitus. Preliminary studies have generated the hypothesis that metformin may have positive effects on both prevention and survival of colon cancer subjects. Clinical trials are ongoing to explore this possibility in breast cancer (NCT01101438). This investigation is the first study of Metformin in colorectal cancer (CRC) patients, and is designed to understand the mechanism of its anti-cancer actions, if any, and its interactions with biomarkers in colorectal cancer patients.

Based upon epidemiological studies, it is hypothesized that there are independent actions of Metformin on the outcome of subjects with CRC. Also hypothesized is that metformin effects on CRC cell growth will correlate with this drug's effects on markers mentioned above, because the markers are closely related to tumor growth and metastases.

Study Type

Interventional

Enrollment (Actual)

7

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas for Medical Sciences
      • Little Rock, Arkansas, United States, 72205
        • Central Arkansas Veterans Heathcare System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female, all races and ethnicities are eligible
  • Age equal to or greater than 18 years of age
  • All subjects should have a pathological/histological diagnosis of colorectal cancer.
  • Clinical diagnosis of stage I, II, III or IV colon cancer or stage I, II, III or IV rectal cancer; cancer may be primary including a secondary primary
  • Candidate for elective surgery(for removal of primary) or endoscopic biopsy
  • ECOG Performance status of 0 - 2
  • Adequate renal, liver, and bone marrow function
  • Hb: (adequate for surgical intervention, with transfusion if necessary)
  • WBC: (normal range)
  • Platelets: (180K/cmm)
  • LFTs: Normal bilirubin (< 2.0mg/dL), AST/ALT (2xULN)
  • Renal function: normal creatinine
  • Subjects must have signed informed consent
  • Female subjects must either not be of child-bearing potential or must have a negative urine pregnancy test within 7 days of beginning the drug or placebo treatment. Subjects are considered not of child-bearing potential if they are surgically sterile or they are postmenopausal for greater than 12 months.

Exclusion Criteria:

  • Previously diagnosed with diabetes mellitus Type 1 or Type 2.
  • Currently taking biguanides, sulfonylurea drugs, thiazolidinediones, insulin, or mTOR inhibitors or having taken any of these medications during the 12 weeks prior to study participation.
  • Currently taking any non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin and unable to stop such medications due to a present medical condition.
  • Clinical symptoms of gastrointestinal obstruction or bleeding and consideration for immediate surgery or immediate neoadjuvant chemoradiation.
  • Familial Adenomatous Polyposis (FAP), hereditary non-polyposis colorectal cancer (HNPCC), Putz-Jeghers disease, ulcerative colitis, or Crohn's disease.
  • Pregnant or lactating.
  • History of lactic or other metabolic acidosis.
  • Known hypersensitivity to Metformin.
  • Uncontrolled infectious disease.
  • History of Positivity for human immunodeficiency virus (HIV).
  • History of congestive heart failure requiring pharmacologic treatment.
  • History of excessive alcohol abuse, defined by a habitual intake of more than three drinks daily.
  • Previous or concurrent malignancies, except non-melanoma skin cancers, unless curatively treated and with no evidence of recurrence for > 5 years, with the exception of prior CRC which has been treated and the patient has been in remission and the current primary tumor is a second CRC.
  • Unable to swallow and retain oral medication.
  • Mal-absorption syndrome, disease affecting gastrointestinal function, or previous resection of the stomach or small bowel.
  • Current use of medications for weight loss.
  • Currently taking cimetidine, thiazide diuretics or cephalexin. If a patient needs some of these agents, alternative agents should be substituted.
  • If the physician feels that the candidate is not suitable for the study, he/she will be excluded.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Placebo 2 capsules by mouth twice daily; minimum of 10 days, maximum of 21 days
Drug: Placebo
2 capsules by mouth twice daily; minimum of 10 days, maximum of 21 days
Other Names:
  • inactive drug
Active Comparator: Metformin
Metformin 850 mg (2 capsules) by mouth twice daily; minimum of 10 days, maximum of 21 days
Drug: Metformin
850 mg (2 capsules) by mouth twice daily; minimum of 10 days, maximum of 21 days
Other Names:
  • Glucophage
  • Glucophage XR
  • Glumetza
  • Fortamet
  • Riomet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Proliferation Status of CRC Tumor and Adjacent Normal Tissue Following Metformin Therapy
Time Frame: 10-21 days
10-21 days
Mucosal Apoptotic Status of CRC Tumor and Adjacent Normal Tissue Following Metformin Therapy
Time Frame: 10-21 days
10-21 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Arkansas

Investigators

  • Principal Investigator: Rangaswamy Govindarajan, MD, University of Arkansas
  • Principal Investigator: Frank Simmen, PhD, University of Arkansas

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2012

Primary Completion (Actual)

January 1, 2015

Study Completion (Actual)

January 1, 2015

Study Registration Dates

First Submitted

June 27, 2012

First Submitted That Met QC Criteria

June 28, 2012

First Posted (Estimate)

June 29, 2012

Study Record Updates

Last Update Posted (Estimate)

July 11, 2016

Last Update Submitted That Met QC Criteria

May 31, 2016

Last Verified

May 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 134190

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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