Effect of Metformin on Biomarkers of Colorectal Tumor Cell Growth

NCT ID: NCT01632020

Last Updated: 2016-07-11

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

7 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-08-31

Study Completion Date

2015-01-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Colorectal Neoplasms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo

Placebo 2 capsules by mouth twice daily; minimum of 10 days, maximum of 21 days

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

2 capsules by mouth twice daily; minimum of 10 days, maximum of 21 days

Metformin

Metformin 850 mg (2 capsules) by mouth twice daily; minimum of 10 days, maximum of 21 days

Group Type ACTIVE_COMPARATOR

Metformin

Intervention Type DRUG

850 mg (2 capsules) by mouth twice daily; minimum of 10 days, maximum of 21 days

Interventions

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Placebo

2 capsules by mouth twice daily; minimum of 10 days, maximum of 21 days

Intervention Type DRUG

Metformin

850 mg (2 capsules) by mouth twice daily; minimum of 10 days, maximum of 21 days

Intervention Type DRUG

Other Intervention Names

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inactive drug Glucophage Glucophage XR Glumetza Fortamet Riomet

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Arkansas

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Rangaswamy Govindarajan, MD

Role: PRINCIPAL_INVESTIGATOR

University of Arkansas

Frank Simmen, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Arkansas

Locations

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Central Arkansas Veterans Heathcare System

Little Rock, Arkansas, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Countries

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United States

Other Identifiers

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134190

Identifier Type: -

Identifier Source: org_study_id

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