Effect of Metformin on Biomarkers of Colorectal Tumor Cell Growth

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University of Arkansas
ClinicalTrials.gov Identifier:
NCT01632020
First received: June 27, 2012
Last updated: February 21, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Colorectal Neoplasms
Drug: Placebo
Drug: Metformin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pilot Study: Effect of Metformin on Biomarkers of Colorectal Tumor Cell Growth

Resource links provided by NLM:


Further study details as provided by University of Arkansas:

Primary Outcome Measures:
  • Proliferation status of CRC tumor and adjacent normal tissue following Metformin therapy [ Time Frame: 10-21 days ] [ Designated as safety issue: No ]
  • Mucosal apoptotic status of CRC tumor and adjacent normal tissue following Metformin therapy [ Time Frame: 10-21 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: August 2012
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
2 capsules by mouth twice daily; minimum of 10 days, maximum of 21 days
Active Comparator: Metformin 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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01632020

Locations
United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
Central Arkansas Veterans Heathcare System
Little Rock, Arkansas, United States, 72205
Sponsors and Collaborators
University of Arkansas
Investigators
Principal Investigator: Rangaswamy Govindarajan, MD University of Arkansas
Principal Investigator: Frank Simmen, PhD University of Arkansas
  More Information

No publications provided

Responsible Party: University of Arkansas
ClinicalTrials.gov Identifier: NCT01632020     History of Changes
Other Study ID Numbers: 134190
Study First Received: June 27, 2012
Last Updated: February 21, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Arkansas:
colorectal tumor
colorectal cancer
colorectal carcinoma
neoplasms, colorectal
Metformin

Additional relevant MeSH terms:
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014