Pilot Study: Effect of Metformin on Biomarkers of Colorectal Tumor Cell Growth
Overview
- Phase
- Phase 2
- Intervention
- Placebo
- Conditions
- Colorectal Neoplasms
- Sponsor
- University of Arkansas
- Enrollment
- 7
- Locations
- 2
- Primary Endpoint
- Mucosal Apoptotic Status of CRC Tumor and Adjacent Normal Tissue Following Metformin Therapy
- Status
- Terminated
- Last Updated
- 9 years ago
Overview
Brief Summary
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
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.
Investigators
Eligibility 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)
Exclusion Criteria
- •Previously diagnosed with diabetes mellitus Type 1 or Type
- •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).
Arms & Interventions
Placebo
Placebo 2 capsules by mouth twice daily; minimum of 10 days, maximum of 21 days
Intervention: Placebo
Metformin
Metformin 850 mg (2 capsules) by mouth twice daily; minimum of 10 days, maximum of 21 days
Intervention: Metformin
Outcomes
Primary Outcomes
Mucosal Apoptotic Status of CRC Tumor and Adjacent Normal Tissue Following Metformin Therapy
Time Frame: 10-21 days
Proliferation Status of CRC Tumor and Adjacent Normal Tissue Following Metformin Therapy
Time Frame: 10-21 days