Effect of Metformin on Biomarkers of Colorectal Tumor Cell Growth
Primary Purpose
Colorectal Neoplasms
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Placebo
Metformin
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Neoplasms focused on measuring colorectal tumor, colorectal cancer, colorectal carcinoma, neoplasms, colorectal, Metformin
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)
- 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.
Sites / Locations
- Central Arkansas Veterans Heathcare System
- University of Arkansas for Medical Sciences
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Active Comparator
Arm Label
Placebo
Metformin
Arm Description
Placebo 2 capsules by mouth twice daily; minimum of 10 days, maximum of 21 days
Metformin 850 mg (2 capsules) by mouth twice daily; minimum of 10 days, maximum of 21 days
Outcomes
Primary Outcome Measures
Proliferation Status of CRC Tumor and Adjacent Normal Tissue Following Metformin Therapy
Mucosal Apoptotic Status of CRC Tumor and Adjacent Normal Tissue Following Metformin Therapy
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01632020
Brief Title
Effect of Metformin on Biomarkers of Colorectal Tumor Cell Growth
Official Title
Pilot Study: Effect of Metformin on Biomarkers of Colorectal Tumor Cell Growth
Study Type
Interventional
2. Study Status
Record Verification Date
May 2016
Overall Recruitment Status
Terminated
Why Stopped
Inadequate accrual
Study Start Date
August 2012 (undefined)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
January 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Arkansas
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Neoplasms
Keywords
colorectal tumor, colorectal cancer, colorectal carcinoma, neoplasms, colorectal, Metformin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo 2 capsules by mouth twice daily; minimum of 10 days, maximum of 21 days
Arm Title
Metformin
Arm Type
Active Comparator
Arm Description
Metformin 850 mg (2 capsules) by mouth twice daily; minimum of 10 days, maximum of 21 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
inactive drug
Intervention Description
2 capsules by mouth twice daily; minimum of 10 days, maximum of 21 days
Intervention Type
Drug
Intervention Name(s)
Metformin
Other Intervention Name(s)
Glucophage, Glucophage XR, Glumetza, Fortamet, Riomet
Intervention Description
850 mg (2 capsules) by mouth twice daily; minimum of 10 days, maximum of 21 days
Primary Outcome Measure Information:
Title
Proliferation Status of CRC Tumor and Adjacent Normal Tissue Following Metformin Therapy
Time Frame
10-21 days
Title
Mucosal Apoptotic Status of CRC Tumor and Adjacent Normal Tissue Following Metformin Therapy
Time Frame
10-21 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rangaswamy Govindarajan, MD
Organizational Affiliation
University of Arkansas
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Frank Simmen, PhD
Organizational Affiliation
University of Arkansas
Official's Role
Principal Investigator
Facility Information:
Facility Name
Central Arkansas Veterans Heathcare System
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
University of Arkansas for Medical Sciences
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Effect of Metformin on Biomarkers of Colorectal Tumor Cell Growth
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