Phase 2
N=45
Trial of Metformin for Colorectal Cancer Risk Reduction for History of Colorectal Adenomas and Elevated BMI
Adenomatous Polyp · Colorectal Cancer · Obesity
Bottom Line
View on ClinicalTrials.gov: NCT01312467 ↗Enrolled (actual)
45
Serious AEs
2.2%
Results posted
Jun 2015
Primary outcome: Primary: Change in Activated S6serine235 (i.e., the Ratio of pS6serine235/S6serine235) — 0.0228 weighted ratio of staining cells — p=> 0.773
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- metformin hydrochloride (Drug)
- Age
- Adult, Older Adult · 35+ yrs
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Mar 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Activated S6serine235 (i.e., the Ratio of pS6serine235/S6serine235) |
0.0228 | > 0.773 |
| SECONDARY Effects of Metformin Hydrochloride on Colorectal Mucosa Proliferation (Ki-67, Phosphorylated IGF-1 Receptor, Phosphorylated Insulin Receptor, Phosphorylated AKT, Phosphorylated mTOR, and Phosphorylated AMP Kinase) |
— | — |
| SECONDARY Effects of Metformin Hydrochloride on Serum (Fasting and 2 Hour Postprandial Insulin and Glucose, Fasting IGF-1, IGFBP-1, IGFBP-3, Leptin, Adiponectin and Metformin Levels) |
— | — |
| SECONDARY Safety and Tolerability of Metformin Hydrochloride Treatment |
186; 23; 1 | — |
Summary
The purpose of this study is to find out whether METFORMIN decreases protein markers in colorectal tissue. This is a phase IIA study of the pharmacodynamics, safety and tolerability of Metformin in decreasing colorectal mucosa in patients with a history of colorectal adenomas in the past 3 years and a BMI >= 30, with decimals rounded to the nearest whole integer. Metformin as a potential chemopreventive agent for inhibition of the relevant molecular pathways involved in human colorectal carcinogenesis.
Eligibility Criteria
Inclusion Criteria
- History of prior colorectal adenomas within the past 3 years; only patients who have had adenomas endoscopically removed are eligible; documentation of colorectal adenomas must be determined via review of pathology reports
- Body mass index (BMI) >= 30; rounded to the nearest whole integer
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Leukocytes ≥ 3, 000/μL (>= 2,500/μL for African-American participants)
- Absolute neutrophil count >= 1, 500/μL (>= 1,000/μL for African-American participants)
- Platelets >= 100,000/μL
- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) = 1.4 mg/dL for females or > 1.5 mg/dL for males)
- Metabolic acidosis, acute or chronic, including ketoacidosis
- Uncontrolled intercurrent illness including, but not limited to:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness/social situations that would limit compliance with study requirements
- Renal failure
- Hepatic failure
- Sepsis
- Hypoxia
- Pregnant or breastfeeding women are excluded
- Participants anticipating elective surgery during the study period
- Contraindication to colonoscopy/flexible sigmoidoscopy
- Participants may not be using metformin, cimetidine (Tagament) furosemide (Lasix), nifedipine (Cardizem), Ranitidine (Zinetac or Zantac), digoxin (Lanoxin), Quinidine or any other drug contraindicated for use with metformin
- Chronic alcohol use or a history of alcohol abuse
- Participants with any medical psychosocial condition that, in the opinion of the investigator, could jeopardize participation in and compliance with the study criteria
- Participants that regularly use aspirin (ASA), nonsteroidal anti-inflammatory drugs (NSAIDs), calcium, and cyclooxygenase (Cox)-2 inhibitors are not eligible for enrollment; however, patients that use aspirin 81 mg daily, or aspirin 325 mg, NSAIDs, calcium, or Cox-2 inhibitors at a frequency < 10 times per month are eligible
Data sourced from ClinicalTrials.gov (NCT01312467). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.