Effect of Metformin on Biomarkers of Colorectal Tumor Cell Growth
Condition: Colorectal Neoplasms
MeSH terms: Colorectal Neoplasms
Intervention: Placebo; Metformin
Intervention description: 2 capsules by mouth twice daily; minimum of 10 days, maximum of 21 days; 850 mg (2 capsules) by mouth twice daily; minimum of 10 days, maximum of 21 days
Intervention MeSH terms: Metformin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: colorectal tumor; colorectal cancer; colorectal carcinoma; neoplasms, colorectal; Metformin

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.
    

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.