Overview

Impact of Pretreatment With Metformin on Colorectal Cancer Stem Cells (CCSC) and Related Pharmacodynamic Markers

Status:
Terminated
Trial end date:
2012-10-01
Target enrollment:
0
Participant gender:
All
Summary
Metformin is drug that is normally used to treat people with diabetes. New research has discovered that metformin may also kill cancer stem cells. These cancer stem cells make up only a small portion of a cancer, but may be responsible for resistance to chemotherapy or for causing recurrence of the cancer. The purpose of this study is to determine the effect of metformin on colorectal cancer tumors. The study is designed to develop the methods to test tumors for cancer stem cells and then to determine the difference between treating with metformin and not treating with metformin with regard to the cancer stem cells. This research is investigational because the effect of metformin on cancer stem cells is not known in humans. Also, in patients who are not diabetic, metformin would normally not be given prior to surgery.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Tufts Medical Center
Treatments:
Metformin
Criteria
Inclusion Criteria:

- Histologically documented colorectal cancer

- Intent to undergo disease resection or biopsy at least 7days from the treatment start
date (allowing for a minimum of 5 days of treatment plus 2 days break)

- Medically fit for resection of their primary tumor or for biopsy

- Age 18-79 years

- Adequate renal function (serum creatinine levels <1.5 mg/dL [males], <1.4 mg/dL
[females] or estimated creatinine clearance >= 60 ml/min)

- Adequate hepatic parameters, including aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) levels ≤ 2.5 x upper limit of normal (ULN), total bilirubin ≤
1.5 x ULN, and alkaline phosphatase levels ≤ 2.5 x ULN

- Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

- Intent to administer neoadjuvant chemotherapy or radiation therapy prior to the
surgery or biopsy;

- Intent to perform surgery or biopsy within 7 days of study treatment start;

- Any situation where participation in this trial would alter, or cause significant risk
of altering the ability or timing of a subject to undergo resection of their tumor

- Current use of metformin (within the past month);

- Blood glucose using point of care test < 70mg/dl;

- Renal disease or renal dysfunction not meeting inclusion criteria;

- Significant medical conditions such as cardiovascular collapse (shock), acute
myocardial infarction, septicemia, acute or chronic metabolic acidosis

- History of, or states associated with, lactic acidosis such as shock or pulmonary
insufficiency, alcoholism (acute or chronic), conditions associated with hypoxemia and
pancreatitis

- Severe dehydration

- Clinical or laboratory evidence of hepatic disease

- Congestive heart failure requiring pharmacologic treatment, or unstable or acute
congestive heart failure

- Known hypersensitivity to metformin hydrochloride

- Pregnant or lactating women

- Psychiatric illness or social situation that would limit compliance with study
requirements and/or obscure results