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

This study has been terminated.
(Unable to accrue all planned subjects in a timely fashion, but data collected will still be analyzed.)
Sponsor:
Information provided by (Responsible Party):
Tufts Medical Center
ClinicalTrials.gov Identifier:
NCT01440127
First received: September 21, 2011
Last updated: July 10, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Colon Cancer
Drug: Metformin
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Clinical Trial Evaluating the Impact of Pretreatment With Metformin on Colorectal Cancer Stem Cells (CCSC) and Related Pharmacodynamic Markers

Resource links provided by NLM:


Further study details as provided by Tufts Medical Center:

Primary Outcome Measures:
  • Expression of CD133 in tumors from patients treated or not treated with metformin [ Time Frame: 2-weeks of metformin treatment ] [ Designated as safety issue: No ]

Enrollment: 9
Study Start Date: August 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Metformin
Subjects in this arm are randomized to receive metformin during the period of time between planning the surgery or biopsy and the actual procedure. After approximately 1 week of taking metformin, we will re-check the blood glucose. We will draw blood for cancer stem cells (about 2 teaspoons) and ask about symptoms. Subjects will stop taking metformin 2 days before the procedure.
Drug: Metformin
Pills will be taken for one week prior to the scheduled surgery or biopsy procedure.
Other Names:
  • Fortamet
  • Glucophage
  • Glumetza
  • Riomet
No Intervention: Observation
No metformin will be given prior to the scheduled surgery or biopsy.

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01440127

Locations
United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States, 02111
Sponsors and Collaborators
Tufts Medical Center
Investigators
Principal Investigator: Wasif Saif, MD Tufts Medical Center
  More Information

No publications provided

Responsible Party: Tufts Medical Center
ClinicalTrials.gov Identifier: NCT01440127     History of Changes
Other Study ID Numbers: Metformin CCSC
Study First Received: September 21, 2011
Last Updated: July 10, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Colonic Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014