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

NCT01440127 | Terminated Phase 1 DMC

• 1 other identifier: Metformin CCSC
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Colon Cancer

Outcome Measures

Primary Outcomes (1)

• Expression of CD133 in tumors from patients treated or not treated with metformin

  2-weeks of metformin treatment

Study Arms (2)

Metformin

EXPERIMENTAL

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

Observation

NO INTERVENTION

No metformin will be given prior to the scheduled surgery or biopsy.

Interventions

Metformin DRUG

Pills will be taken for one week prior to the scheduled surgery or biopsy procedure.

Also known as: Fortamet, Glucophage, Glumetza, Riomet

Metformin

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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;
• 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

Sponsors & Collaborators

• Tufts Medical Center: lead

Study Sites (1)

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Metformin

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Wasif Saif, MD

  Tufts Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2011
• First Posted: September 26, 2011
• Study Start: August 1, 2011
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: March 26, 2015

Record last verified: 2015-03

Locations

US (1)