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

Primary Purpose

Colon Cancer

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Metformin

About this trial

This is an interventional treatment trial for Colon Cancer

Eligibility Criteria

18 Years - 79 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Tufts Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Metformin

Observation

Arm Description

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.

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

NCT ID

NCT01440127

First Posted

September 21, 2011

Last Updated

March 25, 2015

Sponsor

Tufts Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT01440127

Brief Title

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

Official Title

Randomized Clinical Trial Evaluating the Impact of Pretreatment With Metformin on Colorectal Cancer Stem Cells (CCSC) and Related Pharmacodynamic Markers

Study Type

Interventional

2. Study Status

Record Verification Date

March 2015

Overall Recruitment Status

Terminated

Why Stopped

Unable to accrue all planned subjects in a timely fashion, but data collected will still be analyzed.

Study Start Date

August 2011 (undefined)

Primary Completion Date

October 2012 (Actual)

Study Completion Date

October 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Tufts Medical Center

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colon Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Metformin

Arm Type

Experimental

Arm Description

Arm Title

Observation

Arm Type

No Intervention

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Metformin

Other Intervention Name(s)

Fortamet, Glucophage, Glumetza, Riomet

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Time Frame

2-weeks of metformin treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

79 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Wasif Saif, MD

Organizational Affiliation

Tufts Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Tufts Medical Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02111

Country

United States

12. IPD Sharing Statement

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

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