Exercise and Metformin in Colorectal and Breast Cancer Survivors

Randomized Phase II Study of Exercise and Metformin in Colorectal and Breast Cancer Survivors

Metformin is a medication that is commonly used in the treatment of diabetes. Recently small studies in cancer patients without diabetes suggest that metformin may benefit in lowering insulin levels. In those studies of patients with cancer but not diabetes, glucose (or sugar) levels in the blood are generally no lowered. Insulin and insulin-like growth factors affect the growth of cancer cells.

This randomized study will compare different interventions; exercise, exercise and metformin, metformin alone, or a control arm. The investigators are not directly testing how either exercise or metformin affects your disease. The investigators are testing how they affect insulin levels in your body as well as other blood markers. The investigators believe that these blood tests may either be related to cancer recurrences or be an early sign of cancer recurrences and they are testing how both exercise and metformin may change those markers.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Colorectal Cancer
• Intervention / Treatment: Behavioral: Exercise training; Drug: Metformin; Other: Educational information

Detailed Description

Subjects will be randomized into one of four groups: exercise training, exercise training and metformin, metformin alone, or control arm. All subjects will have lifestyle measurements, interviews regarding activity level, diet questionnaires, and blood tests.

Subjects randomized to exercise training will participate in two supervised exercise sessions per week with an exercise physiologist for 3 months. They will also be asked to exercise on their own for up to an additional 120 minutes each week.

Subjects randomized to exercise training and metformin will participate in two supervised exercise sessions per week and will take metformin. Metformin will be taken once daily for the first two weeks and then twice daily for 3 months.

Subjects randomized to metformin will take metformin once daily for the first two weeks and then twice daily.

Subjects on the control arm will receive a packet of educational information on nutrition and physical activity developed by the National Cancer Institute and American Cancer Society. In addition to education information, they will be offered two supervised sessions with an exercise physiologist as well as a pedometer 3 months after enrollment in the study.

• Study Type: Interventional
• Enrollment (Actual): 139
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed stage I-III colorectal or breast cancer
• Undergone curative-intent complete surgical resection and completed all adjuvant therapy (if indicated) at least 2 months prior to enrollment
• Note: Breast cancer subjects on hormonal therapy or trastuzumab only therapy and colorectal cancer subjects on adjunctive therapies not considered cytotoxic chemotherapy (including those participating in CALGB 80702 receiving only celecoxib/placebo) are eligible.
• Participants will be allowed to receive concomitant adjuvant endocrine therapy for breast cancer; however, all endocrine agents must be initiated at least 1 month prior to enrollment in the study and continued throughout the duration of study participation.
• Less than 120 minutes of exercise per week
• Approval by oncologist or surgeon
• English speaking and able to read English
• No planned surgery anticipated in the 3 month intervention period
• At least one month from any major surgery to start of intervention including colostomy reversal

Exclusion Criteria:

• Concurrent other malignancy or history of other malignancy treated within the past 3 years (other than non-melanoma skin cancer or in-situ cervical cancer)
• Metastatic disease
• Scheduled to receive any form of further adjuvant cancer therapy
• Currently on medication for diabetes treatment
• Pregnant or breast-feeding
• Any condition associated with increased risk of metformin-associated lactic acidosis (prior renal failure or liver failure, history of acidosis of any type; habitual intake of 3 or more alcoholic beverages per day)
• Known hypersensitivity or intolerance to metformin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Metformin	Drug: Metformin; Oral metformin QD for two weeks, then BID; Other Names: Fortamet, Glucophage, Glucophage XR, Glumetza, Riomet
Active Comparator: Exercise training; Exercise training with exercise physiologist	Behavioral: Exercise training; Two supervised exercise sessions per week
Active Comparator: Exercise training with metformin; Exercise training with exercise physiologist with oral metformin	Behavioral: Exercise training; Two supervised exercise sessions per week; Drug: Metformin; Oral metformin QD for two weeks, then BID; Other Names: Fortamet, Glucophage, Glucophage XR, Glumetza, Riomet
Active Comparator: Control; Educational information	Other: Educational information; educational information

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fasting Insulin Level	Determine whether supervised exercise training alone and metformin, either alone or in combination can decrease fasting insulin level from baseline to 3 months in patients who completed standard therapy for stage I-III colorectal or breast cancer. Fasting insulin levels in blood will be drawn at baseline, 3 months and 6 months. Negative least square means indicate a decrease at 3 month comparing to baseline value.	0 and 3 months (change between 0 and 3 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Other Insulin-Related Biomarkers	Markers related to insulin and insulin-like growth factors (including insulin-like growth factor 1 [IGF-1], IGF binding protein-1 [IGFBP-1], IGF binding protein-3 [IGFBP-3], leptin) will be measured by a blood draw at baseline, 3 months and 6 months. Negative least square means indicate a decrease at 3 month comparing to baseline value.	0 and 3 months (change between 0 and 3 months)
Change in Fasting Glucose Level	Determine whether supervised exercise training alone and metformin, either alone or in combination can decrease fasting Glucose level from baseline to 3 months in patients who completed standard therapy for stage I-III colorectal or breast cancer. Fasting Glucose levels in blood will be drawn at baseline, 3 months and 6 months. Negative least square means indicate a decrease at 3 month comparing to baseline value.	0 and 3 months (change between 0 and 3 months)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Body Composition by Treatment Arm - Weight	Negative least square means indicate a decrease at 3 month comparing to baseline value.	0 and 3 months (change between 0 and 3 months)
Changes in Body Composition by Treatment Arm - BMI	Negative least square means indicate a decrease at 3 month comparing to baseline value.	0 and 3 months (change between 0 and 3 months)
Changes in Body Composition by Treatment Arm - Waist to Hip Ratio	Negative least square means indicate a decrease at 3 month comparing to baseline value.	0 and 3 months (change between 0 and 3 months)

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: April 7, 2011
• First Submitted That Met QC Criteria: April 21, 2011
• First Posted (Estimate): April 22, 2011

Study Record Updates

• Last Update Posted (Actual): June 6, 2018
• Last Update Submitted That Met QC Criteria: May 3, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Insulin; Exercise; Breast; Colorectal
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: 11-009