Exercise and Metformin Hydrochloride in Lowering Insulin Levels in Colorectal or Breast Cancer Survivors

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Basic Trial Information

PhaseTypeAgeTrial IDs
Phase IIBiomarker/Laboratory analysis, Educational/Counseling/Training, Treatment18 and over11-009
NCI-2011-02702, NCT01340300

Trial Description

Summary

This randomized phase II trial studies whether taking the medication metformin (metformin hydrochloride) and/or participating in a supervised exercise program can help survivors of colorectal or breast cancer lower their insulin levels and increase their physical activity. Physical activity after colorectal or breast cancer diagnosis may also help reduce the chance the cancer will come back.

Further Study Information

PRIMARY OBJECTIVES:

I. 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.

SECONDARY OBJECTIVES:

I. Compare changes in other insulin-related biomarkers, including C-peptide, insulin-like growth factor (IGF)-1, IGF binding protein (IGFBP)-3, adiponectin and leptin by treatment arm.

II. Explore for an interaction effect in addition to an additive effect of exercise and metformin in reducing fasting insulin level over the 3 month intervention.

III. Compare changes in body mass index by treatment arm as well as self-directed change in diet quality by treatment arm.

IV. Compare changes in pro-inflammatory markers potentially related to insulin resistance (including interleukin [IL]-1beta, IL-6, IL-10, tumor necrosis factor [TNF]-alpha, C-reactive protein) by treatment arm.

OUTLINE: Patients are randomized to 1 of 4 arms.

ARM I: Participants receive metformin hydrochloride orally (PO) once daily (QD) for 2 weeks and then twice daily (BID) for 3 months in the absence of disease progression or unacceptable toxicity. Participants also undergo supervised exercise training sessions consisting of 30-60 minutes of cardiovascular exercise and 5-10 minutes of static stretching for 3 months. Participants gradually increase their exercise duration and intensity until they reach a goal of 220 minutes of moderate-intensity exercise per week. They also complete an additional 120 minutes of unsupervised aerobic activity each week. Each participant uses a heart rate monitor to learn to recognize moderate-intensity exertion.

ARM II: Participants undergo supervised exercise training sessions as participants in Arm I.

ARM III: Participants receive metformin hydrochloride as participants in Arm I.

ARM IV: Participants receive written information emphasizing the importance of a healthy lifestyle and are encouraged to follow the National Institute of Cancer (NCI) and the American Cancer Society's (ACS) nutrition and physical activity guidelines.

After completion of study treatment, patients are followed up for 6 months.

Eligibility Criteria

Inclusion Criteria:

At least 1 month from any major surgery to start of intervention, including colostomy reversal (port-a-cath removal excluded)

Histologically confirmed stage I-III colorectal or breast cancer who have undergone curative-intent complete surgical resection and completed all adjuvant cytotoxic chemotherapy and radiation (if indicated) at least 2 months prior to enrollment; breast cancer patients on hormonal therapy or trastuzumab only therapy and colorectal cancer patients on adjunctive therapies not considered cytotoxic chemotherapy (including those participating in CALGB 80702 receiving only celecoxib/placebo) are eligible

No planned surgery anticipated in the 3-month intervention period

English speaking and able to read English (to complete required questionnaires)

Willingness to be randomized

Alkaline phosphatase < 2 x ULN

Serum creatinine < institutional upper limit of normal (ULN)

Less than 120 minutes of exercise per week (as determined by Leisure Score Index of Godin Leisure-Time Exercise Questionnaire [LSI])

Written informed consent prior to any study-related procedures

Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 1.5 x institutional ULN

Approval by oncologist or surgeon

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Random glucose < 160 mg/dL or fasting glucose < 126 mg/dL (other values require workup to rule out undiagnosed diabetes that may require treatment)

Serum bilirubin < institutional ULN (in patients with Gilbert’s disease, direct bilirubin < institutional ULN)

Exclusion Criteria:

Concurrent other active malignancy (other than non-melanoma skin cancer or in situ cervical cancer)

Presence of metastatic disease

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)

Absolute contraindications to maximal exercise testing as recommended by the American Thoracic Society and exercise testing guidelines for cancer patients

Currently on medications for diabetes treatment (patients with hyperglycemia [random glucose < 160 mg/dL or fasting glucose < 126 mg/dl] but who are not on any drug treatment are eligible)

Unable to comply with protocol and/or not available for follow-up assessments

Pregnant (i.e., positive beta-human chorionic gonadotropin [HCG]) or breast feeding

Any condition which in the investigator’s opinion makes the subject unsuitable for study participation

Known hypersensitivity or intolerance to metformin

Participating in another clinical study with competing study outcomes

Scheduled to receive any form of further adjuvant cancer therapy (except hormonal or biologic therapy for breast cancer or adjunctive noncytotoxic chemotherapy for colorectal cancer including participation in CALGB 80702 while on celecoxib/placebo)

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

Dana-Farber Harvard Cancer Center

  • National Cancer Institute
Jeffrey A. Meyerhardt, Principal Investigator

Trial Sites

U.S.A.

Connecticut
New Haven

Yale University

Melinda Liggett Irwin
Ph: 203-785-6392
Email: Melinda.Irwin@yale.edu

Melinda Liggett Irwin
Principal Investigator

Massachusetts
Boston

Brigham and Women's Faulkner Hospital

Erica L. Mayer
Ph: 617-632-2335
Email: Erica_Mayer@dfci.harvard.edu

Erica L. Mayer
Principal Investigator

Brigham and Women's Hospital

Jeffrey A. Meyerhardt
Ph: 617-632-6855
Email: jeffrey_meyerhardt@dfci.harvard.edu

Jeffrey A. Meyerhardt
Principal Investigator

Dana-Farber Cancer Institute

Jeffrey A. Meyerhardt
Ph: 617-632-6855
Email: jeffrey_meyerhardt@dfci.harvard.edu

Jeffrey A. Meyerhardt
Principal Investigator

North Carolina
Durham

Duke University Medical Center

Lee Winston Jones
Ph: 919-668-6791
Email: lee.w.jones@duke.edu

Lee Winston Jones
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01340300

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.