Exercise and Metformin Hydrochloride in Lowering Insulin Levels in Colorectal or Breast Cancer Survivors
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.
Inclusion Criteria
- Written informed consent prior to any study-related procedures
- 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 Cancer and Leukemia Group B [CALGB] 80702 receiving only celecoxib/placebo) are eligible
- Less than 120 minutes of exercise per week (as determined by Leisure Score Index of Godin Leisure-Time Exercise Questionnaire [LSI])
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Approval by oncologist or surgeon
- Serum creatinine < institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 1.5 x institutional ULN
- Alkaline phosphatase < 2 x ULN
- Serum bilirubin < institutional ULN (in patients with Gilbert’s disease, direct bilirubin < institutional ULN)
- Random glucose < 160 mg/dL or fasting glucose < 126 mg/dL (other values require workup to rule out undiagnosed diabetes that may require treatment)
- Willingness to be randomized
- English speaking and able to read English (to complete required questionnaires)
- No planned surgery anticipated in the 3-month intervention period
- At least 1 month from any major surgery to start of intervention, including colostomy reversal (Port-A-Cath removal excluded)
Exclusion Criteria
- Concurrent other active malignancy (other than non-melanoma skin cancer or in situ cervical cancer)
- Presence of metastatic disease
- 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)
- 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)
- Absolute contraindications to maximal exercise testing as recommended by the American Thoracic Society and exercise testing guidelines for cancer patients
- Any condition which in the investigator’s opinion makes the subject unsuitable for study participation
- Participating in another clinical study with competing study outcomes
- Pregnant (i.e., positive beta-human chorionic gonadotropin [HCG]) or breast feeding
- Unable to comply with protocol and/or not available for follow-up assessments
- 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 sponsor and potential other locations can be found on ClinicalTrials.gov for NCT01340300.
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 IL-1beta, IL-6, IL-10, TNF-alpha, C-reactive protein) by treatment arm.
V. Explore changes in metabolite profiling using liquid chromatography-mass spectrometry analysis 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.
Trial PhasePhase II
Trial Typesupportive care
Lead OrganizationDana-Farber Harvard Cancer Center
Principal InvestigatorJeffrey A. Meyerhardt
- Primary ID11-009
- Secondary IDsNCI-2011-02702
- ClinicalTrials.gov IDNCT01340300