Exercise and Metformin in Colorectal and Breast Cancer Survivors

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.

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