Health Education Materials With or Without a Physical Activity Program for Patients Who Have Undergone Treatment for High-Risk Stage II or Stage III Colon Cancer

OBJECTIVES:

Primary

- To compare the disease-free survival (DFS) of medically fit patients who have completed
surgical resection and adjuvant chemotherapy for high-risk stage II or stage III colon
cancer when administered a physical activity program with general health education
materials vs general health education materials alone.

Secondary

- To compare the two intervention arms with respect to overall survival (OS);
patient-reported outcomes using the SF-36, FACIT-F, PSQI, and HADS questionnaires;
objective markers of physical fitness using body mass index, hip and waist
circumference, submaximal exercise testing, and the Seniors' Fitness Test; physical
activity behavior using the Total Physical Activity Questionnaire (TPAQ); safety profile
as assessed by NCI CTCAE version 3.0; serum levels of insulin (i.e., IGF-1, IGF-2, and
IGFBP3); cytokine levels (i.e., IL-1β, IL-6, IL-2, IL-4, IL-8, IL-10, IL-12, TNF-α,
IFN-γ, and GM-CSF) and C-reactive protein levels; economic evaluations including
cost-effective and cost-utility analyses; and predictors of physical activity adherence
using the Social-Cognitive Determinants of Exercise Measure questionnaire.

- To evaluate the potential prognostic associations of the serum levels of insulin, IGF-1,
IGF-2, IGFBP3, blood glucose, cytokines (i.e., IL- 1β, IL-6, IL-2, IL-4, IL-8, IL-10,
IL-12, TNF-α, IFN-γ, and GM-CSF), and C-reactive protein with DFS, OS, level of physical
activity, and level of fatigue in these patients.

- To evaluate the potential prognostic associations of age, gender, country, incremental
increase in physical activity, and change in cardiovascular fitness with DFS, OS, level
of fatigue, and quality of life in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to disease stage (II
vs III), participating center, body mass index (≤ 27.5 vs > 27.5), and ECOG performance
status (0 vs 1). Patients are randomized to 1 of 2 treatment interventions.

- Arm I: Patients receive general health education materials regarding nutrition and
physical activity and undergo the Colon Health And Life Long Exercise Change (CHALLENGE)
physical activity program consisting of behavior-support sessions and supervised
physical activity sessions with a physical activity consultant.

- Part I (intensive intervention for 6 months): Patients undergo 12 mandatory
biweekly face-to-face behavior support sessions combined with 12 mandatory
supervised physical activity sessions to increase their physical activity goal by
10 metabolic equivalent task (MET) hours/week. Twelve supervised physical activity
sessions are also recommended on alternate weeks.

- Part II (reduced intervention for months 6-12): Patients undergo 12 mandatory
biweekly face-to-face or telephone behavior support sessions combined with 12
recommended supervised physical activity sessions to increase their physical
activity goal by 20 MET hours/week.

- Part III (minimal intervention for months 12-36): Patients undergo mandatory
monthly face-to-face or telephone behavior support sessions combined with
recommended supervised physical activity sessions to increase their physical
activity goal to a maximum total of 27 MET hours/week.

- Arm II: Patients receive general health education materials regarding nutrition and
physical activity.

Patients complete the Total Physical Activity Questionnaire (TPAQ) to assess exercise
participation and undergo fitness testing periodically by the submaximal exercise test and
Seniors' Fitness Test (SFT).

Patients complete the SF-36, FACT-F, Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety
and Depression Scale (HADS), and Social Cognitive Determinants of Exercise Measure
questionnaires periodically. Patients also complete a 30-day resource use diary and undergo a
health economics analysis by the Work Productivity and Activity Impairment (WPAI)
questionnaire.

Blood samples are collected periodically for correlative studies and fasting glucose. Samples
are analyzed for markers of insulin level, IGF-1, IGF-2, and IGFBP3, cytokine levels (i.e.,
IL-1β, IL-6, IL-2, IL-4, IL-8, IL-10, IL-12, TNF-α, IFN-γ, and GM-CSF), and C-reactive
protein levels.

During the 3 year intervention period, patients are followed every 6 months for 3 years and
then annually for 4-10 years.

DISEASE CHARACTERISTICS:

- Completely resected histologically confirmed adenocarcinoma of the colon

- High-risk stage II disease, including one of the following:

- T4 lesions

- Less than 12 sampled lymph nodes

- Poorly differentiated histology

- Stage III disease, defined as having at least one pathologically confirmed
positive lymph node or one pathologically confirmed positive tumour deposit.

- Synchronous primary colon cancer allowed

- Adjuvant chemotherapy treatment for colon cancer with a 5-fluorouracil- based regimen
received with an intent to provide a complete course of treatment. While one current
standard is 24 weeks of treatment, patients who are pre-planned to receive a shorter
duration of chemotherapy, including as part of a research study will also be
permitted. The actual treatment received may be less than 24 weeks; participants must
have received a minimum of one treatment cycle.

- Chemotherapy must have been completed (i.e. last dose received) a minimum of 60 days
and a maximum of 180 days prior to registration.

- Carcinoembryonic antigen (CEA) ≤ 5 μg/L

- Current physical activity levels do not meet the recommended guidelines (≥ 150 minutes
of moderate-to-vigorous or ≥ 75 minutes of vigorous physical activity/week) as
calculated using the Leisure Time Exercise Questionnaire (LTEQ)

- Completion of chest x-ray or CT, and CT, MRI or ultrasound of abdomen within 60 days
of registration; these imaging tests must not show evidence of metastatic or
locally-recurrent colon cancer.

- No rectal cancer

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- Absolute granulocyte count ≥ 1,000/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 100 g/L

- Serum creatinine ≤ 1.5 times upper limit of normal (ULN)

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- Alkaline phosphatase < 2.5 times ULN

- ALT < 2 times ULN

- Not pregnant or planning to become pregnant within the next 3 years

- Able (i.e., sufficiently fluent) and willing to effectively communicate with the
physical activity consultant affiliated with the originating cancer center

- Able (i.e., sufficiently fluent in English or French) and willing to complete the
patient-reported outcome questionnaires, social determinants of exercise measurement,
health economics, and physical activity questionnaires and logs

- Able to complete the baseline exercise test

- No significant comorbid conditions precluding participation in a physical activity
program as determined by the investigator

- Likely to participate in a physical activity program, as assessed by the investigator

- No history of other malignancies, except adequately treated nonmelanoma skin cancer,
curatively treated in situ cancer of the cervix, other solid tumors, Hodgkin lymphoma,
or non-Hodgkin lymphoma curatively treated with no evidence of disease for > 5 years

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior radiotherapy as a component of treatment for primary tumor

- No concurrent treatment with additional chemotherapy or radiation

- No concurrent treatment with any medications deemed by the investigator as likely to
preclude participation in a physical activity program

- No concurrent anticancer treatment including chemotherapy, biological, or targeted
agents