Health Education Materials With/Out a Physical Activity Program for Patients Who Have Undergone Treatment for High-Risk Stage II or Stage III Colon Cancer

Study Overview
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Brief Summary
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RATIONALE: Participating in a physical activity program designed to increase free time physical activity and receiving written health education materials may influence the chance of cancer recurring as well as impact on physical fitness, psychological well-being and the quality of life of patients who have undergone surgery and chemotherapy for colon cancer. It is not yet known whether giving a physical activity program together with health education materials is more effective than giving health education materials alone for patients who have undergone colon cancer treatment. PURPOSE: This randomized phase III trial is studying a physical activity program given together with health education materials to see how well it works compared with giving health education materials alone for patients who have undergone treatment for high-risk stage II or stage III colon cancer.

Detailed Description
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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.

Official Title
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A Phase III Study of the Impact of a Physical Activity Program on Disease-Free Survival in Patients With High-Risk Stage II or Stage III Colon Cancer: A Randomized Controlled Trial

Conditions
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Anxiety Disorder, Cognitive/Functional Effects, Colorectal Cancer, Depression, Fatigue, Psychosocial Effects of Cancer and Its Treatment, Sleep Disorders, Excercise

Intervention / Treatment
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* Behavioral: exercise intervention
* Other: counseling intervention
* Other: educational intervention
* Other: laboratory biomarker analysis
* Other: questionnaire administration
* Other: study of socioeconomic and demographic variables
* Procedure: fatigue assessment and management
* Procedure: quality-of-life assessment
* Other: Educational Intervention
* Other: Fitness testing


Participation Criteria
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Eligibility Criteria
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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. Complete one of the following: (a) at least 2 stages of the submaximal exercise test with an acceptable heart rate and blood pressure response as defined in Appendix XII or (b) the 6 minute walk test with an acceptable heart rate and blood pressure response 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Physical Activity Program + General Health Education Materials<br>Intervention Arm | Behavioral: exercise intervention<br>* 3 phases Phase 1: Intensive intervention for 6 months Phase 2: Reduced intervention for months 6-12 Phase 3: Minimal intervention for months 12-36<br>Other: counseling intervention<br>* Achieving an increase in PA from baseline of ≥ 10 MET hours/week will require a significant amount of behavioural support. The intervention will comprise a 36-month individualized PA and behavioural support program with a PAC. This will include a personalized PA prescription which takes into account the baseline fitness test results, PA history, performance status and patient's personal PA preferences and any barriers to activity. Most patients are likely to choose a walking program however any PA of at least moderate intensity level is acceptable.<br>Other: educational intervention<br>* Once at the beginning of the program<br>Other: laboratory biomarker analysis<br>* Every 12 months<br>Other: questionnaire administration<br>* Every 6 months<br>Other: study of socioeconomic and demographic variables<br>* Every 6 months<br>Procedure: fatigue assessment and management<br>* Every 6 months<br>Procedure: quality-of-life assessment<br>* Every 6 months<br>Other: Fitness testing<br>* Objective fitness testing for both arms<br>|
| Active Comparator: General Health Education Materials<br>Control Arm | Other: laboratory biomarker analysis<br>* Every 12 months<br>Other: questionnaire administration<br>* Every 6 months<br>Other: study of socioeconomic and demographic variables<br>* Every 6 months<br>Procedure: fatigue assessment and management<br>* Every 6 months<br>Procedure: quality-of-life assessment<br>* Every 6 months<br>Other: Educational Intervention<br>* For Arm 2 just once at beginning of program.<br>Other: Fitness testing<br>* Objective fitness testing for both arms<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival |  | 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 10 years | 
| Patient-reported outcomes, including quality of life, using SF-36, FACIT-F, PSQI, and HADS questionnaires |  | 5 years | 
| Objective markers of physical fitness (i.e., body mass index, hip and waist circumference, cardiovascular fitness, and physical function) |  | 3 years | 
| Physical activity behavior as assessed by TPAQ |  | 5 years | 
| Safety profile according to NCI CTCAE version 3.0 |  | 10 years | 
| Correlative biological markers including biochemical and molecular markers associated with insulin-related growth factor and cytokines associated with the mechanisms of fatigue |  | 3 years | 
| Economic evaluations including cost-effective analysis and cost utility analysis |  | 5 years | 
| Predictors of physical activity adherence as assessed by Social Cognitive Determinants of Exercise questionnaire |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fatigue, sleep disorders, depression, anxiety disorder, psychosocial effects of cancer and its treatment, cognitive/functional effects, stage II colon cancer, stage III colon cancer, adenocarcinoma of the colon