Exercise During Active Surveillance for Prostate Cancer

Study Overview
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Brief Summary
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The broad goal of the Exercise During Active Surveillance for Prostate Cancer (ERASE) trial is to examine the effects of exercise in prostate cancer patients undergoing active surveillance.

Detailed Description
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The ERASE Trial will be a phase II randomized controlled trial. A total of 66 men with low- or intermediate-grade clinically localized prostate cancer undergoing active surveillance will be randomized to either a 12-week of supervised high-intensity aerobic interval training or usual care. The primary outcome will be peak oxygen consumption (VO2peak) as a measure of physical fitness. The secondary outcomes include tumour-related biomarkers, fear of cancer progression, quality of life, and psychological distress. Exploratory outcomes will include indicators of cancer progression including prostate-specific antigen. Based on this sample size, our study has 80% power with a two-tailed alpha <0.05 to detect a clinically meaningful effect of 3.5 ml/kg/min on our primary outcome of VO2max. This power will also be sufficient for detecting differences in our secondary biomarkers and patient-reported outcomes if the effects are at least moderate (i.e., a standardized effect size of d=0.60).

Official Title
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A Phase II Randomized Controlled Trial of Exercise in Prostate Cancer Patients Undergoing Active Surveillance

Conditions
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Prostate Cancer

Intervention / Treatment
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* Behavioral: High-intensity aerobic interval training (HIIT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years of age diagnosed with low or favorable intermediate grade localized PCa defined as PSA less than 10, Gleason Score 3+3 or 3+4 with low volume, and digital rectal examination (DRE) of T1C or T2A initiating or continuing active surveillance with no plans for treatment for prostate cancer in the next 6 months (e.g., radical prostatectomy, radiotherapy, or androgen deprivation therapy) screened for medical clearance for exercise testing and participation in vigorous aerobic exercise residing in a commutable area near Edmonton, Alberta willing to commute to the Behavioural Medicine Fitness Centre three times per week to attend a 12-week supervised high-intensity aerobic interval exercise program Exclusion Criteria: having comorbidities or uncontrolled medical conditions that their referred clinicians indicate as inappropriate to participate in exercise (e.g., known cardiac disease or uncontrolled hypertension) having contraindications for cardiopulmonary stress and/or physical fitness tests currently participating in a structured, vigorous exercise program.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercise Group<br>Supervised high-intensity aerobic interval training (HIIT) during active surveillance | Behavioral: High-intensity aerobic interval training (HIIT)<br>* A 12-week, supervised, HIIT aerobic exercise program consisting of alternating vigorous- and low-intensity intervals<br>|
| No Intervention: Usual Care Group<br>The usual care group will be provided with standard active surveillance medical care. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of Peak Oxygen Consumption (VO2peak) | VO2peak is a measure of cardiopulmonary fitness and a powerful surrogate outcome for cancer-specific and overall survival. VO2peak will be defined as the highest oxygen-uptake value recorded during the test and quantified where participants reach a plateau in oxygen consumption, which will be expressed as relative to body mass (i.e., ml O2·kg-1·min-1). | At baseline and 12-week (postintervention) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of Natural Killer Cell Cytotoxic Activity (NKCA) and Counts | NKCA significantly contributes to the regulation of tumour suppression in response to exercise and it has been demonstrated to have a diagnostic value in patients with cancer. NK cell activities are assessed using blood analysis as the total number of circulating NK cells and their cytotoxic activity. NK cell counts and NKCA will be measured using the phenotypic markers of NK cells (CD3-CD16+CD56+). NKCA will be expressed as the percentage of target cells killed by a sample of 100,000 peripheral blood mononuclear cells at the effector-to-target ratios of 5:1, 20:1, 40:1, and 100:1. | At baseline and 12-week (postintervention) | 
| Changes of Immune-Related Phenotype | Immune-related phenotypic markers, including CD3, CD16, CD56, and CD107 (on the frozen) and CD4, CD8, CD20, CD25, CD11, CD45RA, CD45RO, CD16, CD56, CD107 activation (fresh on whole blood), will be assessed using blood samples. | At baseline and 12-week (postintervention) | 
| Changes of Prostate-Specific Antigen (PSA) | PSA will be assessed using blood samples. | At baseline, 12-week (postintervention) | 
| Changes of Complete Blood Count with Differential (CBCD) | CBCD, including RBC, WBC, HGB, HCT, PLT, LYMPH, BASO, EOS, MONO, NEUT, will be assessed using blood samples. | At baseline and 12-week (postintervention) | 
| Changes of Insulin | Fasting insulin levels will be assessed using blood samples. | At baseline and 12-week (postintervention) | 
| Changes of Fasting Glucose | Fasting glucose levels will be assessed using blood samples. | At Baseline and 12-week postintervention | 
| Changes of HbA1c | HbA1c will be assessed using using blood samples. | At Baseline and 12-week postintervention | 
| Changes of Insulin-like Growth Factor (IGF)-axis | IGF-axis, including circulating IGF-1 and IGF binding protein(IGFBP)-3, will be assessed using blood samples. | At baseline and 12-week (postintervention) | 
| Changes of Pro-Inflammatory Cytokines | Pro-inflammatory cytokines, including IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and TNF-α, will be assessed. | At baseline and 12-week (postintervention) | 
| Changes of High-Sensitivity C-Reactive Protein (hs-CRP) | hs-CRP will be assessed using blood samples. | At Baseline and 12-week postintervention | 
| Changes of Adiponectin | Adiponectin will be assessed using blood samples. | At Baseline and 12-week postintervention | 
| Physical Function | Physical function, consisting of strength, flexibility, and agility components, will be assessed by the Senior's Fitness Test (SFT). | At Baseline and 12-week postintervention | 
| Health-Related Quality of Life | Health-related quality of life will be assessed using the European Organization for Research and Treatment of Cancer- Quality of Life Questionnaire (EORTC-QLQ) - C30 questionnaire. | At baseline, 12-week (postintervention), 6-month, and 12-month | 
| Prostate Cancer-Specific Quality of Life | Prostate cancer-specific quality of life will be assessed using the Expanded Prostate Cancer Index Composite-26 (EPIC-26) questionnaire. | At baseline, 12-week (postintervention), 6-month, and 12-month | 
| Fear of Cancer Progression | Fear of cancer progression will be assessed using the Fear of Cancer Recurrence Inventory (FCRI) questionnaire. | At baseline, 12-week (postintervention), 6-month, and 12-month | 
| Cancer Worry | Cancer worry will be assessed using the Cancer Worry Scale (CWS) questionnaire. | At baseline, 12-week (postintervention), 6-month, and 12-month | 
| General Anxiety | General anxiety will be assessed using the Anxiety (general): Spielberger State-Trait Anxiety Inventory (STAI) questionnaire. | At baseline, 12-week (postintervention), 6-month, and 12-month | 
| Prostate Cancer-Specific Anxiety | Prostate cancer-specific anxiety will be assessed using the Memorial Anxiety Scale for Prostate Cancer (MAX-PC) questionnaire. | At baseline, 12-week (postintervention), 6-month, and 12-month | 
| Depression | Depression will be assessed using the Epidemiologic Studies Depression Scale (CES-D) questionnaire. | At baseline, 12-week (postintervention), 6-month, and 12-month | 
| Perceived Stress | Perceived stress will be assessed using the Perceived Stress Scale (PSS) questionnaire. | At baseline, 12-week (postintervention), 6-month, and 12-month | 
| Self-esteem | Self-esteem will be assessed using the Rosenberg Self-Esteem Scale (RSES) questionnaire. | At baseline, 12-week (postintervention), 6-month, and 12-month | 
| Fatigue | Fatigue will be assessed using the Functional Assessment of Cancer Therapy- Fatigue (FACT-F) questionnaire. | At baseline, 12-week (postintervention), 6-month, and 12-month | 
| Physical Activity Level | Physical activity level, consisting of light-, moderate-, and vigorous aerobic exercise and resistance exercise, will be assessed using the Godin Leisure-Time Exercise Questionnaire (GLTEQ). | At baseline, 12-week (postintervention), 6-month, and 12-month | 
| Exercise Motivation | Exercise motivation, consisting of Theory of Planned Behaviour (TPB) constructs (instrumental and affective attitudes, subjective norms, intention and perceived behavioral control), will be assessed using questionnaire. | At baseline, 12-week (postintervention), 6-month, and 12-month | 
| Body composition | Body composition, including body weight and waist- and hip-circumferences, will be assessed using weight scales and a tape measure. | At baseline and 12-week (postintervention) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate Cancer, Active Surveillance, Exercise, High-Intensity Interval Training, Randomized Controlled Trial