Active Surveillance Exercise Clinical Trial

Study Overview
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Brief Summary
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This phase 2, open-label, dual-center, two-arm randomized controlled trial (RCT) investigates the effects of 16 weeks of structured aerobic training, relative to usual care (print material with physical activity guidance). Prostate genomic signatures represent the functional activity of all genes in the genome and are converted into genomic risk scores which correspond to the probability of a progression event (chance of having more aggressive disease). A structured exercise program may alter the genomic risk score and improve prediction of aggressive disease.

Detailed Description
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PRIMARY OBJECTIVE: I. Determine the effect of remotely monitored, tailored aerobic training, compared to usual care (print material with physical activity guidance), on cardiopulmonary fitness in men on active surveillance for low-risk prostate cancer. SECONDARY OBJECTIVES: I. To determine the effect of aerobic training, compared with usual care, on prostate genomic signatures that predict risk of prostate cancer progression or aggressive disease; and messenger ribonucleic acid (mRNA) expression patterns in tumor and surrounding stromal (normal) tissue. II. To determine the effect of aerobic training, compared with usual care, on patient-reported outcomes including active surveillance-specific anxiety, stress, & adherence. III. To procure blood, urine and paraffin embedded prostate tissue for future exploratory studies. IV. To conduct correlative science examining associations between measures of cardiopulmonary fitness, clinical features, and biomarkers of prognosis. V. To evaluate and compare circulating and urinary biomarkers (e.g., metabolomics, proteomics) among men in Arms A, B, and C. OUTLINE: This study is a randomized controlled trial of 16-weeks aerobic exercise (home-based walking) versus (vs.) usual care among 64 men with prostate cancer on active surveillance. There is also a non-randomized observational component to the study where we will collect biospecimens, survey, data, and administer one cardiopulmonary exercise test (CPET). ARM A: Patients undergo structured aerobic training comprising four treadmill walking sessions a week at 55% to 75% of the individually determined exercise capacity for 16 weeks. Men are provided with a heart rate monitor to help ensure they exercise in their target zone. At baseline & week 16 (-7, +7 days), all patients complete: (1) lifestyle and quality-of-life questionnaires, (2) measurement of weight and waist circumference (3) collection of research fasting blood sample, (4) transrectal ultrasound-guided clinical biopsy, and (5) cardiorespiratory fitness testing. Archival tissue specimens from standard of care biopsies are also collected, pre/post intervention. ARM B (USUAL CARE): Patients undergo usual care and are provided with general physical activity information (Moving through Cancer-A Guide to Exercise for Cancer Survivors) at baseline. At the conclusion of the 16 weeks, subjects in this group will be provided with a free session with an exercise physiologist and an individualized aerobic exercise program based on their cardiorespiratory fitness test results. Archival tissue specimens from standard of care biopsies are also collected, pre/post intervention. ARM C (NON-RANDOMIZED CONTROL GROUP): Control group of men without cancer, with a lower baseline fitness level (assessed as part of screening), who will receive all baseline and 16 week follow-up assessments (except tissue procurement), and the same intervention as Arm A. Subjects undergo structured aerobic training comprising four treadmill walking sessions a week at 55% to 75% of the individually determined exercise capacity for 16 weeks. Men are provided with a heart rate monitor to help ensure they exercise in their target zone. At baseline & week 16 (-7, +7 days), all patients complete: (1) lifestyle and quality-of-life questionnaires, (2) measurement of weight and waist circumference (3) collection of research fasting blood sample, (4) cardiorespiratory fitness testing. OBSERVATIONAL GROUP (NON-RANDOMIZED): Biospecimens, survey, data, and administer one CPET will be collected. Individuals who will be enrolled to this group include those who do not meet all eligibility criteria for the RCT, or those who do not wish to be in a RCT, but are interested to participate in some lifestyle research. After completion of study, patients in Arms A & B are followed up at 16 weeks, 12 months, and 24 months. Non-randomized participants (Arm C) are followed-up at 16 weeks, and Observational study participants are asked to complete surveys at 12 and 24 months.

Official Title
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A Randomized Clinical Trial of Exercise vs. Usual Care Among Men Opting for Active Surveillance for Prostate Cancer

Conditions
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Localized Prostate Cancer, Active Surveillance for Prostate Cancer

Intervention / Treatment
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* Behavioral: Exercise
* Other: Cardiopulmonary Exercise Test (CPET)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria ARM A and ARM B: Histologically-documented localized (stage < T3) prostate adenocarcinoma Patient has selected active surveillance as their management strategy for low- or low-intermediate risk prostate cancer as defined below >= 10 core prostate biopsy completed prior to randomization with Gleason sum =< 6 with no pattern 4, or Gleason 3+4 in < 34% of all cores Diagnostic or most recent prostate specific antigen (PSA) =< 15 ng/ml, or PSA density (PSAD) < 0.15 Low to moderate fitness level at baseline (to be assessed via interview with the exercise staff and through the CPET) Clearance based on medical chart review and normal electrocardiogram (ECG) (administered by a trained health professional) to undergo a symptom-limited cardiopulmonary exercise test and aerobic training intervention Able to achieve and complete an acceptable cardiopulmonary exercise test defined as follows: achieving peak or plateau in oxygen consumption concurrent with increased power output; a respiratory exchange ratio >= 1.1 or volitional exhaustion-rating of perceived exertion > 19 English-speaking A priori, we will allow men with concurrent benign prostatic hyperplasia (prostate volume > 50 g) to have a PSA between 10-15 ng/ml; and include men with low volume Gleason 3+4 disease, because such men have similar outcomes on active surveillance to those with Gleason =< 3+3; also a priori, we will allow men with < than a 10 core biopsy at the discretion of the urologist if s/he classifies the patient as low-risk and a good candidate for active surveillance based on other favorable features (e.g., tumor molecular tests, prostate imaging, etc.) NON-CANCER CONTROL GROUP (EXPLORATORY ARM C): Healthy males age 20-35 or >=60 yrs. No history of prostate cancer or other cancer. Medical clearance based on medical chart review and normal ECG (administered by a trained health professional) to undergo a symptom-limited cardiopulmonary exercise test and aerobic training intervention OR medical clearance based on medical chart review and sub-maximal exercise testing for the remote aerobic training intervention. English-speaking. Low to moderate fitness level at baseline (to be assessed via interview with the exercise staff and through the CPET; similar to Arms A and B); subjects will be frequency-matched to subjects in the prostate cancer exercise intervention group (Arm A) to have a similar distribution of body mass index and facilitate comparisons between these two groups. NON-RANDOMIZED OBSERVATIONAL COMPONENT ELIGIBILITY: Histologically-documented localized (stage < T3) prostate adenocarcinoma. Undergoing or initiating active surveillance. Medical clearance based on medical chart review and normal ECG (administered by a trained health professional) to undergo a symptom-limited cardiopulmonary exercise test and aerobic training intervention. English-speaking. Exclusion Criteria Any prior or concurrent treatment for prostate cancer Use of finasteride or dutasteride within 3 weeks or 6 months, respectively, of study entry Uncontrolled illness, physical disability, or other contraindication to aerobic exercise training including, but not limited to: Acute myocardial Infarction (within 5 days of any planned study procedure) Unstable angina Uncontrolled arrhythmia causing symptoms or hemodynamic compromise Recurrent syncope Active endocarditis Acute myocarditis or pericarditis Symptomatic severe aortic stenosis Uncontrolled heart failure Acute (within 3 months) pulmonary embolus or pulmonary infarction Thrombosis of lower extremities Suspected dissecting aneurysm Uncontrolled asthma Pulmonary edema Room air desaturation at rest =< 85% Respiratory failure Acute non-cardiopulmonary disorders that may affect exercise performance or be aggravated by exercise (ie infection, renal failure, thyrotoxicosis) Mental impairment leading to inability to cooperate NON-RANDOMIZED OBSERVATIONAL AND INTERVENTION COMPONENTS (ARM C): The same exclusion criteria apply as above. Additionally, • Should have no prior history of cancer, except for non-melanoma skin cancer

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Exercise<br>Arm A will engage in up to 4 aerobic sessions per week at 55% to 75% of the individually determined exercise capacity (VO2peak; determined from the cardiopulmonary exercise test (CPET) performed at baseline) for 16 weeks. This exercise prescription will be achieved through   4 sessions / week. Men are provided with a heart rate monitor to help ensure they exercise in their target zone. At baseline & week 16, all patients will complete: (1) lifestyle and quality-of-life questionnaires, (2) measurement of weight (3) collection of research fasting blood sample, (4) collection of urine sample, and (5) cardiorespiratory fitness testing. Archival biopsy tissue samples from before and after the intervention will also be requested. | Behavioral: Exercise<br>* This open-label, two-arm randomized controlled trial (RCT) will investigate the effects of 16 weeks of structured aerobic training, relative to usual care (print material with physical activity guidance) in 76 men with histologically confirmed low-risk prostate adenocarcinoma on active surveillance. The only investigational therapeutic agent being tested in this trial is a behavioral intervention in the form of aerobic training.<br>Other: Cardiopulmonary Exercise Test (CPET)<br>* Exercise capacity test to assess peak oxygen consumption (VO2peak)<br>* Other names: CPET;|
| No Intervention: Arm B: Usual Care<br>Arm B will receive print material with physical activity guidance which includes general physical activity information (e.g., Moving through Cancer - A Guide to Exercise for Cancer Survivors) at baseline, but no specific exercise program or goals. At the conclusion of the 16 weeks, subjects in this group will be provided with a heart rate monitor, an individualized aerobic exercise program based on their cardiorespiratory fitness test results, and opportunity to consult with study exercise physiologist (one-time). | |
| Active Comparator: Arm C: Exploratory<br>Arm C is a non-randomized control group of men without cancer, which will receive all baseline and 16 week follow-up assessments (except tissue procurement) will engage in up to 4 aerobic sessions per week at 55% to 75% of the individually determined exercise capacity (VO2peak; determined from the cardiopulmonary exercise test performed at baseline) for 16 weeks. This exercise prescription will be achieved through   4 sessions / week. Men are provided with a heart rate monitor to help ensure they exercise in their target zone. At baseline & week 16, all patients will complete: (1) lifestyle and quality-of-life questionnaires, (2) measurement of weight (3) collection of research fasting blood sample, (4) collection of urine sample, and (5) cardiorespiratory fitness testing. | Behavioral: Exercise<br>* This open-label, two-arm randomized controlled trial (RCT) will investigate the effects of 16 weeks of structured aerobic training, relative to usual care (print material with physical activity guidance) in 76 men with histologically confirmed low-risk prostate adenocarcinoma on active surveillance. The only investigational therapeutic agent being tested in this trial is a behavioral intervention in the form of aerobic training.<br>Other: Cardiopulmonary Exercise Test (CPET)<br>* Exercise capacity test to assess peak oxygen consumption (VO2peak)<br>* Other names: CPET;|
| Active Comparator: Observational Non-Randomized Group<br>There is also a non-randomized observational component to the study where biospecimens and survey data will be collected and one CPET will be administered. Individuals who will be enrolled to this group include those who do not meet all eligibility criteria for the RCT, or those who do not wish to be in a RCT, but are interested to participate in some lifestyle research. | Other: Cardiopulmonary Exercise Test (CPET)<br>* Exercise capacity test to assess peak oxygen consumption (VO2peak)<br>* Other names: CPET;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cardiopulmonary fitness (Arms A, C, and Observational groups only) | Change in cardiopulmonary fitness as indicated by V02max (from CPET) will be compared across each arm. All analyses will employ the intention-to-treat (ITT) approach. Every attempt will be made to complete the week 16 follow-up assessment on all patients. | Up to 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of aerobic training on general anxiety | Subject will complete the State Trait Anxiety Inventory (STAI) for Adults survey to assess general anxiety scores. The survey measures state and trait anxiety, with 20 questions, and each question can be scored as 1-4 points. Higher scores indicate greater anxiety and the score range is 20-80. | At baseline and 16 weeks, 12 months and 24 months after start of intervention | 
| Effect of aerobic training on specific prostate cancer anxiety | Subjects will complete the Memorial Anxiety Scale for Prostate Cancer (MAXPC) survey to assess specific prostate cancer anxiety. Higher scores indicate greater anxiety and the fear of cancer recurrence score ranges from 0 to 12. | At baseline and 16 weeks, 12 months and 24 months after start of intervention | 
| Adherence to active surveillance | Adherence is measured by the proportion of patients in each study group that remain on active surveillance after 12 months follow-up. | At 12 months | 
| Adherence to active surveillance | Adherence is measured by the proportion of patients in each study group that remain on active surveillance after 24 months follow-up. | At 24 months | 
| Messenger ribonucleic acid (mRNA) expression patterns and prognostic scores in tumor and surrounding stromal (normal) tissue | Effect of aerobic training on mRNA expression patterns using the 1.4 million marker Affymetrix 1.0 Human Exon Array, in formalin-fixed paraffin-embedded (FFPE) prostate biopsy tissue taken before and after the intervention interval.. | At baseline and 16 weeks after start of intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Survey, Active Surveillance, Exercise, Prostate cancer, Life style, Personalized exercise, Exercise trainer