Exercise Prescription Dose for Castration Resistance Prostate Cancer Patients

Study Overview
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Brief Summary
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Recent drug improvement (e.g. abiraterone or enzalutamide) for castration resistant prostate cancer (CRPC) patients has improved survival. As treatment strategies improve and patients live longer, patients must cope with their treatment-induced adverse effects. Improving levels of physical activity (PA) and less amounts of sitting time (e.g. sedentary behavior, SB) could have a positive impact on patient's health, non-cancer mortality, and quality of life and potentially improve survival. The role of PA has not yet been examined in CRPC patients, which is a clear unmet need. No specific PA guidelines exist for CRPC patients, but specific guidelines are warranted because of advanced disease stage, reduced performance score and comorbidity. It is to be expected that the PA level of CRPC patients is lower compared to non-CRPC patients receiving androgen deprivation therapy (ADT). This study aims to determine the optimal starting physical therapy prescription in CRPC patients receiving second line hormone treatment.

Detailed Description
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CRPC patients receiving second-line hormone treatment at Ghent University Hospital are invited to participate in this phase I 3+3 dose escalation design (escalation to next exercise dose per 3 study patients). The prescription start dose is 15min. aerobic training (50-80% maximum heart rate (HRmax). warm-up and cooling-down and 65-80%HRmax. core), 1 set with 8-10 reps. resistance training (50-60% one repetition maximum (1RM), 8 exercises) and 1 set (30s.) with 2 reps. flexibility training (5 exercises). Factors determining compliance for the dose are tolerance and safety. Tolerance for the exercise prescription will be assessed with the Borg scale of perceived exertion after every exercise. Compliant for tolerance is a score ≤16. Safety will be assessed by the visual analogue scale (VAS) (assessed by the patient) for pain and the CTCAE criteria (assessed by a trained health care provider) for bone pain after every exercise. Compliant for safety is ≤3 VAS for exercise-induced pain and <grade 2 according to the CTCAE criteria.

Official Title
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Exercise Prescription Dose for Castration Resistance Prostate Cancer Patients: a Phase I Prescription Dose Escalation Trial

Conditions
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Castration-resistant Prostate Cancer, Prostatic Neoplasms, Exercise, Physical Activity

Intervention / Treatment
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* Behavioral: Exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CRPC patients with second-line hormone treatment Able to walk 400 meters without help from another person Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule (those conditions should be discussed with the patient before registration in the trial) ≥4 weeks since any major surgery and fully recovered before patient registration Written informed consent must be given according to International conference on harmonization Good Clinical Practice and national regulation. Exclusion Criteria: Musculoskeletal, cardiovascular or neurological comorbidity that prevent the patient to participate in an exercise program Painful bone metastases (VAS) at the time of inclusion Unstable bone metastases (SINS classification) at time of inclusion

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: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: phase I study with an exercise prescription as intervention
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single arm phase I trial with 3 exercise dose-escalation arms<br>exercise dose-escalation: aerobic, resistance and flexibility training | Behavioral: Exercise<br>* Exercise according to dose escalation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose based on tolerance | Maximum tolerated dose will be assessed by borg scale of perceived exertion. | change before and after 1 exercise session (at one day) | 
| Maximum tolerated dose based on safety | Maximum tolerated dose will be assessed by CTCAE | change before and after 1 exercise session (at one day) | 
| Maximum tolerated dose based on safety | Maximum tolerated dose will be assessed by VAS | change before and after 1 exercise session (at one day) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functionality | Functionality will be assessed by the Karnofsky Performance Status | baseline | 
| Pain | Pain will be assessed by the Brief pain inventory (BPI) questionnaire | baseline | 
| Health Related quality of Life general | HRQoL will be assessed by the EORTC quality of life (QLQ) C30 questionnaire | baseline | 
| Health Related quality of Life disease specific | HRQoL will be assessed by the EORTC quality of life prostate 25 questionnaire | baseline | 
| Physical activity level by International Physical Activity Questionnaire (IPAQ) | Physical activity level will be assessed by the IPAQ questionnaire | baseline | 
| Physical activity level by Godin | Physical activity level will be assessed by the Godin Leisure questionnaire | baseline | 
| Body composition | Body composition will be assessed by 8-point bioelectrical impedance analysis | baseline | 
| Physical performance | Physical performance will be assessed by the 400m walk test | baseline | 
| Physical performance by time up and go | Physical performance will be assessed by the time up and go test | baseline | 
| Physical performance by 6m walk | Physical performance will be assessed by the 6-meter walk test usual and fast pace | baseline | 
| Physical performance by 6 m walk backward | Physical performance will be assessed by the 6 meter backward walk | baseline | 
| Physical performance by Cardiopulmonary Exercise Testing (CPET) | Physical performance will be assessed by the CPET | baseline | 
| Balance by four square test | Balance will be assessed by the four square test | baseline | 
| Balance by chair rise test | Balance will be assessed by the chair rise test | baseline | 
| Motivation 1 | Motivation will be assessed by the stages of change theory | baseline | 
| Motivation 2 | Motivation will be assessed by the Exercise Motivation Inventory questionnaire | baseline |