Exercise Therapy and Radiation Therapy (EXERT) for Metastatic Prostate Cancer

• ClinicalTrials.gov Identifier: NCT04556045
• Recruitment Status: Not yet recruiting
• First Posted: September 21, 2020
• Last Update Posted: May 3, 2023
• Sponsor: Case Comprehensive Cancer Center
• Information provided by (Responsible Party): Case Comprehensive Cancer Center

Tracking Information

• First Submitted Date: July 28, 2020
• First Posted Date: September 21, 2020
• Last Update Posted Date: May 3, 2023
• Estimated Study Start Date: August 1, 2023
• Estimated Primary Completion Date: January 1, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 14, 2020)

Quality of life using the Patient-Reported Outcomes Measurement Information System (PROMIS Scale v1.2-Global Health) [ Time Frame: At 1 month follow up ]

Patient Reported Outcome Measurement Information System (PROMIS) Global Health v1. 2 short form is a 10-item instrument representing multiple domains. Scores are assigned for both Global Physical Health component and Global Mental Health component. The response scores range from 1-5, where 1 = always and 5 = Never. A higher score from responses indicate better health.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 2, 2022)

• Progression free survival [ Time Frame: Within 5 years ]
  The hypothesis is that adding exercise therapy (ET) to radiation therapy (RT) will improve progression free survival, measured using RECIST criteria
• Overall survival [ Time Frame: Within 5 years ]
  The hypothesis is that adding exercise therapy (ET) to radiation therapy (RT) will improve overall survival, from the date of start of palliative radiotherapy until death.
• Physical Function: Short Physical Performance Battery [ Time Frame: At 1 month follow up ]
  Objectively-measured physical function will be assessed using the Short Physical Performance Battery (SPPB). The SPPB is an accumulation of balance tests, 4-meter gait speed, and 5-chair stands. Based on the time needed to complete the chair stands, a score is given. A summation of scores from all tests is taken, ranging from 0 -12. A higher score = Higher physical function.
• Aerobic Capacity: Six Minute Walk Test [ Time Frame: At 1 month follow up ]
  Objectively-measured physical function will be assessed using the Six Minute Walk Test (6MWT). Distance walked during 6 minutes (measured in meters) is measured. Longer distance = higher aerobic capacity.
• Strength: Hand Grip Strength measured by the grip strength dynamometer test [ Time Frame: At 1 month follow up ]
  Reliable and valid evaluation of hand strength can provide an objective index of general upper body strength. Hand grip strength can be quantified by measuring the amount of static force that the hand can squeeze around a dynamometer. The force is measured in kilograms and/or pounds and corresponds.
• Health-related Quality of Life: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30, version 3.0) [ Time Frame: At 1 month follow up ]
  QoL will be assessed with the validated 30-item self-assessment questionnaire of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30, version 3.0).
• Evaluation of symptomatic toxicity in study participants using the Common Terminology Criteria for Adverse Events- Patient Reported Outcomes (CTCAE-PRO) [ Time Frame: At 1 month follow up ]
  The PRO-CTCAE characterizes the frequency, severity, interference, and presence/absence of symptomatic toxicities that include pain, fatigue, nausea, and cutaneous side effects that can be meaningfully reported from the patient perspective. PRO-CTCAE responses are scored from 0 to 4 (or 0/1 for absent/present) and evaluate the symptom attributes of frequency, severity, interference, amount, presence/absence. Each symptomatic Adverse Event is assessed by 1-3 attributes. Criteria for grading on the CTCAE scale vary by toxicity. Grade 1: asymptomatic or mild symptoms not requiring intervention. Grade 2: moderate symptoms that interfere somewhat with daily function and where some intervention may be indicated. Grade 3: severe symptoms that interfere with daily activities or require more significant intervention. Grade 4: toxicity that is life-threatening, with urgent intervention indicated.
• Godin Physical Activity Questionnaire [ Time Frame: At 1 month follow up ]
  Physical activity behavior in the domains of commuting activity, leisure time activities such as cycling, walking, and sports, household and occupational activity will be assessed via a standardized and validated questionnaire, the Godin Physical Activity Questionnaire. Total weekly leisure activity is calculated in arbitrary units by summing the products of the separate components, as shown in the following formula: Weekly leisure activity score = (9 × Strenuous) + (5 × Moderate) + (3 × Light) Higher activity score = more active
• Fatigue: Fatigue Symptom Inventory [ Time Frame: At 1 month follow up ]
  The Fatigue Symptom Inventory (FSI) assesses the frequency and severity of fatigue as well as its perceived disruptiveness. Frequency is measured as the number of days in the past week (0-7) respondents felt fatigued as well as the percentage of each day on average they felt fatigued (0 = none, 10 = entire day).
• Quantification of IL-1Ra in blood [ Time Frame: At 1 month follow up ]
  A 2-4mL blood sample will be collected to determine participants levels of the biomarker IL-1Ra. Samples will be run via ELISA and concentrations will be reported as pg/mL.

Original Secondary Outcome Measures (submitted: September 14, 2020)

• Progression free survival [ Time Frame: Within 5 years ]
  The hypothesis is that adding exercise therapy (ET) to radiation therapy (RT) will improve progression free survival, measured using RECIST criteria
• Overall survival [ Time Frame: Within 5 years ]
  The hypothesis is that adding exercise therapy (ET) to radiation therapy (RT) will improve overall survival, from the date of start of palliative radiotherapy until death.
• Quantification of IL-1Ra in blood [ Time Frame: At 1 month follow up ]
  A 2-4mL blood sample will be collected to determine participants levels of the biomarker IL-1Ra. Samples will be run via ELISA and concentrations will be reported as pg/mL.
• Physical Function: Short Physical Performance Battery [ Time Frame: At 1 month follow up ]
  Objectively-measured physical function will be assessed using the Short Physical Performance Battery (SPPB). The SPPB is an accumulation of balance tests, 4-meter gait speed, and 5-chair stands. Based on the time needed to complete the chair stands, a score is given. A summation of scores from all tests is taken, ranging from 0 -12. A higher score = Higher physical function.
• Aerobic Capacity: Six Minute Walk Test [ Time Frame: At 1 month follow up ]
  Objectively-measured physical function will be assessed using the Six Minute Walk Test (6MWT). Distance walked during 6 minutes (measured in meters) is measured. Longer distance = higher aerobic capacity.
• Strength: Hand Grip Strength measured by the grip strength dynamometer test [ Time Frame: At 1 month follow up ]
  Reliable and valid evaluation of hand strength can provide an objective index of general upper body strength. Hand grip strength can be quantified by measuring the amount of static force that the hand can squeeze around a dynamometer. The force is measured in kilograms and/or pounds and corresponds.
• Health-related Quality of Life: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30, version 3.0) [ Time Frame: At 1 month follow up ]
  QoL will be assessed with the validated 30-item self-assessment questionnaire of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30, version 3.0).
• Evaluation of symptomatic toxicity in study participants using the Common Terminology Criteria for Adverse Events- Patient Reported Outcomes (CTCAE-PRO) [ Time Frame: At 1 month follow up ]
  The PRO-CTCAE characterizes the frequency, severity, interference, and presence/absence of symptomatic toxicities that include pain, fatigue, nausea, and cutaneous side effects that can be meaningfully reported from the patient perspective. PRO-CTCAE responses are scored from 0 to 4 (or 0/1 for absent/present) and evaluate the symptom attributes of frequency, severity, interference, amount, presence/absence. Each symptomatic Adverse Event is assessed by 1-3 attributes. Criteria for grading on the CTCAE scale vary by toxicity. Grade 1: asymptomatic or mild symptoms not requiring intervention. Grade 2: moderate symptoms that interfere somewhat with daily function and where some intervention may be indicated. Grade 3: severe symptoms that interfere with daily activities or require more significant intervention. Grade 4: toxicity that is life-threatening, with urgent intervention indicated.
• Godin Physical Activity Questionnaire [ Time Frame: At 1 month follow up ]
  Physical activity behavior in the domains of commuting activity, leisure time activities such as cycling, walking, and sports, household and occupational activity will be assessed via a standardized and validated questionnaire, the Godin Physical Activity Questionnaire. Total weekly leisure activity is calculated in arbitrary units by summing the products of the separate components, as shown in the following formula: Weekly leisure activity score = (9 × Strenuous) + (5 × Moderate) + (3 × Light) Higher activity score = more active
• Fatigue: Fatigue Symptom Inventory [ Time Frame: At 1 month follow up ]
  The Fatigue Symptom Inventory (FSI) assesses the frequency and severity of fatigue as well as its perceived disruptiveness. Frequency is measured as the number of days in the past week (0-7) respondents felt fatigued as well as the percentage of each day on average they felt fatigued (0 = none, 10 = entire day).

Current Other Pre-specified Outcome Measures (submitted: September 14, 2020)

• Work Productivity and Activity Impairment Questionnaire [ Time Frame: At 1 month follow up ]
  The Work Productivity and Activity Impairment Questionnaire assesses the effect of patient's health problems on their ability to work and perform regular activities. Subjects self reports as "fill in blank" answers to questions and also as circling a number on a 10 point scale where 0 = Problem had no effect on my work and 10 = Problem completely prevented me from doing my daily activities.
• Barriers to Exercise RM 5-FM [ Time Frame: At 1 month follow up ]
  Examines factors that have an impact on the development and implementation of and adherence to a personal physical activity plan. Questions are scored on a range of 0-3 where, Very Unlikely = 0 and Very Likely = 3. Barriers to physical activity fall into one or more of seven categories: lack of time, social influences, lack of energy, lack of willpower, fear of injury, lack of skill, and lack of resources. A score of 5 or above in any category shows that this is an important barrier to overcome.
• Exploratory pro-inflammatory (IL-1B, IL-6, TNF-α, IL-8, IL-15, CRP) and anti-inflammatory (IL-10) markers [ Time Frame: At 1 month follow up ]
  A 2-4mL blood sample will be collected to determine participants levels of pro- and anti-inflammatory biomarkers.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Exercise Therapy and Radiation Therapy (EXERT) for Metastatic Prostate Cancer
• Official Title: Exercise Therapy and Radiation Therapy (EXERT) for Metastatic Prostate Cancer
• Brief Summary: This study is being done to determine if patients receiving personalized exercise therapy (versus those who do not receive personalized exercise therapy) have improved quality of life and physical functioning after completing their radiation therapy. Second, the study is being done to find if the quality of life changes during therapy correlate with measurements of inflammation in the blood. Third, the study is being done to see if adding exercise therapy to radiation therapy will improve survival.

Detailed Description

In 2018, 30,000 patients were diagnosed metastatic prostate cancer in the US. Short-course radiation therapy (RT) is a mainstay of treatment for symptomatic metastases, and it stimulates an immune response against the tumor. However, RT also decreases systemic interleukin-1 receptor antagonist (IL-1Ra), placing the body in a pro-inflammatory state, and increasing fatigue and reducing quality of life (QOL). Fatigue and QOL are surrogates of the limited 2-20 month survival time. If fatigue and quality of life are improved, then toxicity and survival will follow.

Our long-term goal is to identify the potential for exercise therapy (ET) to improve RT treatment toxicities and outcomes among metastatic cancer patients. The mechanistic hypothesis is that adding ET training to RT decreases long-term systemic inflammation, mitigating toxicity thereby widening the therapeutic window.

Objective 1. Quantify the potential of Exercise Therapy (ET) to mitigate Radiation Treatment (RT) toxicities and physical function decline. The hypothesis is that ET mitigates patient-reported quality of life (QOL) and toxicities of RT. Our approach will be to use standardized questionnaires and assessment tools to assess QOL and physical function.

Objective 2. Characterize the immunologic mechanism by which ET mitigates RT toxicity. The hypothesis is that ET mitigates the toxicity of RT (measured in objective 1) by increasing serum interleukin-1Ra (IL-1Ra).

Objective 3. Evaluate the ability of ET to improve survival. Since physical function is a surrogate of survival, the hypothesis is that adding ET to RT will improve overall survival, measured from the date of start of radiotherapy until death.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Supportive Care
• Condition: Metastatic Prostate Cancer

Intervention

Behavioral: Exercise therapy

The exercise therapy intervention will last 4 weeks. Each participant assigned to this intervention will receive a personalized ET regimen, including in-person, supervised exercise sessions; other activities to be followed at home. Participants will exercise between one and seven times per week depending on their tolerance to the treatment and exercise program.

Study Arms

• Experimental: Radiation Therapy + Exercise Therapy
  This group will receive exercise intervention in addition to their standard of care radiation treatment. At the baseline visit, they will meet with the exercise physiologist and will be provided with a personalized exercise prescription and log to record what they do in between daily radiation treatment visits. The participant will also undergo an in-person exercise session prior to radiation therapy, which will take place either on the same day that the physical function tests are preformed or on a separate day. Participants will exercise between 1 and 7 times/week depending on the patient's tolerance to the exercise prescription. The exercise physiologist will meet with the participant at every radiation treatment visit for an exercise counseling check-in. After five radiation treatments, the exercise physiologist will follow-up with the participants via phone call once per week for 4 weeks during the follow-up period.
  Intervention: Behavioral: Exercise therapy
• No Intervention: Radiation Therapy
  The observational group will continue with their usual standard of care of radiation therapy. The study team will provide patients with an educational pamphlet at the end of their baseline visit. They will also be provided with "Moving Through Cancer: A Guide to Exercise for Cancer Survivors" framework. Additionally, the participant's medical record will be reviewed for serious adverse events during their time on study. Baseline and final measurements will be obtained.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: September 14, 2020): 80
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 1, 2026
• Estimated Primary Completion Date: January 1, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Males ≥18 years of age receiving first palliative course of RT for metastatic prostate cancer
• Patient receiving radiation dose of 20 Gray (Gy) in 5 fractions or stereotactic body radiation therapy (SBRT)
• Patient must have received prior hormone therapy. Use of prior chemotherapy agents is allowed, but not necessary.
• Fluent in written and spoken English
• Must be able to provide and understand informed consent
• Must have an ECOG Performance Status (PS) of ≤ 3
• Scheduled to receive radiation therapy at University Hospitals Cleveland Medical Center or University Hospitals Lake Health Center
• Primary attending radiation oncologist approval

Exclusion Criteria:

• Receiving radiation therapy at a location other than University Hospitals Cleveland Medical Center or University Hospitals Lake Health Center
• Performing > 90 minutes/week of exercise therapy prior at time of enrollment
• Evidence in the medical record of an absolute contraindication for exercise
• Cardiac exclusion criteria:
• Class II, III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system
• History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty or stenting within the past 6 months prior to the start of radiation therapy
• Uncontrolled arrhythmias; patients with rate-controlled atrial fibrillation for >1 month prior to start of radiation therapy may be eligible
• syncope
• acute myocarditis, pericarditis, or endocarditis
• acute pulmonary embolus or pulmonary infarction
• thrombosis of lower extremities
• suspected dissecting aneurysm
• pulmonary edema
• respiratory failure
• acute non-cardiopulmonary disorder that may affect exercise performance or be aggravated by exercise
• Mental impairment leading to inability to complete study requirements
• In-patient receiving radiation therapy for a radiation emergency (e.g. cord compression, Superior vena cava (SVC) syndrome, brain metastases)
• High risk of fracture or spine instability (Mirels score ≥7, SINS ≥7)
• Children (the protocol will only include men age 18 and older)

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Nicholas G Zaorsky, MD, MS; 1-800-641-2422; CTUReferral@UHhospitals.org

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04556045
• Other Study ID Numbers: CASE8821
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Plan to share all collected data relevant to results in publication.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: Analytic Code

• Current Responsible Party: Case Comprehensive Cancer Center
• Original Responsible Party: Nicholas Zaorsky, Milton S. Hershey Medical Center, Assistant Professor, Department of Radiation Oncology
• Current Study Sponsor: Case Comprehensive Cancer Center
• Original Study Sponsor: Milton S. Hershey Medical Center
• Collaborators: Not Provided

Investigators

• Principal Investigator: Nicholas Zaorsky, MD; University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

• PRS Account: Case Comprehensive Cancer Center
• Verification Date: May 2023