Intense Exercise for Survival among Men with Metastatic Castrate-Resistant Prostate Cancer (INTERVAL-GAP4)

A multicentre, randomised, controlled phase III study protocol

Robert U. Newton, Stacey A. Kenfield, Nicolas H. Hart, June M. Chan, Kerry S. Courneya, James Catto, Stephen P. Finn, Rosemary Greenwood, Daniel C. Hughes, Lorelei Mucci, Stephen R. Plymate, Stephan F.E. Praet, Emer M. Guinan, Erin L. Van Blarigan, Orla Casey, Mark Buzza, Sam Gledhill, Li Zhang, Daniel A. Galvão, Charles J. Ryan & 1 others Fred Saad

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Abstract

Introduction: Preliminary evidence supports the beneficial role of physical activity on prostate cancer outcomes. This phase III randomised controlled trial (RCT) is designed to determine if supervised high-intensity aerobic and resistance exercise increases overall survival (OS) in patients with metastatic castrate-resistant prostate cancer (mCRPC). Methods and analysis: Participants (n=866) must have histologically documented metastatic prostate cancer with evidence of progressive disease on androgen deprivation therapy (defined as mCRPC). Patients can be treatment-naïve for mCRPC or on first-line androgen receptor-targeted therapy for mCRPC (ie, abiraterone or enzalutamide) without evidence of progression at enrolment, and with no prior chemotherapy for mCRPC. Patients will receive psychosocial support and will be randomly assigned (1:1) to either supervised exercise (high-intensity aerobic and resistance training) or self-directed exercise (provision of guidelines), stratified by treatment status and site. Exercise prescriptions will be tailored to each participant's fitness and morbidities. The primary endpoint is OS. Secondary endpoints include time to disease progression, occurrence of a skeletal-related event or progression of pain, and degree of pain, opiate use, physical and emotional quality of life, and changes in metabolic biomarkers. An assessment of whether immune function, inflammation, dysregulation of insulin and energy metabolism, and androgen biomarkers are associated with OS will be performed, and whether they mediate the primary association between exercise and OS will also be investigated. This study will also establish a biobank for future biomarker discovery or validation. Ethics and dissemination: Validation of exercise as medicine and its mechanisms of action will create evidence to change clinical practice. Accordingly, outcomes of this RCT will be published in international, peer-reviewed journals, and presented at national and international conferences. Ethics approval was first obtained at Edith Cowan University (ID: 13236 Newton), with a further 10 investigator sites since receiving ethics approval, prior to activation.

Original languageEnglish
Article number022899
Pages (from-to)1-15
Number of pages15
JournalBMJ Open
Volume8
DOIs
Publication statusPublished - May 2018

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Prostatic Neoplasms
Exercise
Survival
Ethics
Biomarkers
Androgens
Opiate Alkaloids
Randomized Controlled Trials
Pain
Resistance Training
Androgen Receptors
Therapeutics
Energy Metabolism
Prescriptions
Disease Progression
Quality of Life
Research Personnel
Medicine
Guidelines
Insulin

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Newton, Robert U. ; Kenfield, Stacey A. ; Hart, Nicolas H. ; Chan, June M. ; Courneya, Kerry S. ; Catto, James ; Finn, Stephen P. ; Greenwood, Rosemary ; Hughes, Daniel C. ; Mucci, Lorelei ; Plymate, Stephen R. ; Praet, Stephan F.E. ; Guinan, Emer M. ; Van Blarigan, Erin L. ; Casey, Orla ; Buzza, Mark ; Gledhill, Sam ; Zhang, Li ; Galvão, Daniel A. ; Ryan, Charles J. ; Saad, Fred. / Intense Exercise for Survival among Men with Metastatic Castrate-Resistant Prostate Cancer (INTERVAL-GAP4) : A multicentre, randomised, controlled phase III study protocol. In: BMJ Open. 2018 ; Vol. 8. pp. 1-15.
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abstract = "Introduction: Preliminary evidence supports the beneficial role of physical activity on prostate cancer outcomes. This phase III randomised controlled trial (RCT) is designed to determine if supervised high-intensity aerobic and resistance exercise increases overall survival (OS) in patients with metastatic castrate-resistant prostate cancer (mCRPC). Methods and analysis: Participants (n=866) must have histologically documented metastatic prostate cancer with evidence of progressive disease on androgen deprivation therapy (defined as mCRPC). Patients can be treatment-na{\"i}ve for mCRPC or on first-line androgen receptor-targeted therapy for mCRPC (ie, abiraterone or enzalutamide) without evidence of progression at enrolment, and with no prior chemotherapy for mCRPC. Patients will receive psychosocial support and will be randomly assigned (1:1) to either supervised exercise (high-intensity aerobic and resistance training) or self-directed exercise (provision of guidelines), stratified by treatment status and site. Exercise prescriptions will be tailored to each participant's fitness and morbidities. The primary endpoint is OS. Secondary endpoints include time to disease progression, occurrence of a skeletal-related event or progression of pain, and degree of pain, opiate use, physical and emotional quality of life, and changes in metabolic biomarkers. An assessment of whether immune function, inflammation, dysregulation of insulin and energy metabolism, and androgen biomarkers are associated with OS will be performed, and whether they mediate the primary association between exercise and OS will also be investigated. This study will also establish a biobank for future biomarker discovery or validation. Ethics and dissemination: Validation of exercise as medicine and its mechanisms of action will create evidence to change clinical practice. Accordingly, outcomes of this RCT will be published in international, peer-reviewed journals, and presented at national and international conferences. Ethics approval was first obtained at Edith Cowan University (ID: 13236 Newton), with a further 10 investigator sites since receiving ethics approval, prior to activation.",
keywords = "disease progression, immune function, inflammation, physical activity, tumour biology",
author = "Newton, {Robert U.} and Kenfield, {Stacey A.} and Hart, {Nicolas H.} and Chan, {June M.} and Courneya, {Kerry S.} and James Catto and Finn, {Stephen P.} and Rosemary Greenwood and Hughes, {Daniel C.} and Lorelei Mucci and Plymate, {Stephen R.} and Praet, {Stephan F.E.} and Guinan, {Emer M.} and {Van Blarigan}, {Erin L.} and Orla Casey and Mark Buzza and Sam Gledhill and Li Zhang and Galv{\~a}o, {Daniel A.} and Ryan, {Charles J.} and Fred Saad",
year = "2018",
month = "5",
doi = "10.1136/bmjopen-2018-022899",
language = "English",
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pages = "1--15",
journal = "BMJ Open",
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Newton, RU, Kenfield, SA, Hart, NH, Chan, JM, Courneya, KS, Catto, J, Finn, SP, Greenwood, R, Hughes, DC, Mucci, L, Plymate, SR, Praet, SFE, Guinan, EM, Van Blarigan, EL, Casey, O, Buzza, M, Gledhill, S, Zhang, L, Galvão, DA, Ryan, CJ & Saad, F 2018, 'Intense Exercise for Survival among Men with Metastatic Castrate-Resistant Prostate Cancer (INTERVAL-GAP4): A multicentre, randomised, controlled phase III study protocol', BMJ Open, vol. 8, 022899, pp. 1-15. https://doi.org/10.1136/bmjopen-2018-022899

Intense Exercise for Survival among Men with Metastatic Castrate-Resistant Prostate Cancer (INTERVAL-GAP4) : A multicentre, randomised, controlled phase III study protocol. / Newton, Robert U.; Kenfield, Stacey A.; Hart, Nicolas H.; Chan, June M.; Courneya, Kerry S.; Catto, James; Finn, Stephen P.; Greenwood, Rosemary; Hughes, Daniel C.; Mucci, Lorelei; Plymate, Stephen R.; Praet, Stephan F.E.; Guinan, Emer M.; Van Blarigan, Erin L.; Casey, Orla; Buzza, Mark; Gledhill, Sam; Zhang, Li; Galvão, Daniel A.; Ryan, Charles J.; Saad, Fred.

In: BMJ Open, Vol. 8, 022899, 05.2018, p. 1-15.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Intense Exercise for Survival among Men with Metastatic Castrate-Resistant Prostate Cancer (INTERVAL-GAP4)

T2 - A multicentre, randomised, controlled phase III study protocol

AU - Newton, Robert U.

AU - Kenfield, Stacey A.

AU - Hart, Nicolas H.

AU - Chan, June M.

AU - Courneya, Kerry S.

AU - Catto, James

AU - Finn, Stephen P.

AU - Greenwood, Rosemary

AU - Hughes, Daniel C.

AU - Mucci, Lorelei

AU - Plymate, Stephen R.

AU - Praet, Stephan F.E.

AU - Guinan, Emer M.

AU - Van Blarigan, Erin L.

AU - Casey, Orla

AU - Buzza, Mark

AU - Gledhill, Sam

AU - Zhang, Li

AU - Galvão, Daniel A.

AU - Ryan, Charles J.

AU - Saad, Fred

PY - 2018/5

Y1 - 2018/5

N2 - Introduction: Preliminary evidence supports the beneficial role of physical activity on prostate cancer outcomes. This phase III randomised controlled trial (RCT) is designed to determine if supervised high-intensity aerobic and resistance exercise increases overall survival (OS) in patients with metastatic castrate-resistant prostate cancer (mCRPC). Methods and analysis: Participants (n=866) must have histologically documented metastatic prostate cancer with evidence of progressive disease on androgen deprivation therapy (defined as mCRPC). Patients can be treatment-naïve for mCRPC or on first-line androgen receptor-targeted therapy for mCRPC (ie, abiraterone or enzalutamide) without evidence of progression at enrolment, and with no prior chemotherapy for mCRPC. Patients will receive psychosocial support and will be randomly assigned (1:1) to either supervised exercise (high-intensity aerobic and resistance training) or self-directed exercise (provision of guidelines), stratified by treatment status and site. Exercise prescriptions will be tailored to each participant's fitness and morbidities. The primary endpoint is OS. Secondary endpoints include time to disease progression, occurrence of a skeletal-related event or progression of pain, and degree of pain, opiate use, physical and emotional quality of life, and changes in metabolic biomarkers. An assessment of whether immune function, inflammation, dysregulation of insulin and energy metabolism, and androgen biomarkers are associated with OS will be performed, and whether they mediate the primary association between exercise and OS will also be investigated. This study will also establish a biobank for future biomarker discovery or validation. Ethics and dissemination: Validation of exercise as medicine and its mechanisms of action will create evidence to change clinical practice. Accordingly, outcomes of this RCT will be published in international, peer-reviewed journals, and presented at national and international conferences. Ethics approval was first obtained at Edith Cowan University (ID: 13236 Newton), with a further 10 investigator sites since receiving ethics approval, prior to activation.

AB - Introduction: Preliminary evidence supports the beneficial role of physical activity on prostate cancer outcomes. This phase III randomised controlled trial (RCT) is designed to determine if supervised high-intensity aerobic and resistance exercise increases overall survival (OS) in patients with metastatic castrate-resistant prostate cancer (mCRPC). Methods and analysis: Participants (n=866) must have histologically documented metastatic prostate cancer with evidence of progressive disease on androgen deprivation therapy (defined as mCRPC). Patients can be treatment-naïve for mCRPC or on first-line androgen receptor-targeted therapy for mCRPC (ie, abiraterone or enzalutamide) without evidence of progression at enrolment, and with no prior chemotherapy for mCRPC. Patients will receive psychosocial support and will be randomly assigned (1:1) to either supervised exercise (high-intensity aerobic and resistance training) or self-directed exercise (provision of guidelines), stratified by treatment status and site. Exercise prescriptions will be tailored to each participant's fitness and morbidities. The primary endpoint is OS. Secondary endpoints include time to disease progression, occurrence of a skeletal-related event or progression of pain, and degree of pain, opiate use, physical and emotional quality of life, and changes in metabolic biomarkers. An assessment of whether immune function, inflammation, dysregulation of insulin and energy metabolism, and androgen biomarkers are associated with OS will be performed, and whether they mediate the primary association between exercise and OS will also be investigated. This study will also establish a biobank for future biomarker discovery or validation. Ethics and dissemination: Validation of exercise as medicine and its mechanisms of action will create evidence to change clinical practice. Accordingly, outcomes of this RCT will be published in international, peer-reviewed journals, and presented at national and international conferences. Ethics approval was first obtained at Edith Cowan University (ID: 13236 Newton), with a further 10 investigator sites since receiving ethics approval, prior to activation.

KW - disease progression

KW - immune function

KW - inflammation

KW - physical activity

KW - tumour biology

UR - http://www.scopus.com/inward/record.url?scp=85053129281&partnerID=8YFLogxK

U2 - 10.1136/bmjopen-2018-022899

DO - 10.1136/bmjopen-2018-022899

M3 - Article

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SN - 2044-6055

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