Clinical trial NCT02730338: INTense ExeRcise for SurviVAL Among Men with Metastatic Prostate Cancer (INTERVAL - GAP4)
Official title: INTense ExeRcise for SurviVAL Among Men with Metastatic Prostate Cancer (INTERVAL - GAP4): a Multicentre, Randomised, Controlled, Phase III Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Metastatic Prostate Cancer
Keywords: Castrate resistant
Exercise
Metastatic
Prostate cancer
Hormone sensitive
Lead sponsor: Movember Foundation
Sponsor class: OTHER
Collaborators: name: University of California, San Francisco
name: Edith Cowan University
name: King's College London
name: Centre hospitalier de l'Université de Montréal (CHUM)
First posted: 2016-04-06
Enrollment: 866
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To determine if supervised high intensity aerobic and resistance training increases overall survival compared to self-directed exercise in patients with metastatic prostate cancer.


Eligibility criteria: Inclusion Criteria:

mCRPC status:

* mCRPC patients defined as; adenocarcinoma of the prostate with systemic metastatic disease despite castrate levels of testosterone (\<50 ng/dL) due to orchiectomy or LHRH agonist.

  o Patients must have one or more of the following to be considered mCRPC
* Metastatic Disease Progression: \>20% increase in the sum of diameters of measurable lesions from the time of maximal regression or appearance of one or more new lesions.
* Bone Scan Progression: Appearance of one or more new lesions on bone scan attributable to prostate cancer.
* PSA Progression: PSA ≥2 ng/ml that has risen serially on at least two occasions, each at least one week apart (PSA1 \< PSA2 \< PSA3).
* PSMA PET/CT scan progression: Appearance of one or more new lesions on PSMA PET/CT scan attributable to prostate cancer.
* At enrolment, mCRPC patients must fit into one of the following 5 categories:

  1. Treatment naïve for mCRPC (have not yet started approved therapies for CRPC ie: Abiraterone/Enzalutamide/Apalutamide / or Docetaxel, Cabazitaxel or other approved first line chemotherapy; less than 4 weeks on approved therapies is still considered to be treatment naïve) Or
  2. Receiving Abi/Enza/Apa for mCRPC AND responding or stable (PSA values must be stable or declining after at least 4 weeks since starting Abi/Enza/Apa for mCRPC) Or
  3. Patients with PSA progression while on Abi/Enza/Apa are eligible as long as they are asymptomatic AND there is no intent on starting chemotherapy within 6 months Or
  4. Patients treated with Docetaxel, Cabazitaxel or other approved first line chemotherapy as first line for mCRPC who are asymptomatic without ANY evidence of progression Or
  5. Patients may have progressed following first line Docetaxel, Cabazitaxel or other first line chemotherapy and are now receiving treatment with Abi/Enza/Apa. These patients must absolutely be responding or stable (PSA values must be stable or declining after starting Abi/Enza/Apa treatment) and have an estimated life expectancy of more than 1 year.

     mHSPC Status:
* mHSPC patients must be classified as either high-risk or high-volume mHSPC. These groups are defined as adenocarcinoma of the prostate with systemic metastatic disease and patients also fit into one of the following 2 categories: 6. High-risk: defined as having at least 2 of three criteria: (i) Gleason score ≥8, (ii) presence of ≥3 lesions on bone scan, or (iii) presence of INTERVAL Protocol Version 5.0, 19 August 2019 4 measurable visceral lesions (PSMA PET imaging should not be used in the definition of high-risk disease) Or 7. High-volume: defined as having the presence of visceral metastases and/or ≥ four bone metastases with at least one outside of the vertebral column and pelvis (PSMA PET imaging should not be used in the definition of high-volume disease)

Additional criteria for all groups:

* All patients will be required to be on ADT during the study period or have had a prior bilateral orchiectomy.
* Men with small cell neuroendocrine tumours or features of small cell disease are not eligible.
* ≥4 weeks since last major surgery and fully recovered.
* No known contraindications to high intensity exercise, including, but not limited to: brain metastases; current congestive heart failure (New York Heart Association Class II, III or IV); serious or non-healing wound, ulcer, or bone fracture; spinal cord compromise or instrumentation due to metastatic disease; peripheral neuropathy ≥grade 3. No serious cardiovascular events within 12 months including, but not limited to, transient ischemic attack (TIA), cerebrovascular accident (CVA), or myocardial infarction (MI). Patients with a history of hypertension must be well-controlled (\< 160/90) on anti-hypertensive therapy.
* Halabi Nomogram score \<1951 (Risk Category rated as low or intermediate risk)
* Age ≥18 years
* Required Baseline Laboratory Values: ANC ≥ 1500/uL; Platelet count ≥ 100,000/uL; Creatinine ≤ 1.5 x upper limits of normal; Bilirubin ≤ 1.5 x upper limits of normal; AST ≤ 1.5 x upper limits of normal; Serum testosterone ≤ 50 ng/dL
* ECOG performance status 0-1
* Medical clearance by treating physician to undergo a symptom-limited cardiopulmonary exercise test and vigorous aerobic and resistance exercise training, and able to complete an acceptable cardiopulmonary exercise test.
* Exercise Coordination Centre (ECC) review and approval of subject's screening bone scan / areas with bone metastases.
* Men participating in vigorous aerobic exercise for \>60 min/week or structured resistance exercise ≥2 days/week, are not eligible.
* Subject is willing and able to use technological aspects of the trial.
* The subject is fluent in the language as designated by the institution at which he would be enrolled.

Primary outcomes:
measure: Overall Survival
timeFrame: up to 5 years
Secondary outcomes:
measure: Disease Progression
timeFrame: up to 5 years
measure: Symptomatic Skeletal Related Events (SSE)
timeFrame: up to 5 years
measure: Opiate Use
timeFrame: up to 5 years
measure: Analgesic Use
timeFrame: up to 5 years
measure: Biomarker analysis
timeFrame: up to 5 years
measure: Biomarker analysis
timeFrame: up to 5 years
measure: Biomarker analysis
timeFrame: up to 5 years
measure: Quality of Life
timeFrame: up to 5 years
measure: Physical Function
timeFrame: up to 5 years
measure: Pain
timeFrame: up to 5 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Centre
state: California
city: San Francisco
country: United States
facility: UCSF
state: California
city: Denver
country: United States
facility: UC Denver
state: Colorado
city: Mineapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Centre
state: Washington
city: Brisbane
country: Australia
facility: Australian Prostate Cncr Research Centre
state: Queensland
city: Brisbane
country: Australia
facility: University of Queensland
state: Queensland
city: Melbourne
country: Australia
facility: Victoria University / Sunshine Hospital
state: Victoria
city: Perth
country: Australia
facility: Edith Cowan University
state: Western Australia
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal (CRCHUM)
city: Cologne
country: Germany
facility: German Sport University Cologne
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Guildford
country: United Kingdom
facility: University of Surrey
state: Surrey
city: Belfast
country: United Kingdom
facility: Queen's University Belfast
city: Glasgow
country: United Kingdom
facility: University of Glasgow
city: London
country: United Kingdom
facility: Kings College London
Study officials:
affiliation: Edith Cowan University
name: Robert Newton
role: STUDY_CHAIR
affiliation: Centre hospitalier de l'Université de Montréal (CHUM)
name: Fred Saad
role: STUDY_CHAIR
References:
citation: 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, Galvao DA, Ryan CJ, Saad F. Intense Exercise for Survival among Men with Metastatic Castrate-Resistant Prostate Cancer (INTERVAL-GAP4): a multicentre, randomised, controlled phase III study protocol. BMJ Open. 2018 May 14;8(5):e022899. doi: 10.1136/bmjopen-2018-022899.