INTense ExeRcise for surviVAL Among Men With Metastatic Prostate Cancer (INTERVAL - GAP4)
INTense ExeRcise for surviVAL Among Men With Metastatic Prostate Cancer (INTERVAL - GAP4)
To determine if supervised high intensity aerobic and resistance training increases overall
 survival compared to self-directed exercise in patients with metastatic prostate cancer.
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.