INTense ExeRcise for SurviVAL Among Men with Metastatic Prostate Cancer (INTERVAL - GAP4)

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.