Eligibility Details:
Inclusion Criteria:
Patients must be mCRPC. This is defined as adenocarcinoma of the prostate with systemic
metastatic disease despite castrate levels of testosterone (<50 ng/dL) due to orchiectomy
or LHRH agonist.
- 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).
- Castrate levels of testosterone must be maintained while on study. Be on androgen
deprivation therapy (ADT) with a GnRH agonist/antagonist or prior bilateral
orchiectomy. 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.
At enrolment, 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/Docetaxel; 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 as first line therapy for mCRPC who are asymptomatic
without ANY evidence of progression Or
5. Patients may have progressed following Docetaxel first line 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 expected life expectancy of more than 1 year.
- ≥4 weeks since any major surgery and fully recovered.
- Halabi Nomogram score <1951
- Age ≥18 years
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Patients must be able to travel to one of the study-designated exercise
facilities up to three days per week for four weeks during cycle 0, two days per
week for cycles 1-8 (32 weeks) and once per week for cycles 9-11 (12 weeks). In
addition, patients must be able to attend exercise testing visits as outlined in
the Table 1.Required Initial Laboratory Values:
- Absolute neutrophil count (ANC) ≥ 1500/uL
- Platelet count ≥ 100,000/uL
- Creatinine ≤ 1.5 x upper limits of normal
- Bilirubin ≤ 1.5 x upper limits of normal
- Aspartate aminotransferase (AST) ≤ 1.5 x upper limits of normal
- PSA ≥ 2 ng/ml
- Serum testosterone ≤ 50 ng/dL
- Medical clearance to undergo a symptom-limited cardiopulmonary exercise test
(CPET) and vigorous aerobic and resistance exercise training.
o Appendix 8: Patients must answer 'No' to all questions. If patients answered
'Yes' to only Questions 8-11, they will be considered eligible upon physician
clearance
- Successfully pass the screening CPET by achieving:
o Volitional exhaustion (RPE ≥ 9 using the 0-10 RPE scale) after 8 (or more)
minutes, in the absence of any cardiorespiratory abnormalities.
- If cardiorespiratory abnormalities are identified, please refer the patient to
his managing physician for further assessment and diagnosis.
- Note: To assist practitioners with delivering valid CPET assessments, patients
nearing exhaustion should achieve a respiratory exchange ratio (RER) of ≥1.1.
- RER is not a criteria of the test. This objective measure should only be used to
assist practitioners with patient management and decision-making.
- Exercise Coordination Centre (ECC) review and approval of subject's screening
bone scan/ areas with bone metastases.
- Subject is willing and able to use the technological aspects of the trial.
- The subject is fluent in the language as designated by the institution at which
he would be enrolled.
Exclusion Criteria:
- Previous progression (radiographic or PSA progression) while on treatment with
abiraterone, enzalutamide, or a combination.
- Previously identified small cell neuroendocrine tumours or pure small cell carcinoma
of the prostate, based on a prior biopsy of the prostate.
- Brain metastases (brain imaging is not required)
- Any prior chemotherapy for castration-resistant disease is not allowed. Previous
and/or concurrent treatment with other anti-cancer treatments is permitted. Patients
are allowed to be treated with chemotherapy during the duration of the trial. Patients
who have received chemotherapy as part of initial androgen deprivation therapy for
metastatic castration sensitive disease are eligible.
- Currently receiving experimental treatment with non-approved drugs at the time of
enrolment. Patients must undergo a 28-day washout between last dose and screening
CPET.
- Poorly controlled hypertension. During screening ≥2/3 of readings must be < 160/90,
regardless of whether on a regimen of anti-hypertensive therapy or not.
- Current congestive heart failure (New York Heart Association Class II, III or IV)
- Recent serious cardiovascular events (within 12 months) including, but not limited to,
transient ischemic attack (TIA), cerebrovascular accident (CVA), or myocardial
infarction (MI).
- Medical condition such as uncontrolled infection or cardiac disease that, in the
opinion of the physician, would make this protocol unreasonably hazardous for the
patient (see Section 4.4-4.10).
- Patients with a currently active second malignancy other than non-melanoma skin
cancer. Patients are not considered to have a currently active malignancy if they have
completed necessary therapy and are considered by their physician to be at <30% risk
of relapse at time of assessment.
- Psychiatric illness, which would prevent the patient from giving informed consent or
adhering to the study protocol.
- Serious or non-healing wound, ulcer, or bone fracture.
- Known spinal cord compromise or instrumentation due to metastatic disease. Radiation
therapy for metastatic disease is allowed.
- Peripheral neuropathy ≥grade 3.
- Men participating in vigorous aerobic exercise for more than 60 minutes per week or
resistance exercise two or more days per week
- Experiences shortness of breath, chest discomfort, or palpitations when performing
activities of daily living
- Has difficulty climbing a flight of stairs or walking eight blocks due to physical
impairment
- Ongoing restriction of physical activity with physician documentation
- Has chest pain brought on by physical activity
- Has developed chest pain in the past month
- Moderate-to-severe bone pain (i.e., National Cancer Institute's Common Terminology
Criteria for Adverse Events grade 2-3 bone pain).
- Men who do not complete the baseline lifestyle and quality-of-life questionnaires and
3-days of diet diaries or Food Frequency Questionnaire (FFQ) (TBD) will not be
eligible
common.study.methods.has-drugs-no
common.study.methods.is-healthy-no
