INTense Exercise foR surVivAL Among Men With Metastatic Castrate-Resistant Prostate Cancer


Condition: Prostate Cancer Metastatic

Intervention:

  • Behavioral: High intensity aerobic and resistance training
  • Behavioral: Psychosocial support

Purpose: A study to determine if high intensity aerobic and resistance training (Supervised Exercise) plus psychosocial support increases overall survival compared to psychosocial support alone (Self-directed Exercise) in patients with metastatic castrate-resistant prostate cancer.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02730338

Sponsor: Movember Foundation

Primary Outcome Measures:

  • Measure: Overall Survival
  • Time Frame: up to 5 years
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Disease Progression
  • Time Frame: up to 5 years
  • Safety Issue:
  • Measure: Symptomatic Skeletal Related Events (SSE)
  • Time Frame: up to 5 years
  • Safety Issue:
  • Measure: Opiate Use
  • Time Frame: up to 5 years
  • Safety Issue:
  • Measure: Analgesic Use
  • Time Frame: up to 5 years
  • Safety Issue:
  • Measure: Biomarker analysis
  • Time Frame: up to 5 years
  • Safety Issue:
  • Measure: Biomarker analysis
  • Time Frame: up to 5 years
  • Safety Issue:
  • Measure: Biomarker analysis
  • Time Frame: up to 5 years
  • Safety Issue:
  • Measure: Quality of Life
  • Time Frame: up to 5 years
  • Safety Issue:
  • Measure: Physical Function
  • Time Frame: up to 5 years
  • Safety Issue:
  • Measure: Pain
  • Time Frame: up to 5 years
  • Safety Issue:

Estimated Enrollment: 866

Study Start Date: January 2016

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: Male

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

Contact:

  • Anthony Treacy
  • +61 (0)412872510

Locations:

  • Cedars Sinai Medical Centre
  • Los Angeles California United States
  • UCSF
  • San Francisco California United States
  • UC Denver
  • Denver Colorado United States
  • University of Minnesota
  • Minneapolis Minnesota United States
  • Oregon Health & Science University
  • Portland Oregon United States
  • Fred Hutchinson Cancer Centre
  • Seattle Washington United States
  • Australian Prostate Cncr Research Centre
  • Brisbane Queensland Australia
  • GenesisCare Wesley
  • Brisbane Queensland Australia
  • University of Queensland
  • Brisbane Queensland Australia
  • Epworth Hospital
  • Melbourne Victoria Australia
  • Victoria University / Sunshine Hospital
  • Melbourne Victoria Australia
  • Edith Cowan University
  • Perth Western Australia Australia
  • University of Alberta
  • Edmonton Alberta Canada
  • QEII Cancer Centre / Dalhousie University
  • Halifax Nova Scotia Canada
  • Princess Margaret Cancer Centre
  • Toronto Ontario Canada
  • Centre Hospitalier de l'Université de Montréal (CRCHUM)
  • Montreal Canada
  • West China Hospital of Sichuan University
  • Chengdu China
  • German Sport University Cologne
  • Cologne Germany
  • Trinity University
  • Dublin Ireland
  • Erasmus MC
  • Rotterdam Netherlands
  • University of Surrey
  • Guildford Surrey United Kingdom
  • University of Bath / Bath Royal United Hospital
  • Bath United Kingdom
  • Queen's University Belfast
  • Belfast United Kingdom
  • University of Glasgow
  • Glasgow United Kingdom
  • Kings College London
  • London United Kingdom

View trial on ClinicalTrials.gov


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