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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02730338
Recruitment Status : Recruiting
First Posted : April 6, 2016
Last Update Posted : June 28, 2019
Sponsor:
Collaborators:
University of California, San Francisco
Edith Cowan University
King's College London
Centre hospitalier de l'Université de Montréal (CHUM)
Epworth Foundation
Information provided by (Responsible Party):
Movember Foundation

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Metastatic Behavioral: High intensity aerobic and resistance training Behavioral: Psychosocial support Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 866 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: INTense Exercise foR surVivAL Among Men With Metastatic Castrate-Resistant Prostate Cancer
Actual Study Start Date : January 2016
Estimated Primary Completion Date : October 2024
Estimated Study Completion Date : October 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Arm A: Supervised exercise group
Supervised high intensity aerobic and resistance exercise tapering to self management with psychosocial support
Behavioral: High intensity aerobic and resistance training
Behavioral: Psychosocial support
Arm B: Self directed exercise group
Self directed exercise and psychosocial support group
Behavioral: Psychosocial support



Primary Outcome Measures :
  1. Overall Survival [ Time Frame: up to 5 years ]
    Overall survival will be measured from the time of randomization until death


Secondary Outcome Measures :
  1. Disease Progression [ Time Frame: up to 5 years ]
    Time to disease progression will be measured from randomization until the first of the following: first CT or bone scan documenting disease progression, initiation of a new therapy for MCRPC (clinical progression), or first occurrence of a Symptomatic Skeletal Related Event (SSE).

  2. Symptomatic Skeletal Related Events (SSE) [ Time Frame: up to 5 years ]

    Time to first occurrence of SSE will be defined as the time from randomization to documentation of any of the following (whichever occurs first) + 1 day:

    • Use of external beam radiation therapy to relieve bone pain
    • Occurrence of new symptomatic pathological bone fractures that may be vertebral or non-vertebral. Asymptomatic compression fractures detected by radiology review only will not be considered a SSE.
    • Spinal cord compression
    • Change in antineoplastic therapy to treat bone pain
    • Surgical intervention to treat bone pain

  3. Opiate Use [ Time Frame: up to 5 years ]
    Opiate use will be assessed via BPI-SF, the medical record review at entry with a lead-in period (<28 days). The questionnaires will be administered every three cycles until month 24, and in month 36.

  4. Analgesic Use [ Time Frame: up to 5 years ]
    Analgesic use will be assessed via BPI-SF, the World Health Organisation (WHO) analgesic scale, and medical record review at entry with a lead-in period (<28 days). The WHO analgesic scale will be completed every three cycles (based on medical review) and questionnaires will be administered every three cycles until month 24, and in month 36.

  5. Biomarker analysis [ Time Frame: up to 5 years ]
    Inflammatory and cytokine systemic milieu

  6. Biomarker analysis [ Time Frame: up to 5 years ]
    Insulin/Glucose Metabolism

  7. Biomarker analysis [ Time Frame: up to 5 years ]
    Androgen biosynthesis

  8. Quality of Life [ Time Frame: up to 5 years ]
    Physical and emotional quality of life measured by the questionnaires- Functional Assessment of Cancer Therapy- Prostate (FACT-P), Functional assessment of Chronic Illness Therapy (FACIT-Fatigue), and EuroQOL Five Dimension Questionnaire (EQ5D) will be assessed every 3 cycles.

  9. Physical Function [ Time Frame: up to 5 years ]
    Physical function will be assessed using strength assessments (1RM), a cardiopulmonary exercise test (CPET) and a functional performance test (400m walk)

  10. Pain [ Time Frame: up to 5 years ]
    Pain will be assessed via questionnaire Brief Pain Inventory- short form (BPI-SF) and medical record review at entry with a lead-in period (<28 days) and repeated measures will occur every three cycles



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02730338


Contacts
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Contact: Anthony Treacy +61 (0)412872510 anthony.treacy@movember.com
Contact: Jennette Sison +01 415 885 3692 Jennette.Sison@ucsf.edu

  Show 25 Study Locations
Sponsors and Collaborators
Movember Foundation
University of California, San Francisco
Edith Cowan University
King's College London
Centre hospitalier de l'Université de Montréal (CHUM)
Epworth Foundation
Investigators
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Study Chair: Robert Newton Edith Cowan University
Study Chair: Fred Saad Centre hospitalier de l'Université de Montréal (CHUM)

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Movember Foundation
ClinicalTrials.gov Identifier: NCT02730338     History of Changes
Other Study ID Numbers: GAP4
First Posted: April 6, 2016    Key Record Dates
Last Update Posted: June 28, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Movember Foundation:
Castrate resistant
Exercise
Metastatic
Prostate cancer

Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases