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INTERVAL - Intense Exercise Trial for 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: NCT04507698
Recruitment Status : Recruiting
First Posted : August 11, 2020
Last Update Posted : August 11, 2020
Sponsor:
Collaborators:
Movember Foundation
Queen's University, Belfast
University of Glasgow
University of Bristol
University of Surrey
Information provided by (Responsible Party):
Guy's and St Thomas' NHS Foundation Trust

Brief Summary:

Exercise has been established to be safe and result in improved physical function and quality of life for most individuals with cancer. However, little information exists regarding whether exercise can increase overall survival and reduce disease progression, events related to cancer spreading to the bones (e.g. bone fracture, spinal cord compression, extra radiation or surgery), and pain in patients with metastatic prostate cancer that is no longer responding to hormone therapy. The primary objective of this study is to determine if high intensity aerobic and resistance training plus psychosocial support increases overall survival compared to psychosocial support alone in prostate cancer patients.

The Movember foundation is providing support for the conduct of this study


Condition or disease Intervention/treatment Phase
Prostate Cancer Other: Intensive Exercise Intervention Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: INTense Exercise foR surVivAL Among Men With Metastatic Castrate-Resistant Prostate Cancer (INTERVAL - MCRPC): A Multicentre, Randomised, Controlled, Phase III Study
Actual Study Start Date : September 1, 2017
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Supervised Exercise Arm
If participants are placed in the Supervised Exercise Group, they will attend supervised group exercise sessions, which are individually tailored to the participants physical condition, at least once a week, every week for the first year of the study. They will be asked to exercise 3 times a week.
Other: Intensive Exercise Intervention
INTense Exercise foR surVivAL among Men with Metastatic Castrate-Resistant Prostate Cancer (INTERVAL - MCRPC), randomised to either the supervised exercise arm or the self-directed exercise arm.

No Intervention: Self-Directed Exercise Arm
If Participants are placed in the Self-directed Exercise Group, they will receive usual medical care (standard of care) and be asked to follow their usual exercise and lifestyle routine. They will receive supportive care in the form of newsletters, covering a variety of topics including pain management, bone health, goal setting, taking control of life, and more.



Primary Outcome Measures :
  1. Overall Survival [ Time Frame: 24 months ]
    Patients will be followed for death a minimum of 36 months after randomisation. Overall survival will be measured from the time of randomisation until death. Medical records and death certificates will be reviewed every 6 months to obtain survival status. Country-specific mortality status databases will also be searched annually; cause of death will be determined through review of medical and death records. Patients will be contacted once a year, and follow up with next of kin then alternate contact, if needed, if we do not hear from them.


Secondary Outcome Measures :
  1. Disease progression [ Time Frame: 24 months ]

    Progression will be determined by the treating physician, and may include any of the following, based on PCWG-3 and RECIST 1.1 criteria:

    • Bone scan: Appearance of ≥ 2 new lesions on bone scan, if bone scan >12 weeks after randomisation
    • CT/MRI: ≥ 20% increase in the sum of diameters, taking the reference as the smallest sum on study. In addition to the relative increase by 20%, the sum must also demonstrate an absolute increase >5 mm / appearance of one or more new lesions / Unequivocal progression of baseline unmeasurable lesions.
    • initiating a new therapy for MCRPC
    • Symptomatic-skeletal related event (SSE). Progression free survival will be measured from randomisation 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 SSE.

    CT Scan Progression of Non-measurable Lesions Progression will be defined based on PCWG;-3 and RECIST 1.1 as all other lesions, including


  2. Symptomatic Skeletal Related Events [ Time Frame: 24 months ]

    Time to first occurrence of SSE will be defined as the time from randomisation 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

    Adverse event, concomitant medication, concomitant treatment, or survival follow-up CRFs and the participant's medical record will be the source of these findings and presented as categorical data.


  3. Analgesic/Opiate Use [ Time Frame: 24 months ]

    Analgesic/opiate use will be assessed via Brief Pain Inventory - Short Form (BPI-SF) questionnaire and 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 BPI-SF questionnaires will be administered every three cycles until month 24, and yearly thereafter.

    BPI-SF scoring:Score: 1 - 4 = Mild Pain, Score: 5 - 6 = Moderate Pain, Score: 7 - 10 = Severe Pain.

    WHO scoring: 1 = non-opiods (e. g. acetaminophen), 2 = as necessary, mild opiods (e. g. codeine), 3 = then strong opiods (e. g. morphine or hydromorphone) until the patient is free of pain.


  4. Metabolic Biomarkers [ Time Frame: 24 months ]
    Inflammatory and cytokine systemic milieu: Serum/plasma aliquots (baseline and cycle 6) from all patient samples are intended for interrogation of a panel of markers associated with inflammation including IL1β, IL-2, IL-6, TNFα and adiponectin. Results from these investigations will be correlated with c-reactive protein and measured outcomes of exercise response and disease progression. Insulin/Glucose Metabolism: Serum aliquots (baseline and cycle 6) from all patient samples are intended for assessment of insulin levels by e.g. enzyme-linked immunosorbent assay (ELISA). Insulin sensitivity will be calculated using these fasting serum insulin values and plasma glucose determinations obtained in the additional clinical blood assessments, where the HOMA-IR method will be applied. C-peptide will also be assessed. Androgen biosynthesis: Serum aliquots from all patient samples at baseline are intended for assessment of androgen levels (Testosterone, DHT, androstenedione, DHEA, 17-hydroxy.

  5. Physical Function [ Time Frame: 24 months ]
    Physical function will be assessed using strength assessments (1RM), a cardiopulmonary exercise test (CPET) and a functional performance test (400m walk). Strength assessments will be quantified in kilograms lifted, and will be dependent upon the location and size of bone metastatic lesions present as to which tests are performed (Chest Press, Leg Press, Seated Row and Leg Extension). All strength assessments should be attempted if not contraindicated. Cardiopulmonary exercise capacity will be quantified by VO2peak (L.min and mL/(kg·min)) and workload achieved (watts) during a successful CPET (RPE ≥

  6. Quality of Life - Patient Reported Outcome Measures [ Time Frame: 24 months ]
    Symptoms will be considered independently of other outcome measures. Pain will be assessed via BPI-SF and medical record review at entry with a lead-in period (<28 days) and repeated measures will occur every three cycles. Changes occurring within 12 weeks of study initiation will be ignored in the absence of compelling evidence of disease progression. Response or progression of pain will be confirmed through repeat assessments separately by at least three weeks. Quality of life measured by the FACT-G, FACIT-Fatigue, QLQ-C30, EPIC-26, and EQ5D will be assessed every 3 cycles.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Male prostate cancer patients
Accepts Healthy Volunteers:   No
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 i.e.: 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 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 INTERVAL Protocol Version 4.0, 19 April 2018 4

    ≥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

Exclusion Criteria:

  • Previous radiographic or clinical progression (PSA progression is permitted) while on treatment with abiraterone, enzalutamide, apalutamide, 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)
  • 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.

If patient is currently taking hypertensive medication(s)/therapy, please indicate medication and include in the Treatment and Concomitant Medications Log (SOM: Appendix 11).

  • 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.
  • 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 in the mCRPC state. 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 structured INTERVAL Protocol Version 4.0, 19 April 2018 15 Resistance exercise two or more days per week (seek ECC approval before exclusion).

Experiences shortness of breath, chest discomfort, or palpitations when performing activities of daily living (patient with these symptoms can participate in the study with cardiologist clearance)

  • Ongoing restriction of physical activity with physician documentation
  • Has chest pain brought on by physical activity (patient can participate in the study with cardiologist clearance)
  • Has developed chest pain in the past month (patient can participate in the study with cardiologist clearance)
  • 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 country-specific FFQ 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): NCT04507698


Contacts
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Contact: Harriet Wylie 07464492509 harriet.wylie@gstt.nhs.uk

Locations
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United Kingdom
Queens University Belfast Recruiting
Belfast, Northern Ireland, United Kingdom
Contact: Joe O'Sullivan       joe.osullivan@qub.ac.uk   
Contact: Mal Brown       m.brown@qub.ac.uk   
University of Glasgow Recruiting
Glasgow, United Kingdom
Contact: Hing Leung       h.leung@beatson.gla.ac.uk   
Contact: Christian Delles       christian.delles@glasgow.ac.uk   
Guy's and St Thomas's NHS Trust Recruiting
London, United Kingdom, SE1 9RT
Contact: Harriet Wylie    07464492509    harriet.wylie@gstt.nhs.uk   
Contact: Anna Haire    07464492509    anna.haire@gstt.nhs.uk   
University of Surrey Recruiting
London, United Kingdom
Contact: Harry Roberts       interval@surrey.ac.uk   
Contact: Ralph Manders       r.manders@surrey.ac.uk   
Sponsors and Collaborators
Guy's and St Thomas' NHS Foundation Trust
Movember Foundation
Queen's University, Belfast
University of Glasgow
University of Bristol
University of Surrey
  Study Documents (Full-Text)

Documents provided by Guy's and St Thomas' NHS Foundation Trust:
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Responsible Party: Guy's and St Thomas' NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT04507698    
Other Study ID Numbers: 201101
First Posted: August 11, 2020    Key Record Dates
Last Update Posted: August 11, 2020
Last Verified: August 2020

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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 Guy's and St Thomas' NHS Foundation Trust:
Metastatic
Castrate
Prostate
Cancer
Resistant
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases