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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02730338




Registration number
NCT02730338
Ethics application status
Date submitted
10/03/2016
Date registered
6/04/2016
Date last updated
28/06/2019

Titles & IDs
Public title
INTense Exercise foR surVivAL Among Men With Metastatic Castrate-Resistant Prostate Cancer
Scientific title
INTense Exercise foR surVivAL Among Men With Metastatic Castrate-Resistant Prostate Cancer
Secondary ID [1] 0 0
GAP4
Universal Trial Number (UTN)
Trial acronym
INTERVAL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer Metastatic 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Behaviour - High intensity aerobic and resistance training
Behaviour - Psychosocial support

Active Comparator: Arm A: Supervised exercise group - Supervised high intensity aerobic and resistance exercise tapering to self management with psychosocial support

Other: Arm B: Self directed exercise group - Self directed exercise and psychosocial support group


Behaviour: High intensity aerobic and resistance training


Behaviour: Psychosocial support


Intervention code [1] 0 0
Behaviour
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival - Overall survival will be measured from the time of randomization until death
Timepoint [1] 0 0
up to 5 years
Secondary outcome [1] 0 0
Disease Progression - 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).
Timepoint [1] 0 0
up to 5 years
Secondary outcome [2] 0 0
Symptomatic Skeletal Related Events (SSE) - 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
Timepoint [2] 0 0
up to 5 years
Secondary outcome [3] 0 0
Opiate Use - 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.
Timepoint [3] 0 0
up to 5 years
Secondary outcome [4] 0 0
Analgesic Use - 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.
Timepoint [4] 0 0
up to 5 years
Secondary outcome [5] 0 0
Biomarker analysis - Inflammatory and cytokine systemic milieu
Timepoint [5] 0 0
up to 5 years
Secondary outcome [6] 0 0
Biomarker analysis - Insulin/Glucose Metabolism
Timepoint [6] 0 0
up to 5 years
Secondary outcome [7] 0 0
Biomarker analysis - Androgen biosynthesis
Timepoint [7] 0 0
up to 5 years
Secondary outcome [8] 0 0
Quality of Life - 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.
Timepoint [8] 0 0
up to 5 years
Secondary outcome [9] 0 0
Physical Function - Physical function will be assessed using strength assessments (1RM), a cardiopulmonary exercise test (CPET) and a functional performance test (400m walk)
Timepoint [9] 0 0
up to 5 years
Secondary outcome [10] 0 0
Pain - 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
Timepoint [10] 0 0
up to 5 years

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
Yes
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC,WA
Recruitment hospital [1] 0 0
Australian Prostate Cncr Research Centre - Brisbane
Recruitment hospital [2] 0 0
GenesisCare Wesley - Brisbane
Recruitment hospital [3] 0 0
University of Queensland - Brisbane
Recruitment hospital [4] 0 0
Epworth Hospital - Melbourne
Recruitment hospital [5] 0 0
Victoria University / Sunshine Hospital - Melbourne
Recruitment hospital [6] 0 0
Edith Cowan University - Perth
Recruitment postcode(s) [1] 0 0
- Brisbane
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment postcode(s) [3] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Minnesota
Country [4] 0 0
United States of America
State/province [4] 0 0
Oregon
Country [5] 0 0
United States of America
State/province [5] 0 0
Washington
Country [6] 0 0
Canada
State/province [6] 0 0
Alberta
Country [7] 0 0
Canada
State/province [7] 0 0
Nova Scotia
Country [8] 0 0
Canada
State/province [8] 0 0
Ontario
Country [9] 0 0
Canada
State/province [9] 0 0
Montreal
Country [10] 0 0
China
State/province [10] 0 0
Chengdu
Country [11] 0 0
Germany
State/province [11] 0 0
Cologne
Country [12] 0 0
Ireland
State/province [12] 0 0
Dublin
Country [13] 0 0
Netherlands
State/province [13] 0 0
Rotterdam
Country [14] 0 0
United Kingdom
State/province [14] 0 0
Surrey
Country [15] 0 0
United Kingdom
State/province [15] 0 0
Bath
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Belfast
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Glasgow
Country [18] 0 0
United Kingdom
State/province [18] 0 0
London

Funding & Sponsors
Primary sponsor type
Other
Name
Movember Foundation
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
University of California, San Francisco
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Edith Cowan University
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
King's College London
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Centre hospitalier de l'Université de Montréal (CHUM)
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Epworth Foundation
Address [5] 0 0
Country [5] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02730338
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Robert Newton
Address 0 0
Edith Cowan University
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Anthony Treacy
Address 0 0
Country 0 0
Phone 0 0
+61 (0)412872510
Fax 0 0
Email 0 0
anthony.treacy@movember.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02730338