INTense ExeRcise for surviVAL Among Men With Metastatic Prostate Cancer (INTERVAL - GAP4)

• Register: ClinicalTrials.gov
• Last refreshed on: 27 March 2023
• Main ID: NCT02730338
• Date of registration: 10/03/2016
• Prospective Registration: No
• Primary sponsor: Movember Foundation
• Public title: INTense ExeRcise for surviVAL Among Men With Metastatic Prostate Cancer (INTERVAL - GAP4) INTERVAL
• Scientific title: INTense ExeRcise for surviVAL Among Men With Metastatic Prostate Cancer (INTERVAL - GAP4): A Multicentre, Randomised, Controlled, Phase III Study
• Date of first enrolment: January 2016
• Target sample size: 866
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT02730338
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: N/A

Countries of recruitment

Australia, Canada, China, Germany, Ireland, Netherlands, United Kingdom, United States

Contacts

• Name: Fred Saad
• Affiliation: Centre hospitalier de l'Université de Montréal (CHUM)

• Name: Robert Newton
• Affiliation: Edith Cowan University

Key inclusion & exclusion criteria

Inclusion Criteria:

mCRPC status:

- mCRPC patients defined as; adenocarcinoma of the prostate with systemic metastatic
disease despite castrate levels of testosterone (<50 ng/dL) due to orchiectomy or LHRH
agonist.

o 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).

- PSMA PET/CT scan progression: Appearance of one or more new lesions on PSMA PET/CT
scan attributable to prostate cancer.

- At enrolment, mCRPC 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 / or Docetaxel, Cabazitaxel or other
approved first line chemotherapy; 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, Cabazitaxel or other approved first line
chemotherapy as first line for mCRPC who are asymptomatic without ANY evidence of
progression Or

5. Patients may have progressed following first line Docetaxel, Cabazitaxel or other
first line chemotherapy 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 estimated life
expectancy of more than 1 year.

mHSPC Status:

- mHSPC patients must be classified as either high-risk or high-volume mHSPC. These
groups are defined as adenocarcinoma of the prostate with systemic metastatic disease
and patients also fit into one of the following 2 categories: 6. High-risk: defined as
having at least 2 of three criteria: (i) Gleason score =8, (ii) presence of =3 lesions
on bone scan, or (iii) presence of INTERVAL Protocol Version 5.0, 19 August 2019 4
measurable visceral lesions (PSMA PET imaging should not be used in the definition of
high-risk disease) Or 7. High-volume: defined as having the presence of visceral
metastases and/or = four bone metastases with at least one outside of the vertebral
column and pelvis (PSMA PET imaging should not be used in the definition of
high-volume disease)

Additional criteria for all groups:

- 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.

- =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 =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 as designated by the institution at which he
would be enrolled.



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

Health Condition(s) or Problem(s) studied

Metastatic Prostate Cancer

Intervention(s)

Behavioral: Psychosocial support

Behavioral: High intensity aerobic and resistance training

Primary Outcome(s)

Overall Survival [Time Frame: up to 5 years]

Secondary Outcome(s)

Analgesic Use [Time Frame: up to 5 years]

Quality of Life [Time Frame: up to 5 years]

Disease Progression [Time Frame: up to 5 years]

Pain [Time Frame: up to 5 years]

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

Opiate Use [Time Frame: up to 5 years]

Physical Function [Time Frame: up to 5 years]

Biomarker analysis [Time Frame: up to 5 years]

Secondary ID(s)

GAP4

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Edith Cowan University

University of California, San Francisco

King's College London

Centre hospitalier de l'Université de Montréal (CHUM)