5500/20 vs. SABR or Brachytherapy for PRimary OligoMetastatic Prostate Cancer Treatment (PROMPT)

Study Overview
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Brief Summary
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We will investigate whether ultrahypofractionation using stereotactic ablative radiotherapy (SABR) or brachytherapy is as well-tolerated as moderately hypofractionated external beam radiotherapy (EBRT) for treating the prostate in patients with oligometastatic prostate cancer. Secondary aims include assessment of progression-free survival (PFS) and overall survival (OS) as well as cost-effectiveness. We hypothesize that ultrahypofractionation will maintain favorable toxicity profiles and quality of life while achieving comparable or better efficacy, thereby providing a convenient and cost-effective alternative to moderately hypofractionated EBRT.

Detailed Description
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Men newly diagnosed with low volume oligometastatic prostate cancer defined as fewer than 5 bone metastases and/or non regional lymph node involvement who agree to treatment of the primary cancer with radiation will be randomized between standard moderately hypofractionated external radiotherapy (5500 centiGray/20 fractions as per Stampede trial) and one of 3 alternatives: stereotactic body radiotherapy (SABR) to deliver 36 Gy/5 fractions, or low dose rate Iodine 125 permanent seed implant or a single high dose rate temporary implant. The trial will take place in 4 regional cancer centers of British Columbia Cancer Agency, with each center choosing their preferred alternative to 5500/20. To achieve 4 equally sized treatment arms, each randomization is weighted 3:1 for 42 patients in each arm and 168 total accrual. The primary endpoint is urinary quality of life as assessed by the International Prostate Symptom Score (IPSS) . As the typical acute symptoms from each of these radiation modalities has a unique time course, assessments are done at 6 different points during the first 2 years. Secondary endpoints are global quality of life as assessed by Expanded Prostate Cancer Index (EPIC) urinary, bowel and sexual scores, progression free survival, overall survival and cost effectiveness.

Official Title
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Moderate Versus Ultra Hypofractionation or Brachytherapy for PRimary OligoMetastatic Prostate Cancer Treatment

Conditions
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Oligometastatic Prostate Cancer

Intervention / Treatment
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* Radiation: Hypofractionated external beam radiotherapy
* Radiation: High dose rate brachytherapy
* Radiation: Permanent seed implant
* Radiation: Stereotactic body radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to provide informed consent European Cooperative Oncology Group performance status 0 to 2 Medically fit for all protocol treatment and follow-up Histologically confirmed adenocarcinoma of the prostate Newly diagnosed any Tumor stage, any Nodal stage but with oligo metastases No prior therapy for prostate cancer apart from androgen deprivation Luteinizing Hormone Releasing Hormone (LHRH) agonists or antagonists must have started within 24 weeks of randomization If used, anti-androgens must have started within 26 weeks of randomization Able to complete the necessary investigations prior to and within 12 weeks of starting Androgen Deprivation Therapy (ADT) or of randomization (History and physical examination, PSA) Able to complete the necessary investigations priOr to start of Radiotherapy (Transrectal ultrasound-guided biopsy, CT chest, abdomen & pelvis or MRI abdomen and pelvis, and Bone scan) Planned for long-term androgen deprivation therapy Exclusion Criteria: High metastatic burden defined as 5 or more bone metastases or visceral metastases Abnormal liver function Contraindications to EBRT such as active inflammatory bowel disease or previous pelvic radiation Medically unfit for anesthesia International Prostate Symptom Score (IPSS) greater than 20 Restrictive flow pattern with peak flow rate less than10 mL per second or post-void residual greater than 25 per cent of voided volume (when uroflowmetry available) Prostate volume greater than 60cc after maximal cytoreduction Pubic arch interference Transurethral resection of prostate (TURP) within 12 weeks of brachytherapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: There is one standard arm (5500/20) and 3 alternative arms. The alternative arms are center (or investigator) specific. Thus, each randomization is 2-way, but with a 3:1 weighting so that the 4 treatment arms have equal numbers of patients.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: standard<br>External beam radiotherapy to deliver 5500 centiGray (cGy) in 20 fractions to the prostate over 4 weeks | Radiation: Hypofractionated external beam radiotherapy<br>* 5500 cGy/20 fractions delivered 5 days per week over 4 weeks<br>|
| Experimental: High dose rate brachytherapy<br>A single fraction of 19 Gray (Gy) is delivered to the prostate under anesthesia as an out patient. | Radiation: High dose rate brachytherapy<br>* A single fraction of 19 Gy is delivered from an automated afterloading Iridium-192 source via interstitial catheters placed under ultrasound guidance<br>|
| Experimental: Permanent seed implant brachytherapy<br>A single permanent implant of radioactive Iodine-125 seeds is performed under anesthesia as an out patient to deliver 125 Gy to the prostate | Radiation: Permanent seed implant<br>* Iodine-125 radioactive seeds are implanted permanently in the prostate in a single procedure under transrectal ultrasound guidance<br>* Other names: Low dose rate brachytherapy;|
| Experimental: Stereotactic body radiotherapy<br>36.25 Gy is delivered to the prostate in 5 fractions given either weekly or every second day, using a SABR technique. | Radiation: Stereotactic body radiotherapy<br>* External radiation using SABR technology delivers 36.25 Gy to the prostate in 5 fractions given either once weekly for 5 weeks or every second day over 2 weeks.<br>* Other names: SABR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary symptoms | International Prostate Symptom score (0/35), higher worse | Baseline to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expanded Prostate Cancer Index (EPIC) urinary domain | Urinary Quality of life, 0/100 higher score better | Baseline to 2 years | 
| EPIC bowel domain | Bowel quality of life, 0/100, higher score better. Series of validated questions concerning urgency, frequency, consistency, leakage, presence of blood and pain with bowel movements and then rates how big a problem each symptom was (0-5) | Baseline to 2 years | 
| EPIC sexual domain | Sexual quality of life, 0/100, higher score better. Series of validated questions concerning frequency and quality of erections, presence of morning erections, ability to engage in sexual activity or intercourse, rates ability and then rates importance of each issue to the patient. | Baseline to 2 years | 
| Biochemical failure (time to increase in prostate specific antigen (ng/ml) to 50% > nadir | Progression free survival measured as time to Prostate Specific Antigen (PSA) rise by 50% > nadir | Baseline to 3 years | 
| Distant metastatic failure | Progression free survival measured as time to new or progressive bone metastases | Baseline to 3 years | 
| Nodal progression | Progression free survival measured as new or progressive adenopathy on imaging | Baseline to 3 years | 
| Overall survival | Overall survival regardless of cause of death | 3 years | 
| Cause specific survival | Death from prostate cancer | Within 3 years of treatment | 
| Cost effectiveness | Analysis of primary treatment costs and secondary treatment costs at time of progression | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prostate adenocarcinoma, oligometastases, radiotherapy, hypofractionation, brachytherapy