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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Oligometastatic Prostate Cancer
• Intervention / Treatment: Radiation: Hypofractionated external beam radiotherapy; Radiation: High dose rate brachytherapy; Radiation: Permanent seed implant; Radiation: Stereotactic body radiotherapy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 168
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Juanita Crook, MD; Phone Number: 250 712 3958; Email: jcrook@bccancer.bc.ca

Study Locations

• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y5L3
      • Recruiting
      • British Columbia Cancer Agency Center for the Southern Interior
      • Principal Investigator: Juanita Crook, MD
      • Sub-Investigator: David Kim, MD
      • Contact: Juanita Crook, MD; Phone Number: 250 712 3958; Email: jcrook@bccancer.bc.ca
      • Sub-Investigator: Deidre Batchelar, PhD
      • Sub-Investigator: Cynthia Araujo, PhD
      • Sub-Investigator: David Petrik, MD
      • Sub-Investigator: Michelle Hilts, PhD
      • Sub-Investigator: Ross Halperin, MD
      • Sub-Investigator: Halperin Ross, MD
    • Surrey, British Columbia, Canada
      • Not yet recruiting
      • Fraser Valley Cancer Center
      • Contact: Winkle Kwan, MD; Email: wkwan@bccancer.bc.ca
    • Vancouver, British Columbia, Canada
      • Not yet recruiting
      • Vancouver Cancer Center
      • Contact: Mira Keyes, MD; Phone Number: 604-266-6444; Email: mkeyes@bccancer.bc.ca
    • Victoria, British Columbia, Canada
      • Recruiting
      • Vancouver Island Cancer Center
      • Contact: Saibishkumar Elantholi Parmeswaran, MD; Email: skumar@bccancer.bc.ca
      • Sub-Investigator: Jordan Wong, MD
      • Sub-Investigator: Jonathan Livergant, MD
      • Sub-Investigator: Howard Pai, MD
      • Sub-Investigator: Abe Alexander, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: standard; External beam radiotherapy to deliver 5500 centiGray (cGy) in 20 fractions to the prostate over 4 weeks	Radiation: Hypofractionated external beam radiotherapy; 5500 cGy/20 fractions delivered 5 days per week over 4 weeks
Experimental: High dose rate brachytherapy; A single fraction of 19 Gray (Gy) is delivered to the prostate under anesthesia as an out patient.	Radiation: High dose rate brachytherapy; A single fraction of 19 Gy is delivered from an automated afterloading Iridium-192 source via interstitial catheters placed under ultrasound guidance
Experimental: Permanent seed implant brachytherapy; 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; Iodine-125 radioactive seeds are implanted permanently in the prostate in a single procedure under transrectal ultrasound guidance; Other Names: Low dose rate brachytherapy
Experimental: Stereotactic body radiotherapy; 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; 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.; Other Names: SABR

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: British Columbia Cancer Agency
• Investigators: Principal Investigator: Juanita Crook, MD, BCCancer

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2021
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: October 14, 2020
• First Submitted That Met QC Criteria: October 26, 2020
• First Posted (Actual): October 30, 2020

Study Record Updates

• Last Update Posted (Actual): December 18, 2023
• Last Update Submitted That Met QC Criteria: December 14, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: radiotherapy; brachytherapy; hypofractionation; prostate adenocarcinoma; oligometastases
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: H20-01207

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No