Improving Sexual Quality of Life - Randomized Trial of Two vs Five MRI Guided SABR Treatments for Prostate Cancer (iSMART)

Improving Sexual Quality of Life - A Phase 2 Randomized Controlled Trial of Two Versus Five Stereotactic MRI-Guided Ablative Radiotherapy Treatments for Prostate Cancer

Prostate Stereotactic ablative body radiotherapy (SABR) is an established technique that delivers radiation in a non-invasive approach for men with prostate cancer. The treatment regimen is given in total of 5 fractions with one treatment per day at every other day or weekly sessions. Ultra-hypofractionated radiotherapy (UHRT) is an emerging monotherapy for localized prostate cancer however, several trials have observed demonstrating superior biochemical control of a two-fraction (HDR) over single-fraction approach. The study aims to compare an experimental shorter course of prostate ultra-hypofractionated radiotherapy (UHRT) that will deliver what is expected to be an equivalent amount of radiation as given in the standard 5 treatment regimen. UHRT is given in 2 treatments with one treatment a week for 2 consecutive weeks.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer; Prostate Adenocarcinoma; Cancer of Prostate
• Intervention / Treatment: Radiation: Stereotactic Ablative Body Radiation

Detailed Description

Ultra-hypofractionated radiotherapy (UHRT) is an emerging monotherapy for localized prostate cancer. From a radiobiological standpoint, fewer fractions and higher doses per fraction takes greater advantage of the low α/β ratio of prostate cancer to improve the therapeutic ratio, most recently estimated at 1.6 based on 14 randomized controlled trials.Highly conformal delivery of large doses per fraction can be achieved with either high dose rate (HDR) brachytherapy or with stereotactic ablative radiotherapy (SABR).

Several trials have explored HDR as monotherapy, from 6-fractions to a single-fraction approach. Sunnybrook recently published a randomized trial of HDR monotherapy demonstrating superior biochemical control of a two-fraction over single-fraction approach. These and other data have informed the design of a phase III randomized controlled trial comparing two-fraction HDR monotherapy to low dose rate (LDR) brachytherapy in patients with intermediate risk prostate cancer (NCT02960087) coordinated by the Canadian Clinical Trails Group (PR19). The investigators have shown that 2 fraction SABR has equivalent efficacy and tolerability to 2 fraction HDR but SABR does not require general anesthesia, is less invasive and cheaper.

UHRT is also supported by phase III data, including a large non-inferiority randomized trial (HYPO-RT-PC) demonstrating similar biochemical control with a 7-fraction versus conventionally-fractionated regimen. The non-inferiority PACE-B trial comparing 5-fraction SABR to conventionally-fractionated or moderately hypofractionated RT has demonstrated similar acute toxicity with use of contemporary SABR planning techniques. Sunnybrook has also conducted several iterative clinical trials testing increasingly hypofractionated external beam radiotherapy. The investigators observed in parallel cohort studies that 5 fractions of UHRT and 2 fractions of UHRT with a patented immobilization device (GU-Lok) had equal effectiveness but better tolerability with the 2 fraction technique. As this was a post hoc analysis, this study aims to validate those findings.

• Study Type: Interventional
• Enrollment (Estimated): 144
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Danny Vesprini, MD; Phone Number: 4806 416-480-6100; Email: Danny.Vesprini@sunnybrook.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N3M5
      • Recruiting
      • Sunnybrook Health Sciences Centre
      • Contact: Daniel Vesprini, MD; Phone Number: 4164804806; Email: danny.vesprini@sunnybrook.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed prostate adenocarcinoma (centrally reviewed)

2. Low or favorable intermediate risk disease. Patient must meet one of the following categories:

   • Low risk - T1-T2b, grade group 1, AND PSA < 10 ng/ml;

   • Favorable risk

     1. Only one of the following intermediate risk factors - cT2c, grade group 2, or PSA 10-20 ng/ml; or
     2. Grade group 3 AND PSA < 20, AND <cT2c AND absolute percentage pattern 4/5 is <10%

Exclusion Criteria:

1. Androgen deprivation therapy (LHRH-agonists or antiandrogens) given or planned
2. Prior pelvic radiotherapy
3. Anticoagulation medication (if unsafe to discontinue for gold seed insertion)
4. Diagnosis of bleeding diathesis
5. Large prostate (>90cm3) on imaging
6. Immunosuppressive medications
7. Inflammatory bowel disease
8. Presence of dual hip prostheses
9. Contraindications to having MRI

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Two weekly fractions of 13.5 Gy	Radiation: Stereotactic Ablative Body Radiation; 2 Fraction; Other Names: SBRT
Active Comparator: Arm 2; Five every other day fractions of 8 Gy	Radiation: Stereotactic Ablative Body Radiation; 2 Fraction; Other Names: SBRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prostate Cancer Patient's Quality of Life Function will be measured to determine change in Quality of life function from baseline to 5 years beyond treatment.	Expanded Prostate Cancer Index Composite questionnaires will be scored and analyzed to determine change in Quality of life function from baseline	Change in patient Quaity of Life will be asseses from Before treatment (Baseline); week 1, 4 and 13; month 6 and every 6 months for 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity in patients	Incidence of acute Gastrointestinal (GI) and Genitourinary (GU) complications using CTCAE v4	Before treatment (Baseline); week 1, 4 and 13; month 6 and every 6 months for 5 years
Proportion of patients with 4 year PSA value of <0.4 ng/ml	Proportion of patients with 4 year PSA value of <0.4 ng/ml	Before treatment (Baseline); months 3 and 6; and every 6 months for 5 years
Biochemical Control in Prostate Patients	5 year biochemical failure rates using Phoenix definition (as nadir PSA +2ng/mL)	Before treatment (Baseline); months 3 and 6; and every 6 months for 5 years
Salvage Therapy Rate	Analysis of prostate patients requiring salvage treatment using Androgen Deprivation Therapy, surgery or brachytherapy	5 years
Health Utilities Outcome	Analysis of patient reported outcome using EQ-5D-5L	5 years
Health Utilities Outcome	Analysis of patient reported outcome using PORPUS-U	5 years

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Collaborators: Prostate Cure Foundation
• Investigators: Principal Investigator: Danny Vesprini, MD, Sunnybrook Health Sciences Centre

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: October 12, 2022
• First Submitted That Met QC Criteria: October 26, 2022
• First Posted (Actual): October 31, 2022

Study Record Updates

• Last Update Posted (Estimated): September 9, 2025
• Last Update Submitted That Met QC Criteria: September 2, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: iSMART

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
• product manufactured in and exported from the U.S.: No