Clinical trial NCT05600400: Improving Sexual Quality of Life - Randomized Trial of Two vs Five MRI Guided SABR Treatments for Prostate Cancer
Official title: Improving Sexual Quality of Life - A Phase 2 Randomized Controlled Trial of Two Versus Five Stereotactic MRI-Guided Ablative Radiotherapy Treatments for Prostate Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Prostate Cancer
Cancer of Prostate
Prostate Adenocarcinoma
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
Collaborators: name: Prostate Cure Foundation
First posted: 2022-10-31
Enrollment: 144
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 2 fraction SBRT
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 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 outcomes:
measure: Toxicity in patients
timeFrame: Before treatment (Baseline); week 1, 4 and 13; month 6 and every 6 months for 5 years
measure: Proportion of patients with 4 year PSA value of <0.4 ng/ml
timeFrame: Before treatment (Baseline); months 3 and 6; and every 6 months for 5 years
measure: Biochemical Control in Prostate Patients
timeFrame: Before treatment (Baseline); months 3 and 6; and every 6 months for 5 years
measure: Salvage Therapy Rate
timeFrame: 5 years
measure: Health Utilities Outcome
timeFrame: 5 years
measure: Health Utilities Outcome
timeFrame: 5 years
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: Sunnybrook Health Sciences Centre
name: Danny Vesprini, MD
role: PRINCIPAL_INVESTIGATOR
References: