Clinical trial NCT06949254: PRospective Observational Study of STereotactic Body rAdiation Therapy With Androgen Deprivation Therapy for Organ-confined High-risk Prostate Cancer: the PROSTAR Trial
Official title: PRospective Observational Study of STereotactic Body rAdiation Therapy With Androgen Deprivation Therapy for Organ-confined High-risk Prostate Cancer: the PROSTAR Trial
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: High Risk Prostate Cancer
Lead sponsor: Istituto Clinico Humanitas
Sponsor class: OTHER
Collaborators: name: accord healthcare italia srl
First posted: 2025-04-29
Enrollment: 49
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients affected by localized high-risk prostate cancer candidate to radical radiotherapy

Brief summary: Prostate Cancer (PCa) is the second most common malignancy and the 5th common cause of cancer-related mortality in men worldwide. The majority of patients with PCa is diagnosed with potentially curable disease and its management includes different approaches, such as surgery, Radiation Therapy (RT) and Androgen Deprivation Therapy (ADT), for exclusive use or in combination each other. Randomized clinical trials have shown that moderate hypofractionated RT (i.e., 2.5-4 Gy per fraction) has become a valid alternative to conventionally fractionated RT in patients with PCa. The rationale of hypofractionation is based on the strong radiobiological evidence of the low α/β ratio of PCa cells (1.5-2 Gy) and the greater sensitivity to high dose per fraction. Data suggests that prostate Stereotactic Body Radiation Therapy (SBRT) is an alternative treatment strategy for localized PCa with promising results in terms of disease control and toxicity, not inferior to conventionally fractionated RT. A systematic review of over 6000 men underwent prostate SBRT on prospective studies has demonstrated that this treatment provides favorable patient's quality of life, excellent disease control, and results in minimal serious acute or late toxicity.

Almost all the published studies, investigated the role of SBRT for organ-confined low- and intermediate favorable-risk disease. However, the HYPO-RT-PC trial addressed the role of SBRT in the context of unfavorable localized PCa. In this non-inferiority, phase III multicenter trial 1200 patients with either intermediate or high risk PCa were enrolled. The aim of the study was to demonstrate that SBRT (42.7 Gy in 7 fractions, 3 days per week, for 2.5 weeks) is non-inferior to conventional fractionation (78 Gy in 39 fractions, 5 days per week for 8 weeks) regarding failure-free survival, without significant differences in late normal tissues complications. Failure-free survival at 5 years was 84% in both treatment arms; adjusted HR was 1.002, hence ultra-hypofractionation was found to be non-inferior to conventional fractionated RT (given HR limit = 1.338). These results paved the way for the use of SBRT even in patients with unfavorable PCa. One controversial issue is the role of ADT in the setting of SBRT for localized PCa: in conventionally fractionated schedules, short term (4-6 months) and long term (1.5-3 years) ADT are considered the standard of care for unfavorable intermediate and high-risk PCa, respectively. However, in a systematic review/meta-analysis no benefit was found for ADT added to SBRT and similar results were reported also by King et al. in a retrospective study on over 1000 patients. The PACE C trial is one of three cohort of PACE that is multicenter, international phase 3 randomized controlled study. PACE C is set to explore the efficacy of SBRT in combination with ADT for patients with unfavorable intermediate and high-risk PCa and will recruit 1182 patients who will be randomized to receive either hypofractionated RT (60 Gy in 20 fractions) or SBRT delivered with 36.25 Gy in 5 fractions.

In this scenario, our study aims to evaluate the safety and efficacy of SBRT (40 Gy in 5 fractions every other day) coupled with ADT (relugolix 18-24 monthsaccording to clinical care) in patients with localized high-risk PCa.


Eligibility criteria: Inclusion Criteria:

* Age \> 18 years
* ECOG performance status ≤ 2
* Histologically proven prostate adenocarcinoma
* High-risk group classification according to National Comprehensive Cancer Network (NCCN), defined by the presence of any one of the following high-risk factors: cT3-cT4 OR Grade Group 4 or Grade Group 5 OR PSA \>20 ng/mL
* No pelvic nodal and distant metastases at staging with PSMA-PET
* IPSS ≤ 15 (alpha blockers allowed)
* Life expectancy of \> 5 years
* Prostate volume ≤ 100 cc

Exclusion Criteria:

* Previous local radiation treatment of the prostate
* Previous radiotherapy to the pelvis
* Active Ulcerative Colitis or Crohn's Disease
* Previous tumors unless disease free for a minimum of 5 years

Primary outcomes:
measure: Assessment of treatment efficacy: Biochemical-relapse free survival at 2 years (defined as rising PSA > 2 ng/mL above post-SBRT nadir).
timeFrame: from baseline to two years
Secondary outcomes:
measure: Biochemical-relapse free survival at 5 years (defined as rising PSA > 2 ng/mL above post-SBRT nadir)
timeFrame: from baseline to 5 years
measure: Distant-metastases free survival at 2 years and 5 years
timeFrame: from baseline to 5 years
measure: Cancer-specific survival at 2 and 5 years
timeFrame: from baseline to 5 years
measure: Analysis of ctDNA in a series of prospectively collected PCa patients
timeFrame: from baseline to 5 years
measure: The role of ctDNA clearance as a biomarker to intercept the molecular relapse
timeFrame: from baseline to 5 years
measure: EORTC QLQ-C30 for quality of life
timeFrame: from baseline to 5 years
measure: - EORTC PR-25 questionnaires for the GU, GI and sexual domains at baseline and follow-up visits
timeFrame: from baseline to 5 years
measure: International Prostatic Symptoms Score (IPSS)
timeFrame: from baseline to 5 years
measure: Urinary Incontinence (ICIQ-SF)
timeFrame: from baseline to 5 years
measure: International Index of Erectile Function 15 Item
timeFrame: from baseline to 5 years
measure: Serum PSA and testosterone levels at follow-up visits
timeFrame: from baseline to 5 years
Other outcomes:
Locations:
city: Rozzano
country: Italy
facility: IRCCS Humanitas Research Hospital
state: Milan
city: Bergamo
country: Italy
facility: Humanitas Gavazzeni
city: Milan
country: Italy
facility: Humanitas PIO X
Study officials:
References: