Single-Dose Image-Guided Radiotherapy With Urethral Sparing and DIL Boost for Intermediate-Risk Prostate Cancer (PROSINT II)

NCT04035642 | Recruiting DMC

• 1 other identifier: PROSINT II
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective single-arm phase II study evaluates the safety, feasibility, quality-of-life effects, PSA kinetics, imaging response, and clinical outcomes of definitive ultra-high dose single-fraction external beam radiation therapy in patients with biopsy-proven NCCN intermediate-risk localized adenocarcinoma of the prostate. All eligible patients receive image-guided volumetric modulated arc radiotherapy with urethral sparing and organ-motion mitigation. Treatment consists of 24 Gy in one fraction to the whole prostate gland and proximal seminal vesicles. Patients with NCCN unfavorable intermediate-risk disease and an imaging-defined dominant intraprostatic lesion may receive a PSMA PET/CT-guided simultaneous integrated boost to the dominant intraprostatic lesion in sequential dose-escalation cohorts, up to 30 Gy, while maintaining protocol-defined organ-at-risk constraints. A rectal balloon with air filling is used for prostate target immobilization and anatomical reproducibility, and a urethral catheter loaded with beacon transponders is used to identify the urethra, support urethral sparing, and enable online target tracking. Toxicity is assessed using CTCAE v4.0, and patient-reported outcomes are assessed using EPIC-26, IPSS, and IIEF questionnaires. PSA is measured at protocol-defined follow-up visits. Multiparametric MRI is performed at baseline and at 12 and 24 months after treatment. Participants are followed for a minimum of 5 years.

Conditions

Prostate Cancer

Keywords

prostate cancer; PSMA PET/scan; dose escalation; simultaneous integrated boost

Outcome Measures

Primary Outcomes (1)

• Incidence of acute grade ≥2 GU and/or GI toxicity

  Proportion of treated participants with physician-assessed CTCAE v4.0 grade ≥2 genitourinary and/or gastrointestinal toxicity occurring from protocol treatment through 90 days after treatment.

  Treatment through 90 days after treatment

Secondary Outcomes (11)

• Late GU and GI toxicity

  >90 days

• Dose-limiting acute GU/GI toxicity

  Treatment through 90 days

• Quality-of-life change over time

  Baseline through 5 years

• Clinically meaningful EPIC-26 urinary decline

  Baseline through 90 days; longitudinally through 5 years

• Clinically meaningful urinary symptom worsening

  Baseline through 90 days; longitudinally through 5 years

Study Arms (1)

Single-dose IGRT-VMAT with urethral sparing ± PSMA-guided DIL-SIB

EXPERIMENTAL

Participants receive single-fraction image-guided volumetric modulated arc radiotherapy to the whole prostate gland and proximal seminal vesicles, with urethral sparing, rectal-balloon immobilization, and online tracking using a urethral catheter loaded with beacon transponders. The whole-gland prescription dose is 24 Gy in 1 fraction. Participants with NCCN unfavorable intermediate-risk disease and an imaging-defined dominant intraprostatic lesion may receive PSMA PET/CT-guided simultaneous integrated boost to the dominant intraprostatic lesion in sequential cohorts to 26.4 Gy, 28.8 Gy, or 30 Gy, while satisfying the same organ-at-risk constraints.

Radiation: IGRT-VMAT / SDRT 24 Gy in 1 fraction; Device: Rectal balloon with air filling; Device: Urethral catheter loaded with beacon transponders; Diagnostic Test: PSMA PET/CT for DIL definition and/or staging where protocol-required; Diagnostic Test: Planning MRI for organ at risk and target definition

Interventions

IGRT-VMAT / SDRT 24 Gy in 1 fraction RADIATION

PSMA PET/CT-guided dominant intraprostatic lesion simultaneous integrated boost

Single-dose IGRT-VMAT with urethral sparing ± PSMA-guided DIL-SIB

Urethral catheter loaded with beacon transponders DEVICE

A urethral catheter loaded with beacon transponders will be used to ensure set-up reproducibility and online target tracking.

Single-dose IGRT-VMAT with urethral sparing ± PSMA-guided DIL-SIB

Rectal balloon with air filling DEVICE

A rectal balloon with air filling will be used for prostate target immobilization and anatomical reproducibility.

Single-dose IGRT-VMAT with urethral sparing ± PSMA-guided DIL-SIB

Planning MRI for organ at risk and target definition DIAGNOSTIC_TEST

Planning MRI for organ at risk and target definition. mpMRI will also be used to aid DIL definition in conjunction with PSMA-PET/CT

Single-dose IGRT-VMAT with urethral sparing ± PSMA-guided DIL-SIB

PSMA PET/CT for DIL definition and/or staging where protocol-required DIAGNOSTIC_TEST

PSMA PET/CT for DIL definition

Single-dose IGRT-VMAT with urethral sparing ± PSMA-guided DIL-SIB

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet all of the following criteria:
• Signed study-specific informed consent form Histologic confirmation of adenocarcinoma of the prostate by biopsy Biopsy ISUP grade 1-3 Biopsy-proven localized intermediate-risk prostate cancer according to NCCN criteria No previous hormonal therapy PSA ≤20 ng/mL Staging multiparametric MRI confirmation of AJCC cT1c-cT2c disease, with no radiographic evidence of cT3, cT4, or N1 disease No direct evidence of regional or distant metastases after appropriate staging studies Age ≥18 years Performance status 0-2 IPSS score ≤15; alpha-blockers allowed CT- or ultrasound-based prostate gland volume estimate ≤100 grams

You may not qualify if:

• Participants with any of the following are ineligible:
• Positive lymph nodes or metastatic disease from prostate cancer on imaging studies MRI evidence of radiographic T3, T4, or N1 disease Biopsy ISUP grade ≥4 Previous pelvic radiotherapy Previous surgery for prostate cancer Previous transurethral resection of the prostate within 3 months Contraindication to protocol-required Foley catheter placement, rectal-balloon placement, MRI, PSMA PET/CT where required, or treatment immobilization/tracking procedures Active urinary tract infection, unresolved acute prostatitis, or other acute condition judged by the investigator to make simulation or SDRT unsafe until resolved Previous hormonal therapy History of Crohn's disease or ulcerative colitis Previous significant obstructive symptoms Significant psychiatric illness CT- or ultrasound-estimated prostate volume \>100 grams Severe active comorbidity judged by the investigator to preclude protocol treatment

Sponsors & Collaborators

• Fundacao Champalimaud: lead

Study Sites (1)

Champalimaud Foundation

Lisbon, 1400-038, Portugal

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Carlo Greco, MD

  Fundacao Champalimaud

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Carlo Greco, MD

CONTACT

+351210480048; carlo.greco@fundacaochampalimaud.pt

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 23, 2019
• First Posted: July 29, 2019
• Study Start: June 1, 2019
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2030
• Last Updated: May 8, 2026

Record last verified: 2026-05

Locations

PT (1)