Hypofractionated Image-Guided Radiotherapy (IGRT) With Organ Motion Mitigation and Urethral Sparing for Prostate Cancer

NCT02761889 | Completed DMC

• 1 other identifier: HYPO
• Study Type: interventional
• Target: 444
• Locations: 1 country
• Sites: 1

Brief Summary

The present study evaluates the safety, feasibility, quality-of-life effects, PSA kinetics, and clinical outcomes of definitive dose-escalated external beam radiotherapy for localized adenocarcinoma of the prostate. Eligible patients will have biopsy-proven localized prostate adenocarcinoma without radiographic evidence of regional or distant metastases and without MRI evidence of radiographic T3/T4 disease. Patients may have low-risk, intermediate-risk, or selected high-risk disease. Previous or concomitant hormonal therapy is allowed but is not required, provided prior hormonal therapy was not given for more than 6 months before protocol therapy. Patients enrolled in the study will receive image-guided volumetric modulated arc radiotherapy (IGRT-VMAT) to 45 Gy in five fractions of 9 Gy each, delivered on five consecutive treatment days unless a clinically or operationally justified interruption is required. Treatment will use organ-motion mitigation, urethral localization, online target tracking, urethral sparing, and treatment-planning quality assurance procedures designed to support normal tissue sparing and accurate radiation delivery. A rectal balloon with air filling will be used for prostate immobilization and anatomical reproducibility, and a urethral catheter loaded with beacon transponders will be used for set-up reproducibility and online tracking. Patients will be followed at approximately 1 month after treatment, then at approximately 3, 6, 9, and 12 months, and every 6 months thereafter through 60 months. Patients will be followed for a minimum of 5 years. Follow-up assessments will include physician-graded gastrointestinal and genitourinary toxicity using NCI CTCAE v4.0, patient-reported urinary, bowel, and sexual quality-of-life outcomes using validated instruments including EPIC, IPSS, and IIEF questionnaires, and serum PSA testing. Biochemical relapse-free survival will be assessed using the Phoenix definition, and recurrence patterns will be summarized from clinically indicated imaging.

Conditions

Adenocarcinoma of the Prostate

Outcome Measures

Primary Outcomes (2)

• Acute treatment-related Grade ≥3 gastrointestinal or genitourinary toxicity

  Incidence of treatment-related Grade 3 or higher gastrointestinal or genitourinary adverse events, graded using NCI CTCAE version 4.0.

  From first protocol fraction through 90 days after completion of radiotherapy

• Late treatment-related Grade ≥2 gastrointestinal or genitourinary toxicity

  Incidence of treatment-related late Grade 2 or higher gastrointestinal or genitourinary adverse events, graded using NCI CTCAE version 4.0. Late Grade 3 or higher toxicity will be summarized separately.

  More than 90 days through 60 months after completion of radiotherapy

Secondary Outcomes (7)

• Change from baseline in urinary quality of life

  Baseline; approximately 1, 3, 6, 9, and 12 months; then every 6 months through 60 months

• Change from baseline in bowel quality of life

  Baseline; approximately 1, 3, 6, 9, and 12 months; then every 6 months through 60 months

• Change from baseline in sexual function

  Baseline; approximately 1, 3, 6, 9, and 12 months; then every 6 months through 60 months

• PSA kinetics after radiotherapy

  Approximately 1, 3, 6, 9, and 12 months; then every 6 months through 60 months

• Biochemical relapse-free survival

  Through 60 months or longer after completion of radiotherapy

Study Arms (1)

Experimental: Ultra-hypofractionated IGRT-VMAT 45 Gy in 5 fractions of 9 Gy

EXPERIMENTAL

Participants will receive definitive dose-escalated image-guided volumetric modulated arc radiotherapy for localized prostate adenocarcinoma. Radiotherapy will be delivered to 45 Gy in 5 fractions of 9 Gy each over 5 consecutive days, using organ-motion mitigation, urethral localization, online target tracking, urethral sparing, rectal balloon stabilization, and protocol-specified treatment planning and quality assurance procedures.

Radiation: Ultra-hypofractionated IGRT-VMAT with organ-motion mitigation and urethral sparing; Device: Rectal balloon with air filling; Device: Urethral catheter loaded with beacon transponders

Interventions

Rectal balloon with air filling DEVICE

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

Experimental: Ultra-hypofractionated IGRT-VMAT 45 Gy in 5 fractions of 9 Gy

Ultra-hypofractionated IGRT-VMAT with organ-motion mitigation and urethral sparing RADIATION

Image-guided volumetric modulated arc radiotherapy delivered to 45 Gy in 5 fractions of 9 Gy each. Treatment uses CT/MRI-based planning, a rectal balloon for target immobilization and anatomical reproducibility, a urethral catheter loaded with beacon transponders for localization and online tracking, and urethral dose sparing using inverse dose-painting when compatible with target coverage and disease anatomy.

Experimental: Ultra-hypofractionated IGRT-VMAT 45 Gy in 5 fractions of 9 Gy

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.

Experimental: Ultra-hypofractionated IGRT-VMAT 45 Gy in 5 fractions of 9 Gy

Eligibility Criteria

• Age: 40 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

Participants must meet all of the following criteria: * Signed study-specific informed consent. * Histologic confirmation of adenocarcinoma of the prostate by biopsy. * Localized low-risk, intermediate-risk, or selected high-risk adenocarcinoma of the prostate. Selected high-risk disease is limited to patients with no MRI evidence of radiographic T3/T4 disease and no radiographic regional or distant metastases. * No direct evidence of regional or distant metastases after appropriate staging studies. * Previous or concomitant hormonal therapy is allowed but not required. - Previous hormonal therapy must not have been given for more than 6 months before protocol therapy. * Age ≥40 years. * Performance status 0-2. * IPSS score ≤20; alpha blockers are allowed. * CT- or ultrasound-based prostate volume estimate ≤150 grams. Participants meeting any of the following criteria are ineligible: * Metastatic prostate cancer on imaging studies. * MRI evidence of radiographic T3 or T4 disease. * Previous pelvic radiotherapy. * Previous surgery for prostate cancer. * Previous hormonal therapy given for more than 6 months before protocol therapy. * History of Crohn's disease or ulcerative colitis. * Significant obstructive urinary symptoms, defined as IPSS \>20. * Significant psychiatric illness that would interfere with protocol participation. * Severe active comorbidity that, in the investigator's judgment, would preclude safe protocol therapy or required follow-up.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Fundacao Champalimaud: lead

Study Sites (1)

Champalimaud Foundation

Lisbon, 1400-038, Portugal

Location

Related Publications (1)

• Greco C, Pares O, Pimentel N, Louro V, Nunes B, Kociolek J, Marques J, Fuks Z. Early PSA density kinetics predicts biochemical and local failure following extreme hypofractionated radiotherapy in intermediate-risk prostate cancer. Radiother Oncol. 2022 Apr;169:35-42. doi: 10.1016/j.radonc.2022.02.016. Epub 2022 Feb 18.

  PMID: 35189157 DERIVED

Study Officials

• Carlo Greco, MD

  Fundacao Champalimaud

  PRINCIPAL INVESTIGATOR

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: Director Department of Radiation Oncology

Study Record Dates

• First Submitted: April 26, 2016
• First Posted: May 4, 2016
• Study Start: May 1, 2013
• Primary Completion: December 30, 2025
• Study Completion: December 30, 2025
• Last Updated: May 12, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

PT (1)