Combined LDR Boost and HDR Whole Gland

Study Overview
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Brief Summary
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This is a dose finding Phase I/II study of combined focused LDR brachytherapy boost with whole gland single fraction HDR for men with low and intermediate risk prostate cancer and Dominant Intraprostatic Lesion (DIL) visible on multi parametric MRI. Patients will receive 19 Gy HDR to the whole gland with concurrent LDR brachytherapy boost to the DIL, in a sequential dose escalation manner. Primary endpoints are early toxicity.

Detailed Description
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Eligible patients will have low and intermediate risk prostate cancer with a dominant intraprostatic lesion definable on multi parametric MRI (PIRADS 4 or 5). Patients will have MR planned LDR focal brachytherapy to the DIL using iodine-125, while at the same time have single 19 Gy delivered to the whole prostate using ultrasound directed high dose-rate brachytherapy (HDR). The LDR boost dose will start at 50 Gy, and increase DIL dose in sequential cohorts of patients up until a dose of 80 Gy. Up to 20 patients will be included. Primary endpoint is toxicity at 3 months.

Official Title
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Dominant Intraprostatic Lesion Boost With Focused LDR Brachytherapy (BT) Integrated to Whole Prostate HDR BT: Safety and Feasibility Analysis

Conditions
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Carcinoma Prostate

Intervention / Treatment
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* Radiation: LDR/HDR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed Adenocarcinoma of the prostate Single PIRADS 4 or 5 lesion on multiparametric MRI T1c-T2b on rectal exam Gleason 3+3 and PSA < 20ng/mL Gleason 3+4 and PSA <10ng/mL Less than 50% of the cores positive in an untargeted prostate biopsy. Prostate volume < 60 cc Exclusion Criteria: Incapable or ineligible for MRI imaging Previous trans-urethral resection of prostate (TURP) Previous or current use of androgen deprivation Baseline International Prostate Symptom Score (IPSS) > 15 Evidence of distant or nodal metastasis Disease that contraindicates treatment with radiation (e.g connective tissue disease) Unsuitable for anesthesia due to comorbidity

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: Sequential dose escalation design
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LDR/HDR<br>MRI planned LDR boost to DIL with concurrent whole gland 19 Gy HDR. LDR dose will be sequentially escalated from 50 Gy to 80 Gy | Radiation: LDR/HDR<br>* Focal LDR to dominant lesion with whole gland 19 Gy HDR<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute urinary and rectal toxicity at 3 months as measured using NCI CTCAE v 4.0 | Acute urinary and rectal toxicity within the first 3 months as measured using NCI CTCAE v4.0 | At 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Late urinary and rectal toxicity using NCI CTCAE v4.0 | Cumulative incidence of urinary and rectal toxicity beyond 3 months using NCI CTCAE v4.0. | 3-monthly for first year, then 6-monthly until Year 5 | 
| Health related quality of life (HRQOL) changes | Changes in HRQOL as assessed using Expanded Prostate Index Composite (EPIC) | 3 monthly for first year, then annually year 1-5 | 
| Disease Free Survival | biochemical disease-free survival using PSA nadir + 2 ng/ml definition (Phoenix) | will be reported at 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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brachytherapy, LDR, HDR, monotherapy, focal