Clinical trial NCT05786742: Ultra Hypofractionnated Radiotherapy With HDR Brachytherapy Boost.
Official title: ULTRA-HYPO Fractionated (UHF) Compared to Moderate-HYPO Fractionated (MHF) Prostate IGRT With HDR Brachytherapy BOOST : A Phase 1-2 Study.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Prostate Cancer
Radiotherapy Side Effect
Hypofractionation
Brachytherapy
Radiotherapy
Localized Prostate Carcinoma
Keywords: hypo fractionation
brachytherapy
Ultra Hypo fractionation
Lead sponsor: CHU de Quebec-Universite Laval
Sponsor class: OTHER
First posted: 2023-03-28
Enrollment: 205
Sex: MALE
Minimum age (years): 18
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective comparative cohort study with non inferiority analysis UH-IMRT combined to 15 Gy HDR Brachytherapy will considerably reduce the treatment fraction delivered while maintaining b-DFS and Side-effects at comparable levels to our actual reported prostate cancer patient population, without lymph nodes involvement (risk being less than 15%). We believe that this therapeutic regime will show to be non-inferior to our actual standard therapeutic regime
Primary purpose: TREATMENT

Brief summary: Phase 1-2 study, comparing ultra-hypofractionnated (UH) to a moderately hypofractionnated (MH) radiation therapy, with image guided HDR prostate brachytherapy. Using iso-equivalent doses, a non-inferiority analysis will be done in order to prove UH non-inferior to MH, toxicity wise. Acceptability, tolerability, acute and late toxicity will be reported. MRI visible dominant intra-prostatic lesion will be outlines and variability between radiation oncologists and radiologists will be reported. As secondary objective, biochemical and clinical failure free survival will be reported at 5 \& 10 years.

Detailed description: Phase 1 : consists in a feasibility study (First 28 patients).

Phase 2 : monocentric prospective comparative cohort study.

Recruitment :

* "Centre intégré de cancérologie du CHU de Québec-Université Laval."
* Recruitment period: December 2015 to June 2023

Brachytherapy :

* Implantation under general or spinal anesthesia
* Foley catheter insertion in bladder.
* TRUS prostate localisation.
* Prostate volume measurement.
* Gold fiducial markers (3) insertion.
* Prostate brachytherapy catheters (14 à 21) insertion.
* Cystoscopy for bladder and urethra integrity control.
* Re-insertion of foley catheter after cystoscopy.

Planning imaging: TRUS or CT scan (has needed).

Structures delineation by radiation oncologist (brachytherapist).

* Prostate
* Seminale vesicles
* Rectum
* Colon sigmoïde
* Bladder
* Urethra
* Penile bulb

Dosimetric optimisation

* Oncentra Prostate v. 4.2.2 d'Elekta brachytherapy (Veenendaal, The Netherlands)
* Oncentra Brachy version 4.6 (if under CT scan).

Treatment (brachytherapy dose delivery).

* 15 Gy in one fraction
* Direct interstitial dose monitoring (20 patients or more). Fiber-optic dosimeter inserted in prostate brachytherpy catheter for live dose delivery mesurements.

Foley ablation under full bladder, same day or day after therapy.

Radiotherapy:

* Via IMRT, VMAT or SBRT technics.
* Dose : 25 Gy in 5 fractions administered over a 7 days period. 2 to 3 fractions separated by 2 days, weekend break.
* PTV includes prostate and the first centimeter of seminal vesicle.

Simulation

* one week post brachytherapy
* standard has described in the department procedure manual.
* maximal CT scan slice thickness : 2-3mm.
* uretro-graphy done to identify urogenital sphincter.

Multiparametric MRI

* If no counter-indication and available,
* a T2 tridimensional sequence for prostate delineation
* slice thickness : 1 mm.
* a diffusion weighted sequence will be done.
* a DTI with tractography can be done optionally.
* contrast media (gadolinium) is optional.

Physique

* Linac energy (between 6 MV to 18 MV).
* ARC therapy technique will be used
* planification softwares: Éclipse, Pinnacle or Raystation.
* Portal (kV-kV) imagery will be used for marker match.
* CBCT will be done at each fraction delivered.

Clinical and dosimetric data will be collected prior treatment.

Primary objectives :

* Toxicity analysis will be quantitatively evaluated using CTCAE (v5) at 1, 2 and 5 years post-therapy, and has needed at FU visits. Kaplan-Meier statistical analysis will be used to report toxicity evolution through time.
* median IPSS scores will be reported at 3, 6, 12 months and yearly (1, 2, 3, 4 et 5) post-therapy. IPSS median time to baseline return will be calculated.
* IPSS urinary scores, sexual function (SHIM) and GI toxicity (CTCAE-v5) and quality of life questionnaires ( EPIC-26) will be given at 3, 6 months and yearly thereafter (1, 2, 3, 4 et 5) post-treatment.

Secondary objectives : Biochemical disease-free survival has per Phoenix definition (by American Society of Radiation Oncology - ASTRO) recommendation will be reported using Kaplan-Meier analysis.

Eligibility criteria: Inclusion Criteria:

* Biopsy proven Prostate adenocarcinoma
* Stage T1c, T2 (Annex 2)
* Stage Nx or N0
* Stage Mx or M0
* PSA \< 20ng/ml
* Gleason Score 6 or 7
* Having the ability to sing a written consent

Exclusion Criteria:

* Age \< 18ans
* Clinical Stage T3 or T4
* Stage N1
* Stage M1
* PSA \> 20
* Gleason Score 8 to 10
* IPSS Score \> 20 alpha-blocking medication.
* Prior pelvic radiotherapy.
* History of active collagenosis (Lupus, Sclerodermia, Dermatomyosis)
* Past history of Inflammatory Bowell Disease
* Bilateral hip prosthesis

Primary outcomes:
measure: GU toxicity analysis (CTCAE)
timeFrame: at baseline, prior treatment
measure: GU toxicity analysis (CTCAE)
timeFrame: at 3 months post-therapy
measure: GU toxicity analysis (CTCAE)
timeFrame: at 6 months post-therapy
measure: GU toxicity analysis (CTCAE)
timeFrame: at 1 year post-therapy
measure: GU toxicity analysis (CTCAE)
timeFrame: at 2 years post-therapy
measure: GU toxicity analysis (CTCAE)
timeFrame: at 3 years post-therapy
measure: GU toxicity analysis (CTCAE)
timeFrame: at 4 years post-therapy
measure: GU toxicity analysis (CTCAE)
timeFrame: at 5 years post-therapy
measure: GI toxicity analysis (CTCAE)
timeFrame: at baseline, prior treatment
measure: GI toxicity analysis (CTCAE)
timeFrame: at 3 months post-therapy
measure: GI toxicity analysis (CTCAE)
timeFrame: at 6 months post-therapy
measure: GI toxicity analysis (CTCAE)
timeFrame: at 1 year post-therapy
measure: GI toxicity analysis (CTCAE)
timeFrame: at 2 years post-therapy
measure: GI toxicity analysis (CTCAE)
timeFrame: at 3 years post-therapy
measure: GI toxicity analysis (CTCAE)
timeFrame: at 4 years post-therapy
measure: GI toxicity analysis (CTCAE)
timeFrame: at 5 years post-therapy
measure: urinary toxicity analysis (IPSS)
timeFrame: at baseline, prior treatment
measure: urinary toxicity analysis (IPSS)
timeFrame: at 3 months
measure: urinary toxicity analysis (IPSS)
timeFrame: at 6 months
measure: urinary toxicity analysis (IPSS)
timeFrame: at 1 year
measure: urinary toxicity analysis (IPSS)
timeFrame: at 2 years
measure: urinary toxicity analysis (IPSS)
timeFrame: at 3 years
measure: urinary toxicity analysis (IPSS)
timeFrame: at 4 years
measure: urinary toxicity analysis (IPSS)
timeFrame: at 5 years
measure: quality of life questionnaires analysis (EPIC26)
timeFrame: baseline, prior treatment
measure: quality of life questionnaires analysis (EPIC26)
timeFrame: at 3 months
measure: quality of life questionnaires analysis (EPIC26)
timeFrame: at 6 months
measure: quality of life questionnaires analysis (EPIC26)
timeFrame: at 1 year
measure: quality of life questionnaires analysis (EPIC26)
timeFrame: at 2 years
measure: quality of life questionnaires analysis (EPIC26)
timeFrame: at 3 years
measure: quality of life questionnaires analysis (EPIC26)
timeFrame: at 4 years
measure: quality of life questionnaires analysis (EPIC26)
timeFrame: at 5 years
measure: sexual function analysis (SHIM)
timeFrame: baseline, prior treatment
measure: sexual function analysis (SHIM)
timeFrame: at 3 months
measure: sexual function analysis (SHIM)
timeFrame: at 6 months
measure: sexual function analysis (SHIM)
timeFrame: at 1 year
measure: sexual function analysis (SHIM)
timeFrame: at 2 years
measure: sexual function analysis (SHIM)
timeFrame: at 3 years
measure: sexual function analysis (SHIM)
timeFrame: at 4 years
measure: sexual function analysis (SHIM)
timeFrame: at 5 years
Secondary outcomes:
measure: Clinical outcomes
timeFrame: at 5 years
measure: Clinical outcomes
timeFrame: at 10 years
Other outcomes:
Locations:
city: Quebec
country: Canada
facility: CHUdeQuebec
Study officials:
affiliation: CHU de Québec
name: Andre-Guy Martin
role: STUDY_CHAIR
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