Ultra Hypofractionnated Radiotherapy With HDR Brachytherapy Boost. (HYPO-5)

Laval University

Status: Enrolling

Conditions: Radiotherapy Side Effect; Localized Prostate Carcinoma; Radiotherapy; Hypofractionation; Brachytherapy; Prostate Cancer

Treatments: Radiation: grade and compare reported side effects between groups

Study type: Interventional

Funder types: Other

Identifiers

NCT05786742

HYPO-5

Details and patient eligibility

About

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.

Full 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.

Enrollment: 205 estimated patients

Sex: Male

Ages: 18 to 95 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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205 participants in 2 patient groups

ultra hypo fractionation radiation therapy

Experimental group

Description:

comparative PRO's of 25 Gy in 5 daily fractions (Ultra hypo fractionation) administered to prostate and 1st centimeter of proximal seminal vesicle, starting mid week and ending mid following week.

Treatment:

Radiation: grade and compare reported side effects between groups

moderate hypo fractionation radiation therapy

Active Comparator group

Description:

PRO's of moderate hypo fractionation, 37,5 Gy in 15 or 36 Gy in 12 daily fractions administered 5 days per week.

Treatment:

Radiation: grade and compare reported side effects between groups