Ultra Hypofractionnated Radiotherapy With HDR Brachytherapy Boost.

Prostate Cancer Clinical Trial

— HYPO-5  

Official title:

ULTRA-HYPO Fractionated (UHF) Compared to Moderate-HYPO Fractionated (MHF) Prostate IGRT With HDR Brachytherapy BOOST : A Phase 1-2 Study.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05786742
• Other study ID #: HYPO-5
• Status: Recruiting
• Phase: N/A
• Start date: April 2014
• Est. completion date: December 2033

Study information

• Verified date: March 2024
• Source: CHU de Quebec-Universite Laval
• Contact: Andre-Guy Martin
• Phone: 14186915264
• Email: andre-guy.martin.med[@]ssss.gouv.qc.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 205
• Est. completion date: December 2033
• Est. primary completion date: June 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 95 Years

Eligibility

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

Related Conditions & MeSH terms

• Brachytherapy
• Hypofractionation
• Prostate Cancer
• Prostatic Neoplasms
• Radiotherapy
• Radiotherapy Side Effect

Intervention

Radiation:
• grade and compare reported side effects between groups
Compare experimental ultra hypo fractionation (25 Gy in 5 daily fractions administered starting mid week and ending mid following week) to our standard fractionation (either 37,5 Gy given in 15 daily fractions, or 36 Gy in 12 daily fractions). 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.

Locations

Country	Name	City	State
Canada	CHUdeQuebec	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
CHU de Quebec-Universite Laval

Country where clinical trial is conducted

Canada, 

References & Publications (19)

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Bachand F, Martin AG, Beaulieu L, Harel F, Vigneault E. An eight-year experience of HDR brachytherapy boost for localized prostate cancer: biopsy and PSA outcome. Int J Radiat Oncol Biol Phys. 2009 Mar 1;73(3):679-84. doi: 10.1016/j.ijrobp.2008.05.003. Ep — View Citation

Crook JM, Gomez-Iturriaga A, Wallace K, Ma C, Fung S, Alibhai S, Jewett M, Fleshner N. Comparison of health-related quality of life 5 years after SPIRIT: Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial. J Clin Oncol. 2011 Feb 1;29( — View Citation

D'Amico AV, Chen MH, Renshaw AA, Loffredo M, Kantoff PW. Androgen suppression and radiation vs radiation alone for prostate cancer: a randomized trial. JAMA. 2008 Jan 23;299(3):289-95. doi: 10.1001/jama.299.3.289. — View Citation

Gregoire JP, Moisan J, Labrecque M, Cusan L, Diamond P. [Validation of a French adaptation of the international prostatic symptom score]. Prog Urol. 1996 Apr;6(2):240-9. French. — View Citation

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Jones CU, Hunt D, McGowan DG, Amin MB, Chetner MP, Bruner DW, Leibenhaut MH, Husain SM, Rotman M, Souhami L, Sandler HM, Shipley WU. Radiotherapy and short-term androgen deprivation for localized prostate cancer. N Engl J Med. 2011 Jul 14;365(2):107-18. d — View Citation

McCammon R, Rusthoven KE, Kavanagh B, Newell S, Newman F, Raben D. Toxicity assessment of pelvic intensity-modulated radiotherapy with hypofractionated simultaneous integrated boost to prostate for intermediate- and high-risk prostate cancer. Int J Radiat — View Citation

Morris WJ, Keyes M, Palma D, Spadinger I, McKenzie MR, Agranovich A, Pickles T, Liu M, Kwan W, Wu J, Berthelet E, Pai H. Population-based study of biochemical and survival outcomes after permanent 125I brachytherapy for low- and intermediate-risk prostate — View Citation

Morris WJ, Keyes M, Spadinger I, Kwan W, Liu M, McKenzie M, Pai H, Pickles T, Tyldesley S. Population-based 10-year oncologic outcomes after low-dose-rate brachytherapy for low-risk and intermediate-risk prostate cancer. Cancer. 2013 Apr 15;119(8):1537-46 — View Citation

Morton G, Loblaw A, Cheung P, Szumacher E, Chahal M, Danjoux C, Chung HT, Deabreu A, Mamedov A, Zhang L, Sankreacha R, Vigneault E, Springer C. Is single fraction 15 Gy the preferred high dose-rate brachytherapy boost dose for prostate cancer? Radiother O — View Citation

Partin AW, Mangold LA, Lamm DM, Walsh PC, Epstein JI, Pearson JD. Contemporary update of prostate cancer staging nomograms (Partin Tables) for the new millennium. Urology. 2001 Dec;58(6):843-8. doi: 10.1016/s0090-4295(01)01441-8. — View Citation

Schmidt MA, Payne GS. Radiotherapy planning using MRI. Phys Med Biol. 2015 Nov 21;60(22):R323-61. doi: 10.1088/0031-9155/60/22/R323. Epub 2015 Oct 28. — View Citation

Stone NN, Stock RG, Cesaretti JA, Unger P. Local control following permanent prostate brachytherapy: effect of high biologically effective dose on biopsy results and oncologic outcomes. Int J Radiat Oncol Biol Phys. 2010 Feb 1;76(2):355-60. doi: 10.1016/j — View Citation

Viani GA, Stefano EJ, Afonso SL. Higher-than-conventional radiation doses in localized prostate cancer treatment: a meta-analysis of randomized, controlled trials. Int J Radiat Oncol Biol Phys. 2009 Aug 1;74(5):1405-18. doi: 10.1016/j.ijrobp.2008.10.091. — View Citation

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* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	GU toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at baseline, prior treatment
Primary	GU toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at 3 months post-therapy
Primary	GU toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at 6 months post-therapy
Primary	GU toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at 1 year post-therapy
Primary	GU toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at 2 years post-therapy
Primary	GU toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at 3 years post-therapy
Primary	GU toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at 4 years post-therapy
Primary	GU toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at 5 years post-therapy
Primary	GI toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at baseline, prior treatment
Primary	GI toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at 3 months post-therapy
Primary	GI toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at 6 months post-therapy
Primary	GI toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at 1 year post-therapy
Primary	GI toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at 2 years post-therapy
Primary	GI toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at 3 years post-therapy
Primary	GI toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at 4 years post-therapy
Primary	GI toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at 5 years post-therapy
Primary	urinary toxicity analysis (IPSS)	median IPSS scores will be reported post-therapy and compare between arms at baseline, prior treatment	at baseline, prior treatment
Primary	urinary toxicity analysis (IPSS)	median IPSS scores will be reported post-therapy and compare between arms at 3 months post-therapy	at 3 months
Primary	urinary toxicity analysis (IPSS)	median IPSS scores will be reported post-therapy and compare between arms at 6 months post-therapy	at 6 months
Primary	urinary toxicity analysis (IPSS)	median IPSS scores will be reported post-therapy and compare between arms at 1 year post-therapy	at 1 year
Primary	urinary toxicity analysis (IPSS)	median IPSS scores will be reported post-therapy and compare between arms at 2 years post-therapy	at 2 years
Primary	urinary toxicity analysis (IPSS)	median IPSS scores will be reported post-therapy and compare between arms at 3 years post-therapy	at 3 years
Primary	urinary toxicity analysis (IPSS)	median IPSS scores will be reported post-therapy and compare between arms at 4 years post-therapy	at 4 years
Primary	urinary toxicity analysis (IPSS)	median IPSS scores will be reported post-therapy and compare between arms at 5 years post-therapy	at 5 years
Primary	quality of life questionnaires analysis (EPIC26)	median EPIC26 scores will be reported post-therapy and compare between arms at baseline, prior treatment	baseline, prior treatment
Primary	quality of life questionnaires analysis (EPIC26)	median EPIC26 scores will be reported post-therapy and compare between arms at 3 months post-treatment	at 3 months
Primary	quality of life questionnaires analysis (EPIC26)	median EPIC26 scores will be reported post-therapy and compare between arms at 6 months post-treatment	at 6 months
Primary	quality of life questionnaires analysis (EPIC26)	median EPIC26 scores will be reported post-therapy and compare between arms at 1 year post-treatment	at 1 year
Primary	quality of life questionnaires analysis (EPIC26)	median EPIC26 scores will be reported post-therapy and compare between arms at 2 years post-treatment	at 2 years
Primary	quality of life questionnaires analysis (EPIC26)	median EPIC26 scores will be reported post-therapy and compare between arms at 3 years post-treatment	at 3 years
Primary	quality of life questionnaires analysis (EPIC26)	median EPIC26 scores will be reported post-therapy and compare between arms at 4 years post-treatment	at 4 years
Primary	quality of life questionnaires analysis (EPIC26)	median EPIC26 scores will be reported post-therapy and compare between arms at 5 years post-treatment	at 5 years
Primary	sexual function analysis (SHIM)	median SHIM scores will be reported at baseline prior treatment	baseline, prior treatment
Primary	sexual function analysis (SHIM)	median SHIM scores will be reported post-therapy and compare between arms at 3 months post-treatment	at 3 months
Primary	sexual function analysis (SHIM)	median SHIM scores will be reported post-therapy and compare between arms at 6 months post-treatment	at 6 months
Primary	sexual function analysis (SHIM)	median SHIM scores will be reported post-therapy and compare between arms at 1 year post-treatment	at 1 year
Primary	sexual function analysis (SHIM)	median SHIM scores will be reported post-therapy and compare between arms at 2 years post-treatment	at 2 years
Primary	sexual function analysis (SHIM)	median SHIM scores will be reported post-therapy and compare between arms at 3 years post-treatment	at 3 years
Primary	sexual function analysis (SHIM)	median SHIM scores will be reported post-therapy and compare between arms at 4 years post-treatment	at 4 years
Primary	sexual function analysis (SHIM)	median SHIM scores will be reported post-therapy and compare between arms at 5 years post-treatment	at 5 years
Secondary	Clinical outcomes	Biochemical disease-free survival has per Phoenix definition (by American Society of Radiation Oncology - ASTRO) will be reported using Kaplan-Meier analysis, as well for disease free survival, metastasis free survival and overall survival.	at 5 years
Secondary	Clinical outcomes	Biochemical disease-free survival has per Phoenix definition (by American Society of Radiation Oncology - ASTRO) will be reported using Kaplan-Meier analysis, as well for disease free survival, metastasis free survival and overall survival.	at 10 years