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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer; Localized Prostate Carcinoma; Radiotherapy Side Effect; Radiotherapy; Brachytherapy; Hypofractionation
• Intervention / Treatment: Radiation: grade and compare reported side effects between groups

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.

• Study Type: Interventional
• Enrollment (Estimated): 205
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Andre-Guy Martin; Phone Number: 14186915264; Email: andre-guy.martin.med@ssss.gouv.qc.ca
• Study Contact Backup: Name: Josee Allard; Phone Number: 14186915264; Email: josee.allard@chudequebec.ca

Study Locations

• Canada
  • Quebec, Canada, G1R 2J6
    • Recruiting
    • CHUdeQuebec
    • Contact: Andre-Guy Martin, MD,MSc,FRCPC; Phone Number: 1-418-691-5264; Email: Andre-Guy.Martin@mail.chuq.qc.ca
    • Contact: Josée Allard, MSc; Phone Number: 16730 1-418-691-5264; Email: Josee.Allard@chuq.qc.ca
    • Principal Investigator: Andre-Guy Martin, MD,MSc,FRCPC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ultra hypo fractionation radiation therapy; 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.	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.; Other Names: report and compare IPSS scores; report and compare EPIC26 scores; report and compare SHIM scores; report and compare CTCAE scores; report and compare clinical outcomes
Active Comparator: moderate hypo fractionation radiation therapy; PRO's of moderate hypo fractionation, 37,5 Gy in 15 or 36 Gy in 12 daily fractions administered 5 days per week.	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.; Other Names: report and compare IPSS scores; report and compare EPIC26 scores; report and compare SHIM scores; report and compare CTCAE scores; report and compare clinical outcomes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GU toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at baseline, prior treatment
GU toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at 3 months post-therapy
GU toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at 6 months post-therapy
GU toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at 1 year post-therapy
GU toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at 2 years post-therapy
GU toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at 3 years post-therapy
GU toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at 4 years post-therapy
GU toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at 5 years post-therapy
GI toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at baseline, prior treatment
GI toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at 3 months post-therapy
GI toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at 6 months post-therapy
GI toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at 1 year post-therapy
GI toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at 2 years post-therapy
GI toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at 3 years post-therapy
GI toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at 4 years post-therapy
GI toxicity analysis (CTCAE)	quantitatively evaluated using CTCAE (v5) and compare between arms	at 5 years post-therapy
urinary toxicity analysis (IPSS)	median IPSS scores will be reported post-therapy and compare between arms at baseline, prior treatment	at baseline, prior treatment
urinary toxicity analysis (IPSS)	median IPSS scores will be reported post-therapy and compare between arms at 3 months post-therapy	at 3 months
urinary toxicity analysis (IPSS)	median IPSS scores will be reported post-therapy and compare between arms at 6 months post-therapy	at 6 months
urinary toxicity analysis (IPSS)	median IPSS scores will be reported post-therapy and compare between arms at 1 year post-therapy	at 1 year
urinary toxicity analysis (IPSS)	median IPSS scores will be reported post-therapy and compare between arms at 2 years post-therapy	at 2 years
urinary toxicity analysis (IPSS)	median IPSS scores will be reported post-therapy and compare between arms at 3 years post-therapy	at 3 years
urinary toxicity analysis (IPSS)	median IPSS scores will be reported post-therapy and compare between arms at 4 years post-therapy	at 4 years
urinary toxicity analysis (IPSS)	median IPSS scores will be reported post-therapy and compare between arms at 5 years post-therapy	at 5 years
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
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
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
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
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
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
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
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
sexual function analysis (SHIM)	median SHIM scores will be reported at baseline prior treatment	baseline, prior treatment
sexual function analysis (SHIM)	median SHIM scores will be reported post-therapy and compare between arms at 3 months post-treatment	at 3 months
sexual function analysis (SHIM)	median SHIM scores will be reported post-therapy and compare between arms at 6 months post-treatment	at 6 months
sexual function analysis (SHIM)	median SHIM scores will be reported post-therapy and compare between arms at 1 year post-treatment	at 1 year
sexual function analysis (SHIM)	median SHIM scores will be reported post-therapy and compare between arms at 2 years post-treatment	at 2 years
sexual function analysis (SHIM)	median SHIM scores will be reported post-therapy and compare between arms at 3 years post-treatment	at 3 years
sexual function analysis (SHIM)	median SHIM scores will be reported post-therapy and compare between arms at 4 years post-treatment	at 4 years
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: CHU de Quebec-Universite Laval
• Investigators: Study Chair: Andre-Guy Martin, CHU de Québec

Publications and helpful links

General Publications

• 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(4):362-8. doi: 10.1200/JCO.2010.31.7305. Epub 2010 Dec 13.
• 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. Epub 2008 Oct 27.
• Grimm P, Billiet I, Bostwick D, Dicker AP, Frank S, Immerzeel J, Keyes M, Kupelian P, Lee WR, Machtens S, Mayadev J, Moran BJ, Merrick G, Millar J, Roach M, Stock R, Shinohara K, Scholz M, Weber E, Zietman A, Zelefsky M, Wong J, Wentworth S, Vera R, Langley S. Comparative analysis of prostate-specific antigen free survival outcomes for patients with low, intermediate and high risk prostate cancer treatment by radical therapy. Results from the Prostate Cancer Results Study Group. BJU Int. 2012 Feb;109 Suppl 1:22-9. doi: 10.1111/j.1464-410X.2011.10827.x.
• 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 cancer. Urology. 2009 Apr;73(4):860-5; discussion 865-7. doi: 10.1016/j.urology.2008.07.064. Epub 2009 Jan 24.
• 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. doi: 10.1002/cncr.27911. Epub 2012 Dec 26.
• 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 Oncol. 2011 Sep;100(3):463-7. doi: 10.1016/j.radonc.2011.08.022. Epub 2011 Sep 14.
• Wright JL, Izard JP, Lin DW. Surgical management of prostate cancer. Hematol Oncol Clin North Am. 2013 Dec;27(6):1111-35, vii. doi: 10.1016/j.hoc.2013.08.010.
• 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.ijrobp.2009.01.078. Epub 2009 Jul 23.
• 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.
• Holm HH, Gammelgaard J. Ultrasonically guided precise needle placement in the prostate and the seminal vesicles. J Urol. 1981 Mar;125(3):385-7. doi: 10.1016/s0022-5347(17)55044-2. No abstract available.
• Hill RP, Rodemann HP, Hendry JH, Roberts SA, Anscher MS. Normal tissue radiobiology: from the laboratory to the clinic. Int J Radiat Oncol Biol Phys. 2001 Feb 1;49(2):353-65. doi: 10.1016/s0360-3016(00)01484-x.
• Williams MV, Denekamp J, Fowler JF. A review of alpha/beta ratios for experimental tumors: implications for clinical studies of altered fractionation. Int J Radiat Oncol Biol Phys. 1985 Jan;11(1):87-96. doi: 10.1016/0360-3016(85)90366-9.
• 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 Oncol Biol Phys. 2009 Oct 1;75(2):413-20. doi: 10.1016/j.ijrobp.2008.10.050. Epub 2009 Apr 11.
• 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.
• Arcangeli G, Saracino B, Gomellini S, Petrongari MG, Arcangeli S, Sentinelli S, Marzi S, Landoni V, Fowler J, Strigari L. A prospective phase III randomized trial of hypofractionation versus conventional fractionation in patients with high-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2010 Sep 1;78(1):11-8. doi: 10.1016/j.ijrobp.2009.07.1691. Epub 2010 Jan 4.
• 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.
• 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. doi: 10.1056/NEJMoa1012348.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2014
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): December 1, 2033

Study Registration Dates

• First Submitted: December 23, 2022
• First Submitted That Met QC Criteria: March 14, 2023
• First Posted (Actual): March 28, 2023

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: brachytherapy; hypo fractionation; Ultra Hypo fractionation
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: HYPO-5

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No