Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

5 radiation treatments (5 Gy per fraction) to the prostate, seminal vesicle and pelvic nodes given every other day over 2 weeks for a total of 25 Gy.

20-25 radiation treatments (range: 1,8 to 2,15 Gy per fraction) to the prostate, seminal vesicle and pelvic nodes given in 20-25 working day treatments over 4-5 weeks for a total of 43 Gy to 46 Gy.

Assess early and late genito-urinary (GU) toxicities induced assessed via the International Prostate Symptom Score (I-PSS) in the experimental UHF group has compared in a non-inferiority analysis to those of patients who received a standard treatment (control group).

Report and compare changes in a non-inferiority analysis of the International Prostate Symptom Score (I-PSS)

Assess early and late genito-urinary (GU) and gastro-intestinal (GI) toxicities induced and quality of life assessed via expanded prostate cancer index composite (EPIC-26) in the experimental UHF group has compared in a non-inferiority analysis to those of patients who received a standard treatment (control group).

Report and compare changes in a non-inferiority analysis of the expanded prostate cancer index composite" (EPIC-26):

Assess early and late sexual health in the experimental UHF group has compared in a non-inferiority analysis to those of patients who received a standard treatment (control group).

Report and compare changes in a non-inferiority analysis of the Sexual Health Inventory for Men (SHIM)

Assess early and late toxicities reported according to the Common Terminology Criteria for Adverse Events (CTCAE) in the experimental UHF group has compared in a non-inferiority analysis to those of patients who received a standard treatment (control group).

Report and compare changes in a non-inferiority analysis of the toxicities reported according to the Common Terminology Criteria for Adverse Events (CTCAE)

Assess the 5 and 10 years biochemical disease-free survival (bDFS) in the UHF group and compare them for non-inferiority to those of the control group.

Report and compare the biochemical disease free survival (bDFS)

Assess the 5 and 10 years disease-free survival (DFS) in the UHF group and compare them for non-inferiority to those of the control group.

Report and compare the disease free survival (DFS)

Assess the 5 and 10 years metastasis-free survival (MFS) in the UHF group and compare them for non-inferiority to those of the control group.

Report and compare the metastase free survival (MFS)

Assess the 5 and 10 years overall survival (OS) in the UHF group and compare them for non-inferiority to those of the control group.

Report and compare the overall survival (OS)

Andre-Guy Martin, MD MSc FRCPC

Josee Allard

Juanita M Crook, MD, FRCPC

Sarah Rauth, MD,FRCPC

Wayne Koll, MD, FRCPC

Steven Tisseverasinghe, MD, FRCPC

Danny Duplan, MD, FRCPC

Marjory Jolicoeur, MD, FRCPC

Peter Vavassis, MD, FRCPC

Tamim Niazi, MDCM

Marie Duclos, MD

Annie Ebacher, MD

Andre-Guy Martin, MD,MSc,FRCPC

Josée Allard, MSc

Randomized Phase III study, comparing pelvic ultra-hypo fractionated radiotherapy (UHF: 5Gy/fraction) to a standard or moderate hypo-fractionation (1.8-2.15Gy/fraction), both associated to an HDR prostate +/- adjacent seminal vesicles brachytherapy boost (HDR-BT)+ ADT according to NCCN guidelines. Considering that the calculated bio-equivalent doses to the tumor are similar for all treatment options, the UHF technique is deemed to be non-inferior to the standard approach. Treatment acceptability, tolerance and adverse events will be reported and compared for non-inferiority as the primary objective. Secondary objectives are biochemical control, metastasis-free, disease specific and overall survival.

Prostate cancer is the most common non-skin cancer in North American men. In 2020, an estimated 23 300 Canadian men will be diagnosed with prostate cancer of which, 4200 will die. Fortunately, with an early screening, most will have a localized disease at diagnosis. Despite this, high risk disease affects a growing portion of the population and this according to age (29.3%, 39.1%, 60.4%, et 90.6% respectively at 55-59, 65-69, 75-79, \& 85-89 years of age). Gleason score 8 to 10 tumors follow the same pattern (16.5%, 23.4%, 37.2%, and 59.9% at respective ages). Those patients are at risk for harboring lymph nodes metastasis.

Multiple therapeutic options, with similar biochemical disease-free survival (bDFS) are available: surgery +/- salvage radiotherapy +/- androgen deprivation therapy (ADT) or radiotherapy (RT) +/- HDR-BT +/- ADT. For men with high-risk disease, the combined approach of RT + HDR-BT + ADT might even offer higher cancer specific survival (CSS) rates when compared to surgery.

HDR-BT allows for the delivery of a very high (ablative) dose of radiation while giving a lower dose to the nearby organs at risk (OARs). Recently published literature showed that pelvic RT plus HDR-BT significantly increased bDFS (84 vs 77%).

Pelvic RT is generally given on a daily basis (5 days/week) over a period of 4-5 weeks, with 1,8-2,15Gy per fraction. This requires a substantial time investment from patients undergoing treatment. Many studies have shown that prostate cancer offers a radiation cell kill ratio (α/β) of 0.9-1.5 Gy. Furthermore, the most commonly used α/β value for prostate cancer is 1,5 Gy (range 0,8 - 2,2). This low α/β ratio offers a more efficient cell kill with hypo-fractionated doses, offering a better tumor control with a lower cumulative dose, given in a shorter time span. Recently, a multicentric randomized phase III study has shown similar late toxicity and oncologic control outcomes between UHF (\>/= 5 Gy/fraction) and conventionally fractionated RT. However, until now, no phase III study has compared combined UHF pelvic RT to standard fractionation combined with an HDR-BT in this population.

The proposed experimental fractionation scheme for whole pelvic RT in this study will be 5Gy administered every other day over 2 weeks (UHF). It will be compared to standard pelvic RT (1.8-2.15Gy/working day) given over 4 to 5 weeks. Both will be combined with a single 15 Gy fraction of HDR-BT and ADT (goserelin). The UHF treatment modality significantly reduces the overall treatment time, freeing machine-time and allowing more patients to be treated. Given its low α/β ratio, prostate cancer is readily amenable to UHF fractionation. The bio-equivalent dose calculations were done based on published litterature. Neo-adjuvant and adjuvant ADT (goserelin) will be administered for a duration according to NCCN guidelines.

In these COVID-19 pandemic times, a reduction in the number of patients' visits to the clinic is highly desirable in order to limit the risk of virus transmission. UHF would also lower the socio-economic burden incurred by the patients and their families. It also increases the therapeutic efficiency reducing costs for both, patients and health services. The proposed study aims to demonstrate the non-inferiority of UHF treatment compared to standard of care. If this hypothesis is confirmed, all future patients could benefit from it.

In order to improve the quality of life of men diagnosed with prostate cancer this study aim to demonstrate that combined UHF pelvic RT plus HDR-BT (+ ADT according to NCCN guidelines) is safe and non-inferior to standard fractionation regimens in regard to toxicities and tumor control for prostate cancer patients with risk of nodal involvement. Therefore, 500 men will be recruited, in order to confirm the hypothesis.

Pelvic Nodes Ultra-Hypo vs Conventionally Fractionated IMRT With HDR Boost in Prostate Cancer.

Pelvic Nodes Ultra-Hypo Fractionated Versus Conventionally Fractionated IMRT With HDR Brachytherapy Boost in Prostate Cancer: A Collaborative Multi-institutional Non-inferiority Phase 3 Trial. (PCS-XI)

Testosterone blood level, every 3 months for 3 years, every 6 months for 2 years, then annually.

Serum creatinine to evaluate renal function.

List of added medications (name and dosage) needed to alleviate symptoms of potential side effects of therapy and evolution of disease.

Evaluate loss of outcomes (dollars) due to treatment

Tumor extension description if presence of bony metastasis or not (for staging purposes)

Abdominal + Pelvis (thorax not compulsory) for tumor extension description =determination if presence of distant metastasis or not (for staging purposes)

Bone density evaluation to prevent osteoporosis

Recommended but not compulsory - Prostate MRI (tumor description of dominant involved lesion) for determination if presence extension extra capsulary or not.

Optional (tumor extension description if presence of metastasis or not)

Assess early genito-urinary (GU) toxicities induced opposed to baseline assessed via the International Prostate Symptom Score (I-PSS) in the experimental UH group has compared in a non-inferiority analysis to those of patients who received a standard treatment (control group).

Assess early health-related quality of life opposed to baseline assessed via the Expanded Prostate Cancer Index Composite (EPIC-26) in the experimental UH group has compared in a non-inferiority analysis to those of patients who received a standard treatment (control group) every 3 months for 1 year.

Assess late genito-urinary (GU) toxicities induced opposed to baseline evaluated by the International Prostate Symptom Score (I-PSS) in the experimental UH group has compared in a non-inferiority analysis to those of patients who received a standard treatment (control group).

Assess late health-related quality of life opposed to baseline assessed via the Expanded Prostate Cancer Index Composite (EPIC-26) in the experimental UH group has compared in a non-inferiority analysis to those of patients who received a standard treatment (control group) every 6 months up to 36 months, then annually.

Assess early quality of life opposed to baseline assessed via the Sexual Health Inventory for Men (SHIM) in the experimental UH group has compared in a non-inferiority analysis to those of patients who received a standard treatment (control group) every 3 months for 1 year.

Assess early sexual health status opposed to baseline assessed via the Sexual Health Inventory for Men (SHIM) in the experimental UH group has compared in a non-inferiority analysis to those of patients who received a standard treatment (control group) every 6 months up to 36 months, then annually.

Assess early reported toxicities opposed to baseline assessed via the Common Terminology Criteria for Adverse Events (CTCAE) in the experimental UH group has compared in a non-inferiority analysis to those of patients who received a standard treatment (control group) every 3 months for 1 year, every 6 months up to 36 months, then annually.

Assess the 5 years the biochemical disease-free survival (bDFS) in the UH group and compare them for non-inferiority to those of the control group.

Assess the 5 years the disease-free survival (DFS) in the UH group and compare them for non-inferiority to those of the control group.

Assess the 5 years the Metastasis Free Survival (MFS) in the UH group and compare them for non-inferiority to those of the control group.

Assess the 5 years the Overall Survival (OS) in the UH group and compare them for non-inferiority to those of the control group.

Assess the 10 years the biochemical disease-free survival (bDFS) in the UH group and compare them for non-inferiority to those of the control group.

Assess the 10 years the disease-free survival (DFS) in the UH group and compare them for non-inferiority to those of the control group.

Assess the 10 years the Metastasis Free Survival (MFS) in the UH group and compare them for non-inferiority to those of the control group.

Assess the 10 years the Overall Survival (OS) in the UH group and compare them for non-inferiority to those of the control group.

TerSera Therapeutics LLC

CHU de Quebec-Universite Laval

Principal Investigator, M.D., M.Sc., F.R.C.P.C.

Carcinoma

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.

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

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.

grade and compare reported side effects between groups

Andre-Guy Martin

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.

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.

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

Ultra Hypofractionnated Radiotherapy With HDR Brachytherapy Boost.

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

quantitatively evaluated using CTCAE (v5) and compare between arms

median IPSS scores will be reported post-therapy and compare between arms at baseline, prior treatment

median IPSS scores will be reported post-therapy and compare between arms at 3 months post-therapy

median IPSS scores will be reported post-therapy and compare between arms at 6 months post-therapy

median IPSS scores will be reported post-therapy and compare between arms at 1 year post-therapy

median IPSS scores will be reported post-therapy and compare between arms at 2 years post-therapy

median IPSS scores will be reported post-therapy and compare between arms at 3 years post-therapy

median IPSS scores will be reported post-therapy and compare between arms at 4 years post-therapy

median IPSS scores will be reported post-therapy and compare between arms at 5 years post-therapy

median EPIC26 scores will be reported post-therapy and compare between arms at baseline, prior treatment

median EPIC26 scores will be reported post-therapy and compare between arms at 3 months post-treatment

median EPIC26 scores will be reported post-therapy and compare between arms at 6 months post-treatment

median EPIC26 scores will be reported post-therapy and compare between arms at 1 year post-treatment

median EPIC26 scores will be reported post-therapy and compare between arms at 2 years post-treatment

median EPIC26 scores will be reported post-therapy and compare between arms at 3 years post-treatment

median EPIC26 scores will be reported post-therapy and compare between arms at 4 years post-treatment

median EPIC26 scores will be reported post-therapy and compare between arms at 5 years post-treatment

median SHIM scores will be reported at baseline prior treatment

median SHIM scores will be reported post-therapy and compare between arms at 3 months post-treatment

median SHIM scores will be reported post-therapy and compare between arms at 6 months post-treatment

median SHIM scores will be reported post-therapy and compare between arms at 1 year post-treatment

median SHIM scores will be reported post-therapy and compare between arms at 2 years post-treatment

median SHIM scores will be reported post-therapy and compare between arms at 3 years post-treatment

median SHIM scores will be reported post-therapy and compare between arms at 4 years post-treatment

median SHIM scores will be reported post-therapy and compare between arms at 5 years post-treatment

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Pelvic Nodes Ultra-Hypo vs Conventionally Fractionated IMRT With HDR Boost in Prostate Cancer.	NCT05820633	Prostate Cancer Node; Prostate Radiotherapy Si...	Report and comp... Report and comp... Report and comp... Report and comp... Report and comp... Report and comp... Report and comp... Report and comp...	18 Years - 95 Years	CHU de Quebec-Universite Laval
Ultra Hypofractionnated Radiotherapy With HDR Brachytherapy Boost.	NCT05786742	Prostate Cancer Radiotherapy Si... Hypofractionati... Brachytherapy Radiotherapy Localized Prost...	grade and compa...	18 Years - 95 Years	CHU de Quebec-Universite Laval

Spots Global Cancer Trial Database for ultra hypo fractionation