Hypofractionated Radiotherapy Versus Stereotactic Irradiation With Hyaluronic Acid

Study Overview
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Brief Summary
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The present randomized, open, multicentric Phase II trial, in parallel groups with two arms of treatment, compares the treatment A, moderate hypofractionated radiotherapy of 62Gy, to treatment B, stereotactic irradiation of 37.5 Gy with hyaluronic acid injection in the space between the prostate and the rectum to preserve the rectal-wall from high doses of irradiation. The study aims to assess the rates of late urinary toxicities of grade ≥ 2 induced by a moderate hypofractionated radiotherapy (62Gy in 20 fractions of 3.1Gy) and by a stereotactic radiotherapy (37.5Gy in 5 fractions of 7.5Gy), and the rectal toxicities after an injection of hyaluronic acid between the rectal wall and the prostate. Ninety-six patients and 9 centers are included in the protocol.

Official Title
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Moderate Hypofractionated Radiotherapy (62 Gy in 20 Fractions of 3.1 Gy) Versus Stereotactic Radiotherapy (37.5 Gy in 5 Fractions of 7.5 Gy) With Hyaluronic Acid Injection Between the Prostate and the Rectum for Prostate Cancer of Low- to Intermediate Risk; RPAH2

Conditions
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Prostatic Adenocarcinoma

Intervention / Treatment
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* Radiation: Moderate hypofractionated radiotherapy
* Radiation: Stereotactic radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age superior or equal to 18 years and inferior to 80 years. patient with a low- to intermediate-risk prostate cancer, according to D'Amico classification, for an exclusive irradiation. prostate cancer histologically proven. performance index OMS (World Health Organization) of grade 0-2. indication of external beam radiotherapy validate by the medical commission of the institution. IPSS (International Prostate Symptom Score < 15/35 (without alpha-blocker). the signed consent form. Exclusion Criteria: Rectal surgery antecedents. prostate resection less than 6 mois. Involvement of the seminal vesicles or of the capsule on MRI. patient who can't cooperate during the treatment. pelvic irradiation antecedents. antecedents of inflammatory intestinal pathologies. neoplasia. patients treated with anti-neoplastic or anti-angiogenic or with other treatments used in rheumatology and which may include methotrexate (in order not to have a radiosensitizing effect). patients receiving anticoagulant treatment. other undergoing study that may interfere with the present study. patient under legal protection measure. hypersensitivity to hyaluronic acid. patient with auto-immune disease. patient receiving immunosuppressive medication. severe allergies. history of endocarditis.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Moderate Hypofractionated radiotherapy (62Gy)<br>20 fractions of 3.1Gy | Radiation: Moderate hypofractionated radiotherapy<br>* Moderate hypofractionated radiotherapy of 62Gy in 20 fraction of 3.1Gy.<br>|
| Experimental: Stereotactic radiotherapy (37.5Gy)<br>5 fractions of 7.5Gy) | Radiation: Stereotactic radiotherapy<br>* Stereotactic radiotherapy of 37.5Gy in 5 fraction of 7.5Gy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with late urinary toxicities of grade ≥ 2 after moderate hypofractionated radiotherapy (62Gy in 20 fractions of 3.1Gy) and after stereotactic radiotherapy (37.5Gy in 5 fractions of 7.5Gy). | Late urinary toxicities of grade ≥ 2 assessed using the Common Toxicity Criteria for Adverse Effects ( CTCAE) v 4.0 classification from 3 months to 3 years. | Follow-up at ≥ 3 months after the radiotherapy and up to 3 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival rates without biological relapse in both arms. | Survival rates without biological relapse (increase of the PSA (prostate-specific antigen) beyond nadir + 2 ng/ml, using Phoenix definition). | 3 years. | 
| Evaluation and comparison of the acute urinary and rectal toxicities in both arms. | all toxicities will be listed using Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0. | 3 months: evaluation at 3 months. | 
| Evaluation and comparison of the sexual preservation rates in both arms. | evaluation and comparison of the sexual preservation rates in both arms using International Index of Erectile Function (IIEF). | 3 years. | 
| Late rectal toxicities in both arms, for the evaluation of the hyaluronic acid efficacy to preserve the rectal wall in both approaches. | Late rectal toxicities in both arms, for the evaluation of the hyaluronic acid efficacy to preserve the rectal wall in both approaches, using Common Toxicity Criteria for Adverse Effects (CTCAE) 4.0. | 3 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spacer, Rectal and bladder toxicities, Prostate, Hypofractionated radiotherapy, Stereotactic irradiation