Evaluation of Late Toxicity Following Intensity-Modulated Radiotherapy and Two Image-Guided Strategies With Corresponding Treatment Margins.

Study Overview
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Brief Summary
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The Calypso® System (Varian Medical Systems, Inc., Palo Alto, CA) is a recent technology using electromagnetic transponders implanted within the prostate. It is a real-time target tracking system that takes into account both inter- and intrafractional target motion. So the exact position and movement of the prostate can be determined during radiation therapy treatment. The aim of this study is to assess pelvic late toxicity rate after intensity-modulated radiotherapy (IMRT) when using the Calypso® System with a reduction of treatment margins. In this randomized study, patients will receive IGRT treatment using the Calypso system or a conventional IGRT treatment.

Detailed Description
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Prostate cancer is the most frequent cancer in men. Radiotherapy is one of the reference treatments for localized prostate cancer. Prostate was initially thought to be a non-moving target, but the newest reports have raised the contrary as evidence. Image-guided radiotherapy (IGRT) is a current standard treatment for localized prostate cancer which enables to take into account interfractional prostate motion before treatment. The Calypso® System (Varian Medical Systems, Inc., Palo Alto, CA) is a recent technology using electromagnetic transponders implanted within the prostate. It is a real-time target tracking system that takes into account both inter- and intrafractional target motion. So the exact position and movement of the prostate can be determined during radiation therapy treatment. As Planned Target Volume (PTV) margins integrate set-up margins and the management of organ motion, margin reduction can reasonably be considered in case of target motion management improvement. To date, no prospective randomized clinical data is available using this technique for the treatment of low- or intermediate-risk prostate cancer patients with modern standard fractionation radiotherapy and image guidance. The aim of this study is to assess pelvic late toxicity rate after intensity-modulated radiotherapy (IMRT) when using the Calypso® System with a reduction of treatment margins. In this randomized study, patients will receive IGRT treatment using the Calypso system or a conventional IGRT treatment.

Official Title
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Randomized Phase II Study Evaluating Late Toxicity Following Intensity-Modulated Radiotherapy and Two Image-Guided Strategies With Corresponding Treatment Margins. (RCMIGI)

Conditions
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Prostate Cancer

Intervention / Treatment
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* Device: Calypso beacon implant
* Radiation: moderate hypofractionation Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Localized prostate cancer, histologically proven. No evidence of metastases (M0). No evidence of lymph nodes involvement (N0) (bilateral lymph node dissection is not mandatory if lymph node involvement risk is low according to the Partin tables). Low-risk or intermediate clinical stage according to the D'Amico classification (T1-T2 and Gleason < 8 and PSA < 20 ng/ml) (appendix 3). No grade > 2 urinary or rectal clinical sign or symptom according to the CTCAE V4.03 scale. Performance status ECOG ≤ 1. No hip prosthesis or metallic vascular graft near the prostate. No endopenian stent. No pace maker, implanted defibrillator or neurostimulator. No allergy to local anesthetics. No irreversible anticoagulation or antiplatelet treatment for the implantation period. Pelvic and abdominal anatomy compatible with the use of the Calypso® system (predictive detector to fiducials distance less than 19 cm, evaluated on planning CT-scan) (distance from skin surface to prostate center less than 17 cm). Patient aged ≥ 18 and less than 80 years old. Dated and signed written informed consent available. Patients must be affiliated to a French Social Security System. Exclusion Criteria: Indication of pelvic nodes irradiation. Prior pelvic irradiation. Biopsy-proven seminal vesicle invasion. Prior bilateral orchiectomy. Prior radical prostatectomy. Other malignancy except adequately-treated basal cell carcinoma of the skin or other malignancy from which the patient has been disease-free for at least 5 years. Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial. Other uncontrolled systemic disease (cardiovascular, renal, liver, pulmonary embolism, etc.). Known VIH positive patients (no specific test needed). Known homozygote ATM Mutation (Ataxia telengiectasia).

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: Image-guided radiation therapy (IGRT) with standard margins<br>moderate hypofractionation during 4 weeks | Radiation: moderate hypofractionation Radiotherapy<br>* moderate hypofractionation Radiotherapy<br>|
| Experimental: Calypso tracking system with margin reduction<br>moderate hypofractionation during 4 weeks after calypso beacon implant 10 days before | Device: Calypso beacon implant<br>* Calypso beacon implant before radiotherapy<br>Radiation: moderate hypofractionation Radiotherapy<br>* moderate hypofractionation Radiotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| assessment of grade > 2 late pelvic toxicities | assessment of grade > 2 late pelvic toxicities between 3 months and 2 years after radiation period | up to 2 years post treatment |