A Phase I-II Dose Escalation Study of Stereotactic Body Radiation Therapy in Patients With Localized Prostate Cancer

Study Overview
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Brief Summary
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The aim of this study is to test the safety and efficacy of Stereotactic Body Radiation Therapy (SBRT) in localized prostate carcinoma in patients for whom the standard treatment is the irradiation of the entire prostate gland with or without seminal vesicles accompanied or not by hormonal therapy. In light of the accumulating clinical evidence favoring the use of hypo fractionation, SBRT regimen might constitute a much more convenient non-invasive and highly efficient outpatient therapy.

Detailed Description
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Primary objective phase I: To irradiate the prostate gland which might albeit contain microscopic disease with tumoricidal doses of SBRT, and to escalate the dose of SBRT in the visible prostatic tumor towards the best tumoricidal dose without exceeding the normal tissue tolerance and toxicity in patients with organ confined T2-T3 N0 prostate carcinoma. Primary objective phase II: To determine the rate of acute toxicity grade 2 or more defined as toxicity occurring immediately after the first fraction of radiotherapy and up to 90 days after the start of radiotherapy treatment. Secondary objectives phase II: To determine efficacy measured by PSA failure using Phoenix definition. To determine long-term late toxicity (>90 days after treatment start). Exploratory endpoint phase II: • To determine the feasibility of achieving dose constraints in the organs at risk using high technology radiotherapy.

Official Title
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A Phase I-II Dose Escalation Study of Stereotactic Body Radiation Therapy in Patients With Localized Prostate Cancer

Conditions
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Prostate Adenocarcinoma

Intervention / Treatment
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* Radiation: Stereotactic Body Radiation Therapy (SBRT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients must be willing and capable to provide informed consent Histologic confirmation of prostate adenocarcinoma T2-T3 tumors, N0 (clinically by no evidence of metastatic lymph nodes on CT or MRI) No direct evidence of regional or distant metastases PSA less than or equal to 50 μg/ml Visible gross tumor at the prostate endorectal coil MRI. The ultrasound or MRI based volume estimation of the patient's prostate gland no greater than 70g or 70cc No significant urinary obstructive symptoms; IPSS score must be ≤ 15 (alpha blockers allowed) Patient must have undergone an endorectal coil magnetic resonance image (MRI) of the prostatic gland (before rectal spacer if any), Patient must have undergone the following assessments in case of PSA ≥ 20μg/L, and/or T3 tumor and/or Gleason Score ≥ 8: bone scan Chest abdominal and pelvis computed tomography (CT) scan If tumor is localized at less than 3 mm from the rectum a rectal spacer is mandatory. Patient accepts the rectal spacer to be injected before treatment starts Patient accepts to have one planning MRI after the injection of rectal spacer (without endorectal coil) Patient accepts the preparation of the bladder (bladder full), before the planning MRI, planning CT and then before each treatment fraction Exclusion Criteria: Previous radiotherapy in the pelvis Tumor localized at less than 3 mm from the urethra History of inflammatory colitis (including Crohn's disease and ulcerative colitis) Prior cancer in the pelvis Any 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 inclusion in the trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase I (dose escalation)/ Phase II<br>Phase I Prostate tumor: starting dose 9 Gy per fraction in 5 fractions (total 45 Gy) and subsequent dose escalation up to 10 Gy. Prostate gland: fixed prophylactic tumoricidal dose 7.25 Gy per fraction in 5 fractions (no dose escalation). Total 36.25 Gy. Phase II Additional patients will be treated at either the maximum tolerated dose (MTD) or at the highest dose level as determined by the investigators from the Phase I portion of the study. | Radiation: Stereotactic Body Radiation Therapy (SBRT)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (phase I) | Observation of dose-limiting toxicities (DLT) defined as any treatment-related grade ≥ 3 acute toxicity occurring in the radiation field or irradiated volumes in the following categories GI or GU. In addition, any other grade 4 or 5 toxicity attributed to the therapy constitutes a DLT. | During the first 30 days from the start of treatment | 
| Toxicity (phase II) | Acute GU and GI toxicity (grade 2 or more) according to the NCI CTCAE v4.0. | 90 days after the first fraction of radiotherapy treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy (phase II) | PSA failure using Phoenix definition | 3 monthly assessments during the first 2 years and 6 monthly assessments until end of study (5 years) | 
| Toxicity (phase II) | Long term GU and GI toxicity (grade 2 or more) according to the NCI CTCAE v4.0. | > 90 days and up to 5 years from the start of protocol treatment |