Stereotactic Body Radiation Therapy in Treating Patients With Prostate Cancer

Study Overview
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Brief Summary
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RATIONALE: Stereotactic body radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue. PURPOSE: This phase I/II trial is studying the side effects and best dose of stereotactic body radiation therapy and to see how well it works in treating patients with prostate cancer.

Detailed Description
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OBJECTIVES: Primary To escalate the dose of stereotactic body radiotherapy (SBRT) to a tumoricidal dose without exceeding the maximum tolerated dose in patients with organ-confined prostate cancer. (Phase I) To determine the late, severe grade 3-5 genitourinary and gastrointestinal toxicity occurring between 270-540 days (i.e., 9-18 months) from the start of the protocol treatment as assessed by CTCAE v3.0. (Phase II) Secondary To determine the dose-limiting toxicity of SBRT in these patients. (Phase I) To determine the 2-year biochemical (PSA) control (freedom from PSA failure), disease-free and overall survival, local control, freedom from distant metastases, and the incidence of high-grade adverse events of any type in patients treated with this therapy in order to determine if the therapy is promising enough for further clinical investigation. (Phase II) OUTLINE: This is a multicenter, phase I dose-escalation study followed by a phase II open-label study. Phase I: Patients undergo 5 treatments of stereotactic body radiotherapy (SBRT). Phase II: Patients undergo SBRT at the maximum tolerated dose as in phase I. After completion of study treatment, patients are followed at 1.5, 3, 6, 9, and 12 months, every 6 months for 5 years, and then once a year for years 5-10. PROJECTED ACCRUAL: A total of 97 patients will be accrued for this study.

Official Title
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A Phase I and II Study of Stereotactic Body Radiation Therapy (SBRT) for Low and Intermediate Risk Prostate Cancer (SBRT Prostate)

Conditions
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Prostate Cancer

Intervention / Treatment
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* Radiation: stereotactic body radiation therapy (SBRT)- 45 Gy
* Radiation: stereotactic body radiation therapy (SBRT) - 47.5 Gy
* Radiation: stereotactic body radiation therapy (SBRT) - 50 Gy (Phase 1)
* Radiation: stereotactic body radiation therapy (SBRT) - 50 Gy (Phase 2)


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the prostate Stage T1a, T1b, T1c disease Stage T2a or T2b No direct evidence of regional or distant metastases No T2c, T3, or T4 tumors Gleason score ≤ 7 Must meet the following criteria: Prostate-specific antigen (PSA) ≤ 20 ng/mL prior to starting hormonal therapy (if given) for patients with a Gleason score of 2-6 PSA ≤ 15 ng/mL prior to starting hormonal therapy (if given) for patients with a Gleason score of 7 Risk of pelvic lymph node involvement < 20% according to Roach formula Ultrasound-based volume estimation of the prostate gland ≤ 60 g PATIENT CHARACTERISTICS: Zubrod performance status 0-2 Fertile patients must use effective contraception No prior invasive malignancy, except for nonmelanoma skin cancer, unless disease-free for a minimum of 3 years (e.g., carcinoma in situ of the breast, oral cavity, or cervix are allowed) No significant urinary obstructive symptoms American Urological Association (AUA) score of ≤ 15 (alpha blockers allowed) No history of inflammatory colitis (including Crohn disease and ulcerative colitis) No history of significant psychiatric illness No severe, active comorbidity including any of the following: Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months Transmural myocardial infarction within the past 6 months Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days prior to registration Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects Laboratory tests for liver function and coagulation parameters are not required for entry into this protocol AIDS (based on current CDC definition) or other immunocompromising condition HIV testing is not required for entry into this protocol PRIOR CONCURRENT THERAPY: See Disease Characteristics More than 9 months since prior hormonal therapy as neoadjuvant therapy or to downsize the prostate gland No prior pelvic radiotherapy No prior chemotherapy or surgery for prostate cancer No prior transurethral resection of the prostate (TURP) or cryotherapy to the prostate No plans for other concurrent post-treatment, adjuvant, antineoplastic therapy including surgery, cryotherapy, conventionally fractionated radiotherapy, hormonal therapy, or chemotherapy as part of the treatment for prostate cancer

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1: Stereotactic Body Radiation Therapy (SBRT) 45 Gy<br>The Phase 1 portion of the study will have a 3+3 design. The dose of SBRT is escalated - 45 Gy | Radiation: stereotactic body radiation therapy (SBRT)- 45 Gy<br>* Dose of SBRT - 45 Gray (Gy) in five fractions<br>|
| Experimental: Phase 1: Stereotactic Body Radiation Therapy (SBRT)- 47.5 Gy<br>The Phase 1 portion of the study will have a 3+3 design. The dose of SBRT is escalated- 47.5 Gy | Radiation: stereotactic body radiation therapy (SBRT) - 47.5 Gy<br>* Dose of SBRT - 47.5 Gray (Gy) in five fractions<br>* Other names: Dose of SBRT - 47.5 Gy in five fractions;|
| Experimental: Phase 1: Stereotactic Body Radiation Therapy (SBRT)- 50 Gy<br>The Phase 1 portion of the study will have a 3+3 design. The dose of SBRT is escalated- 50 Gy | Radiation: stereotactic body radiation therapy (SBRT) - 50 Gy (Phase 1)<br> <br> * Other names: Dose of SBRT - 50 Gray (Gy) in five fractions;|
| Experimental: Phase 2: Stereotactic Body Radiation Therapy (SBRT)- 50 Gy<br>The dose of SBRT is escalated - 50 Gy in Phase 2 | Radiation: stereotactic body radiation therapy (SBRT) - 50 Gy (Phase 2)<br> <br> * Other names: Dose of SBRT - 50 Gray (Gy) in five fractions;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Dose Limiting Toxicity (Phase 1 Only) | Dose-limiting toxicity (DLT) was defined as grade 3 to 5 GI, genito urinary, sexual, or neurologic toxicity attributed to therapy occurring within 90 days of registration using Common Terminology Criteria of Adverse Events(version 3) | 90 days after start of treatment | 
| No. of Late Severe GU Toxicity (for Phase 2 Only) | To determine late severe GU toxicity defined as grade 3-5 occurring between 279-540 days (i.e., 9-18 months) from the start of protocol treatment. Toxicity was defined using the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0. CTCAE uses a range of grades from 1 to 5; 1 - Mild 2 - Moderate 3 - Severe 4 - Life-threatening 5 - Death. | 18 months | 
| No. of Late Severe GI Toxicity (for Phase 2 Only) | To determine late severe GI toxicity defined as grade 3-5 occurring between 279-540 days (i.e., 9-18 months) from the start of protocol treatment. Toxicity was defined using the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0. CTCAE uses a range of grades from 1 to 5; 1 - Mild 2 - Moderate 3 - Severe 4 - Life-threatening 5 - Death. | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GU Toxicity (Only Phase 2) | To determine acute severe GU toxicity is defined as grade 3-5 occurring prior to 270 days from the start of the protocol treatment. Toxicity was defined using the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0. CTCAE uses a range of grades from 1 to 5; 1 - Mild 2 - Moderate 3 - Severe 4 - Life-threatening 5 - Death. | 9 months from start of treatment | 
| GI Toxicity | To determine acute severe GI toxicity is defined as grade 3-5 occurring prior to 270 days from the start of the protocol treatment. Toxicity was defined using the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0. CTCAE uses a range of grades from 1 to 5; 1 - Mild 2 - Moderate 3 - Severe 4 - Life-threatening 5 - Death. | 9 months from start of treatment | 
| Non-GU Toxicity | To determine non-GU (genitourinary) toxicity is defined as grade 3-5. Toxicity was defined using the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0. CTCAE uses a range of grades from 1 to 5; 1 - Mild 2 - Moderate 3 - Severe 4 - Life-threatening 5 - Death. | 60 months | 
| Non-GI Toxicity | To determine non-GI (gastrointestinal) toxicity is defined as grade 3-5. Toxicity was defined using the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0. CTCAE uses a range of grades from 1 to 5; 1 - Mild 2 - Moderate 3 - Severe 4 - Life-threatening 5 - Death. | 60 months | 
| Freedom From Biochemical Failure | Biochemical failure RTOG (Radiation Therapy Oncology Group)-ASTRO (American Society for Therapeutic Radiology and Oncology) definition (also known as Phoenix definition). Thus, when the PSA rises by more than 2 ng/ml above the lowest level (nadir) achieved after treatment, biochemical failure has occurred and the date of the failure is recorded at the time the nadir plus 2 ng/ml level is reached. | 36 months | 
| Overall Survival | The survival time will be measured from the date of accession to the date of death. | 60 months | 
| Disease Specific Survival | Disease-Specific Survival Disease-specific survival will be measured from the date of study entry to the date of death due to prostate cancer as the percentage of participants who survived the prostrate cancer disease. | 60 months | 
| Clinical Progression Including Local/Regional and Distant Relapse | Clinical progression including local/regional and distant relapse is measured using Kaplan-Meier method | 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the prostate, stage I prostate cancer, stage IIB prostate cancer, stage IIA prostate cancer