Post-operative or Early Salvage XRT and ADT for High Risk PCa

Study Overview
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Brief Summary
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RATIONALE: Conformal radiation therapy uses a 3-dimensional (3-D) image of the tumor to help focus thin beams of radiation directly on the tumor. Giving conformal external-beam radiation therapy in higher doses over a shorter period of time may kill more tumor cells and have fewer side effects. Androgens can cause the growth of prostate cancer cells. Hormone therapy, such as leuprolide acetate, may lessen the amount of androgens made by the body. It is not yet known whether radiation therapy is more effective when given together with or without hormone therapy in treating patients with prostate cancer who have undergone surgery. PURPOSE: This randomized phase III trial is studying radiation therapy to see how well it works compared with radiation therapy given together with hormone therapy in treating patients who have undergone surgery for stage I, stage II, or stage III prostate cancer.

Detailed Description
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OBJECTIVES: To investigate the potential benefit of post-operative radiotherapy with vs without a combined and adjuvant treatment consisting of short-term androgen suppression for improving the biochemical progression-free survival of patients who have undergone radical prostatectomy for stage I-III prostate cancer. OUTLINE: This is a multicenter study. Patients are stratified according to institution, pathological stage (pT2R1 vs pT3R0 vs pT3R1), Gleason sum (≤ 3+4 vs ≥ 4+3), and WHO performance status (0 vs 1). Within 3 months after radical surgery, patients are randomized to 1 of 2 treatment arms. Arm I: Patients undergo post-operative conformal external beam irradiation for 6.5 weeks. Arm II: Beginning between days -5 to -3, patients receive an antiandrogen for 2-4 weeks. Beginning on day 0, patients receive leuprolide acetate subcutaneously once (6-month depot) and undergo conformal external beam irradiation 5 times weekly for 6.5 weeks. Patients undergo quality of life assessments periodically. After completion of study treatment, patients are followed up every 6 months for 5 years and then yearly thereafter.

Official Title
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Immediate or Early Salvage Post-operative External Radiotherapy Combined With Concomitant and Adjuvant Hormonal Treatment Versus Immediate or Early Salvage Postoperative External Radiotherapy Alone in pT3a-b R0-1 cN0M0 / pT2R1 cN0M0, Gleason Score 5-10 Prostatic Carcinoma. A Phase III Study

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: antiandrogen therapy
* Drug: leuprolide acetate
* Radiation: 3-dimensional conformal radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of prostate cancer Clinical stage cT1-2-3a, N0, M0 disease pre-operatively Pre-operative PSA ≤ 5 x upper limit of normal Presenting the following conditions after radical prostatectomy: Gleason sum 5-10 Pathologic stage pT2R1 (positive surgical margins with at least a tumor trans-section > 2 mm) or pT3a-b (irrespective of margin status) Negative lymph node (LN) status (pN0) by LN sampling or LN dissection Unknown pathological LN status is not allowed, except for disease classified as cT ≤ cT1c with baseline PSA ≤ 10 ng/mL, Gleason score < 7, and ≥ 12 positive core biopsies < 50% Undetectable post-operative PSA within 3 months of surgery PATIENT CHARACTERISTICS: WHO performance status 0-1 WBC ≥ 3 x 10^9/L Hemoglobin ≥ 110 g/L Platelet count ≥ 100 x 10^9/L No 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 No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule PRIOR CONCURRENT THERAPY: See Disease Characteristics More than 5 years since prior chemotherapy No prior pelvic irradiation No prior bilateral orchiectomy No prior hormonal treatment except neoadjuvant treatment lasting ≤ 3 months No other concurrent anticancer agent or modality

Ages Eligible for Study
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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: Arm I<br>Patients undergo post-operative conformal external beam irradiation for 6.5 weeks. | Radiation: 3-dimensional conformal radiation therapy<br>* Undergo radiotherapy<br>|
| Experimental: Arm II<br>Beginning on day -5 to -3, patients receive an antiandrogen for 2-4 weeks. Beginning on day 0, patients receive leuprolide acetate subcutaneously once (6-month depot) and undergo conformal external beam irradiation 5 times weekly for 6.5 weeks. | Drug: antiandrogen therapy<br>* Given systemically<br>Drug: leuprolide acetate<br>* Given subcutaneously<br>Radiation: 3-dimensional conformal radiation therapy<br>* Undergo radiotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical progression-free survival |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical progression-free survival |  |  | 
| Distant-metastases-free survival |  |  | 
| Overall survival |  |  | 
| Quality of life as assessed by QLQ-C30 and QLQ-PR25 at baseline and at 6 months, 1 year, 2 years, and 5 years after treatment |  |  | 
| Acute and late toxicity according to NCI CTCAE version 3.0 |  |  | 

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