Radiation Therapy and Hormone Therapy in Treating Patients With Prostate Cancer

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high energy x-rays to damage tumor cells. Hormone therapy combined with radiation therapy may be a more effective treatment for prostate cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of four different combinations of radiation and hormone therapy in treating patients with prostate cancer.

Detailed Description
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OBJECTIVES: I. Examine whether total androgen suppression (TAS) with flutamide/goserelin and whole-pelvic irradiation followed by a cone-down boost to the prostate improves progression-free survival at 5 years by at least 10% compared to TAS and prostate-only irradiation in patients with adenocarcinoma of the prostate at significant risk of nodal involvement. II. Examine whether induction and concurrent (neoadjuvant) TAS and radiotherapy improves the progression-free survival at 5 years by at least 10% compared to adjuvant TAS and radiotherapy. III. Compare treatments with regard to local control, time to distant failure, and overall survival. OUTLINE: Randomized study. Arm I: Neoadjuvant Antiandrogen Therapy with Radiotherapy. Flutamide, FLUT, NSC-147834; Goserelin, Zoladex, ZDX, NSC-606864; with irradiation of the whole pelvis followed by a boost to the prostate using photons of at least 6 MV. Arm II: Neoadjuvant Antiandrogen Therapy with Radiotherapy; FLUT; ZDX; with irradiation of the prostate using equipment as in Arm I. Arm III: Radiotherapy followed by Adjuvant Antiandrogen Therapy. Irradiation as in Arm I; followed by FLUT; ZDX. Arm IV: Radiotherapy followed by Adjuvant Antiandrogen Therapy. Irradiation as in Arm II; followed by FLUT; ZDX. PROJECTED ACCRUAL: 1,200 patients will be accrued over 2.5 years.

Official Title
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A PHASE III TRIAL COMPARING WHOLE PELVIC IRRADIATION FOLLOWED BY A CONEDOWN BOOST TO BOOST IRRADIATION ONLY AND COMPARING NEOADJUVANT TO ADJUVANT TOTAL ANDROGEN SUPPRESSION (TAS)

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: flutamide
* Drug: goserelin acetate
* Radiation: low-LET photon therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the prostate Any stage with an estimated risk of node involvement at least 15% (and therefore at significant risk for local and/or systemic failure) based on pretreatment PSA and Gleason score (GS), e.g.: GS of 7 and PSA greater than 7.5 ng/mL GS of 6 and PSA greater than 22.5 ng/mL GS of 5 and PSA greater than 37.5 ng/mL PSA greater than 4 and less than 100 ng/mL Highest pretreatment value determined by a monoclonal assay that has a normal range of 0-4 ng/mL PSA measured by polyclonal assay (e.g., Yang) that has a normal range of 0-2.5 ng/mL may need to be divided by a conversion factor of approximately 1.5 GS determination required prior to entry No distant metastases No biopsy proven lymph node involvement Ineligible for protocol RTOG-9408 (clinical stages T2c-T4 with GS of 6 or higher are eligible for this study) PATIENT CHARACTERISTICS: Age: Any age Performance status: Karnofsky 70-100% Hematopoietic: Not specified Hepatic: Liver function tests no greater than 1.2 times normal Renal: Not specified Other: No major medical or psychiatric illness that would prevent completion of treatment or interfere with follow-up No second malignancy within 5 years except superficial nonmelanomatous skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy Endocrine therapy: At least 90 days since testosterone At least 60 days since finasteride Radiotherapy: No prior radiotherapy Surgery: No more than 60 days since surgical staging No radical surgery or cryosurgery

Ages Eligible for Study
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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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Neoadjuvant total androgen suppression (TAS) given 2 months before and during radiation therapy (RT) to the whole pelvis followed by a prostate boost. | Drug: flutamide<br>* Drug used for TAS.<br>Drug: goserelin acetate<br>* Drug used for TAS.<br>Radiation: low-LET photon therapy<br>* radiation therapy<br>* Other names: radiation therapy;|
| Experimental: Arm 2<br>Neoadjuvant TAS given 2 months before and during RT to the prostate only. | Drug: flutamide<br>* Drug used for TAS.<br>Drug: goserelin acetate<br>* Drug used for TAS.<br>Radiation: low-LET photon therapy<br>* radiation therapy<br>* Other names: radiation therapy;|
| Experimental: Arm 3<br>RT to the whole pelvis followed by a boost to the prostate followed by 4 months of TAS. | Drug: flutamide<br>* Drug used for TAS.<br>Drug: goserelin acetate<br>* Drug used for TAS.<br>Radiation: low-LET photon therapy<br>* radiation therapy<br>* Other names: radiation therapy;|
| Experimental: Arm 4<br>RT to the prostate only followed by 4 months of TAS. | Drug: flutamide<br>* Drug used for TAS.<br>Drug: goserelin acetate<br>* Drug used for TAS.<br>Radiation: low-LET photon therapy<br>* radiation therapy<br>* Other names: radiation therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (Arms 1, 3 vs. Arms 2, 4) |  | From randomization to the first occurrence of biochemical failure, clinical failure (local or distant), death from any cause, or last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (Arms 1, 2 vs. Arms 3, 4) |  | From randomization to the first occurrence of biochemical failure, clinical failure (local or distant), death from any cause, or last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. | 
| Local progression |  | From randomization to the date of local progression or last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. | 
| Distant metastasis |  | From randomization to the date of metastatic disease or last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. | 
| Overall survival |  | From the date of randomization to the date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. | 

 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, stage III prostate cancer, stage IV prostate cancer