Androgen Suppression and Radiation With/Out Docetaxel in High-Risk Localized Prostate Cancer

Study Overview
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Brief Summary
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RATIONALE: Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as flutamide, bicalutamide, leuprolide, buserelin, and goserelin, may lessen the amount of androgens made by the body. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving androgen suppression therapy together with radiation therapy is more effective with or without docetaxel in treating prostate cancer. PURPOSE: This randomized phase III trial is studying androgen suppression therapy, radiation therapy, and docetaxel to see how well they work compared with androgen suppression therapy and radiation therapy in treating patients with high-risk localized prostate cancer. CLOSURE: This trial closed to further accrual in November 2009. The study endpoints will not be reached.

Detailed Description
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OBJECTIVES: Primary To compare disease-free survival rates in patients with high-risk localized adenocarcinoma of the prostate treated with androgen suppression therapy and radiotherapy with vs without docetaxel. Secondary To compare overall survival. To compare time to biochemical disease progression. To compare time to local disease progression. To compare time to distant disease progression. To compare time to next anticancer therapy. To compare progression-free survival. To compare degree of prostate-specific antigen (PSA) suppression prior to radiotherapy. To compare quality of life (QOL) using EORTC QLQ C30 and EORTC QLQ PR25 questionnaires and a trial-specific checklist. To compare the nature, severity, and frequency of adverse events. OUTLINE: This is a multicenter study. Patients are stratified according to Gleason score (≤ 7 vs ≥ 8), baseline prostate-specific antigen (PSA) (> 20 ng/mL vs ≤ 20 ng/mL), and participating center. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive androgen suppression therapy comprising oral flutamide three times daily or oral bicalutamide once daily for 4 weeks AND leuprolide subcutaneously (SC) or intramuscularly every 1-6 months, buserelin SC every 2 or 3 months, or goserelin SC every 1 or 3 months for 3 years. Patients also receive docetaxel IV over 60 minutes on day 1. Treatment with docetaxel repeats every 21 days for up to 4 courses. Beginning at least 4 weeks after completion of chemotherapy, patients undergo pelvic radiotherapy once daily 5 days a week for up to 8 weeks. Arm II: Patients receive androgen suppression therapy and undergo pelvic radiotherapy as in arm I. Patients complete quality of life questionnaires at baseline, periodically during treatment, and then every 6 months for 5 years. After completion of study treatment, patients are followed at 3 and 6 months, every 6 months for 5 years, and then annually thereafter.

Official Title
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A Phase III Study of Neoadjuvant Docetaxel and Androgen Suppression Plus Radiation Therapy Versus Androgen Suppression Alone Plus Radiation Therapy for High-Risk Localized Adenocarcinoma of the Prostate

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: bicalutamide
* Drug: buserelin
* Drug: flutamide
* Drug: goserelin
* Drug: leuprolide acetate
* Procedure: neoadjuvant therapy
* Procedure: quality-of-life assessment
* Radiation: radiation therapy
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the prostate Localized (N0, M0) disease No small cell or transitional cell carcinoma in the biopsy specimen Considered to be at high risk for recurrence based on the presence of at least one of the following adverse prognostic features: T stage ≥ 3a Gleason score ≥ 8 Baseline prostate-specific antigen (PSA) > 20 ng/mL Deemed to be an appropriate candidate for chemotherapy, as assessed by a medical oncologist Negative pelvic and para-aortic lymph nodes on CT scan or MRI of the abdomen and pelvis Any lymph node appearing ≥ 1.5 cm on CT scan or MRI must be histologically negative by either needle aspirate or lymph node dissection No metastases by chest x-ray and bone scan PATIENT CHARACTERISTICS: ECOG performance status 0-1 Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 10.0 g/dL AST and/or ALT ≤ 1.5 times upper limit of normal (ULN) Alkaline phosphatase ≤ 2.5 times ULN Total bilirubin normal Serum creatinine ≤ 1.5 times ULN Able (i.e., sufficiently fluent) and willing to complete the quality of life questionnaires in either English or French Fertile patients must use effective contraception No history of other malignancies, except adequately treated nonmelanoma skin cancer or other curatively treated solid tumor with no evidence of disease for > 5 years No serious non-malignant disease resulting in a life expectancy of < 10 years No known hypersensitivity to any study medications No existing peripheral neuropathy ≥ grade 2 No bilateral hip replacement prostheses No contraindication to pelvic radiotherapy including, but not limited to, inflammatory bowel disease or severe bladder irritability No medical condition that would contraindicate the study treatment regimen, including severe respiratory insufficiency, uncontrolled diabetes, or severe hypertension No other serious illness or psychiatric or medical condition that would preclude management of the patient according to the study, including active uncontrolled infection or significant cardiac dysfunction PRIOR CONCURRENT THERAPY: Prior androgen suppression therapy allowed provided it was initiated no more than 4 weeks prior to study entry At least 4 weeks since prior 5-alpha-reductase inhibitors (e.g., finasteride) for benign prostatic hypertrophy No prior cytotoxic anticancer therapy No prior chemotherapy for carcinoma of the prostate No prior surgical treatment for carcinoma of the prostate, except transurethral resection or bilateral orchiectomy No prior pelvic radiotherapy No concurrent nilutamide No other concurrent investigational drugs No other concurrent anticancer therapy (cytotoxic therapy, biologic/immunotherapy, or radiotherapy)

Ages Eligible for Study
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Minimum Age: 18 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: Antiandrogen; LHRH; Docetaxel, Radiation Therapy<br>Antiandrogen (Flutamide or Bicalutamide) LHRH agonist (Eligard) Docetaxel | Drug: bicalutamide<br> <br> Drug: buserelin<br> <br> Drug: flutamide<br> <br> Drug: goserelin<br> <br> Drug: leuprolide acetate<br> <br> Procedure: neoadjuvant therapy<br> <br> Procedure: quality-of-life assessment<br> <br> Radiation: radiation therapy<br>* 46 Gy in 23 fractions over < 5 weeks. Boost: 24-28 Gy in 12-14 fractions over < 3 weeks<br>Drug: Docetaxel<br> <br> |
| Active Comparator: Antiandrogen; LHRH; Radiation Therapy<br>Antiandrogen (Flutamide or Bicalutamide) LHRH agonist (Eligard) | Drug: bicalutamide<br> <br> Drug: buserelin<br> <br> Drug: flutamide<br> <br> Drug: goserelin<br> <br> Drug: leuprolide acetate<br> <br> Procedure: neoadjuvant therapy<br> <br> Procedure: quality-of-life assessment<br> <br> Radiation: radiation therapy<br>* 46 Gy in 23 fractions over < 5 weeks. Boost: 24-28 Gy in 12-14 fractions over < 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  |  | 
| Time to biochemical disease progression |  |  | 
| Time to local disease progression |  |  | 
| Time to distant disease progression |  |  | 
| Time to next anti-cancer therapy |  |  | 
| Progression-free survival |  |  | 
| Degree of prostate-specific antigen (PSA) suppression prior to radiotherapy |  |  | 
| Quality of life |  |  | 
| Adverse events |  |  | 

 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 II prostate cancer, stage III prostate cancer, stage IV prostate cancer