S9921, Hormone Therapy With or Without Mitoxantrone and Prednisone in Patients Who Have Undergone Radical Prostatectomy for Prostate Cancer

Study Overview
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Brief Summary
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RATIONALE: Hormones can stimulate the production of prostate cancer cells. Hormone therapy may fight prostate cancer by reducing the production of androgens. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether hormone therapy plus mitoxantrone and prednisone is more effective than hormone therapy alone for prostate cancer. PURPOSE: This randomized phase III trial is studying hormone therapy, mitoxantrone, and prednisone to see how well they work compared to hormone therapy alone in treating patients who have undergone radical prostatectomy for prostate cancer.

Detailed Description
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OBJECTIVES: Compare the overall and disease-free survival of patients with high-risk adenocarcinoma of the prostate treated with adjuvant androgen deprivation therapy with or without mitoxantrone and prednisone after radical prostatectomy. Compare the qualitative and quantitative toxic effects of these regimens in this patient population. Compare the prostate-specific antigen (PSA) progression-free survival rate in patient treated with these regimens. Determine whether PSA progression is a surrogate endpoint for survival or disease-free survival in this patient population. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to surgical extent of disease (organ confined vs not organ confined, but N0 vs N1), Gleason's sum (less than 7 vs 7 vs greater than 7), and planned radiotherapy (yes vs no). Patients are randomized to one of two treatment arms. Arm I:Patients receive goserelin subcutaneously once every 13 weeks (8 injections total) and oral bicalutamide once daily for 2 years in the absence of disease progression or unacceptable toxicity. Arm II:Patients receive mitoxantrone IV over 30 minutes on day 1 and oral prednisone twice daily on days 1-21. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive hormonal therapy as in arm I beginning concurrently with the initiation of mitoxantrone and prednisone. Patients may undergo radiotherapy 5 days a week for 6.5-7.8 weeks beginning anytime (arm I) or after completion of chemotherapy (arm II), at the discretion of the physician, in the absence of disease progression or unacceptable toxicity. Patients are offered the possibility to participate in biomarker research by allowing their tissue/blood to be studied. Patients are followed every 6 months for 2 years and then annually for up to 13 years. PROJECTED ACCRUAL: A total of 1,360 patients (680 per treatment arm) will be accrued for this study within 9.5 years.

Official Title
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Adjuvant Androgen Deprivation Versus Mitoxantrone Plus Prednisone Plus Androgen Deprivation in Selected High-Risk Prostate Cancer Patients Following Radical Prostatectomy

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: bicalutamide
* Drug: goserelin
* Drug: mitoxantrone hydrochloride
* Drug: prednisone


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed stage T1-T3 adenocarcinoma of the prostate before radical prostatectomy and lymph node dissection Must have undergone prostatectomy within the past 120 days Must meet at least 1 of the following pathologic criteria: Gleason sum at least 8 pT3b (seminal vesicle), pT4, or N1 Gleason sum of 7 and positive margin Preoperative PSA greater than 15 ng/mL, Gleason score greater than 7, or PSA level greater than 10 ng/mL and Gleason score greater than 6 Must have an undetectable PSA (no greater than 0.2 ng/mL) documented after surgery or prior to adjuvant hormonal therapy (for patients initiating adjuvant hormonal therapy prior to study) No evidence of metastatic disease on bone scan if PSA is 20 ng/mL or greater at clinical diagnosis No distant metastatic disease PATIENT CHARACTERISTICS: Performance status: SWOG 0-1 Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Cardiovascular: No uncontrolled congestive heart failure If history of cardiac disease, LVEF at least 50% by MUGA scan or 2-D echocardiogram Other: No HIV positivity No other prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or stage I or II cancer that is currently in complete remission PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Not specified Endocrine therapy: Prior neoadjuvant hormonal therapy of no more than 4 months duration before radical prostatectomy allowed Other concurrent adjuvant hormonal therapy allowed if initiated prior to study Concurrent low-dose megestrol (less than 40 mg/day) for hot flashes allowed Radiotherapy: No prior radiotherapy No concurrent whole pelvis irradiation Concurrent radiotherapy allowed at the discretion of the physician Surgery: See Disease Characteristics See Endocrine therapy Recovered from prior surgery Other: No other prior or concurrent therapy for adenocarcinoma of the prostate

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: bicalutamide, goserelin<br>androgen deprivation | Drug: bicalutamide<br> <br> * Other names: Casodex;Drug: goserelin<br> <br> * Other names: Zoladex;|
| Experimental: bicalutamide, goserelin, mitoxantrone, prednisone<br>androgen deprivation plus mitoxantrone, prednisone | Drug: bicalutamide<br> <br> * Other names: Casodex;Drug: goserelin<br> <br> * Other names: Zoladex;Drug: mitoxantrone hydrochloride<br> <br> Drug: prednisone<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Measured from date of randomization to date of death from any cause. Patient known to be alive are censored at date of last contact. | at 10 Years | 
| Disease Free Survival | Measured from date of randomization to date of first observation of recurrence or death due to any cause. Patients without recurrence are censored at date of last contact. | at 10 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare Qualitative and Quantitative Toxicities of These Regimens in These Patients | Number of patients with adverse events that are related to study drug | Up to 22 months from registration | 
| PSA Progression Free Survival | Measured from date of randomization to date of PSA progression or death due to any cause. PSA progression is defined as a serum PSA level of > 0.2 ng/mL measured on 3 consecutive occasions or in the absence of increasing PSA, a positive bone scan result or other radiographic or histologic evidence of progression will be used. Date of progression will be the date that the first measure of increasing PSA is noted in the series of 3. | Up to 10 Years | 
| PSA Progression as Surrogate Endpoint for Overall Survival or Disease Free Survival |  | Up to 10 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 II prostate cancer, stage III prostate cancer