Combination Chemotherapy Followed by Surgery in Treating Patients With Localized Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving chemotherapy before surgery may shrink the tumor so that it can be removed during surgery. PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy followed by surgery in treating patients who have localized prostate cancer.

Detailed Description
-----------------
OBJECTIVES: Determine the 5-year freedom from prostate-specific antigen (PSA) recurrence in patients treated with this regimen. Define the maximum tolerated dose of neoadjuvant docetaxel and mitoxantrone followed by prostatectomy in patients with high-risk localized prostate cancer. (Phase I completed as of 2/15/02) Determine the toxicity of this regimen in these patients. Determine the PSA response rate and pathologic response rate in patients treated with this regimen. Determine the clinical response in patients treated with this regimen. Determine the overall survival of patients treated with this regimen. Determine the surgical margin status at time of prostatectomy in patients treated with this regimen. OUTLINE: This is a dose-escalation study of mitoxantrone. (Phase I completed as of 2/15/02) Patients receive neoadjuvant docetaxel and mitoxantrone weekly on weeks 1-3. Treatment repeats once a week for a total of 4 courses. Patients receive escalating doses of mitoxantrone until the maximum tolerated dose is determined. (Phase I completed as of 2/15/02) Patients undergo prostatectomy 2-4 weeks after completion of neoadjuvant chemotherapy. PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

Official Title
-----------------
Phase I/II Study of Neoadjuvant Weekly Docetaxel and Mitoxantrone Prior to Prostatectomy in Patients With High Risk Localized Prostate Cancer

Conditions
-----------------
Prostate Cancer

Intervention / Treatment
-----------------
* Drug: docetaxel
* Drug: mitoxantrone hydrochloride
* Procedure: conventional surgery


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the prostate High-risk, as defined by 1 of the following: Stage T2b (palpable bilateral involvement) or surgically resectable T3 PSA 15 ng/mL or greater Gleason grade greater than 4+3 (4+3, 4+4, or 5+any, but not 3+4) At least a 50% chance of prostate cancer recurrence within 5 years Planned prostatectomy as primary therapy No evidence of bone metastases by bone scan No evidence of lymph nodes greater than 2 cm on pelvic computed tomography (CT) scan (scan required only if PSA greater than 40 ng/mL) PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Eastern Cooperative Oncology Group(ECOG) 0-2 Life expectancy: At least 10 years Hematopoietic: White Blood Cell(WBC) at least 3,000/mm^3 Neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Conjugated bilirubin no greater than upper limit of normal (ULN) Alkaline phosphatase no greater than 4 times ULN Alanine transaminase(ALT) no greater than 2 times ULN (1.5 times ULN if alkaline phosphatase greater than 2.5 times ULN) Renal: Not specified Cardiovascular: Ejection fraction greater than 50% by Multiple Gated Acquisition(MUGA)scan Other: No other malignancy within the past 5 years except nonmelanoma skin cancer No significant active medical illness that would preclude study therapy No peripheral neuropathy grade 2 or greater No hypersensitivity to drugs formulated with polysorbate-80 No significant contraindications to corticosteroids PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior cytotoxic chemotherapy No other concurrent cytotoxic chemotherapy Endocrine therapy: No prior or concurrent conventional hormonal therapy Radiotherapy: No prior or concurrent radiotherapy (external beam or brachytherapy) Surgery: See Disease Characteristics Other: No prior or concurrent cryotherapy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Docetaxel, Mitoxantrone, Conventional Surgery<br>Drug: Docetaxel-35 mg/m2 i.v. over 15 - 30 minutes will be administered immediately after the mitoxantrone on the same schedule. Drug: Mitoxantrone-Initial dose will be 2 mg/m2 weekly for 3 of every 4 weeks. The dose will then be escalated as described in the dose escalation section up to a maximum dose of 6 mg/m2 weekly for 3 of every 4 weeks. Procedure/Surgery: Conventional Surgery- Prostatectomy will be scheduled 2-4 weeks after the last dose of chemotherapy | Drug: docetaxel<br>* 35 mg/m2 i.v. over 15 - 30 minutes will be administered immediately after the mitoxantrone on the same schedule.<br>Drug: mitoxantrone hydrochloride<br>* Initial dose will be 2 mg/m2 weekly for 3 of every 4 weeks. The dose will then be escalated as described in the dose escalation section up to a maximum dose of 6 mg/m2 weekly for 3 of every 4 weeks.<br>Procedure: conventional surgery<br>* Prostatectomy will be scheduled 2 - 4 weeks after the last dose of chemotherapy.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With 5-year Freedom From Prostate Specific Antigen (PSA) Recurrence. | Number of participants that experienced 5-year freedom from Prostate Specific Antigen (PSA) recurrence (PSA > 0.4 ng/ml confirmed by a second PSA that is higher than the first by any amount (2)) in men with high risk localized prostate cancer treated with neoadjuvant docetaxel/mitoxantrone followed by surgery. | Every 3 months after surgery for up to 5 years. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
adenocarcinoma of the prostate, stage II prostate cancer, stage III prostate cancer