RATIONALE: Testosterone can stimulate the growth of prostate cancer cells. Hormone therapy using leuprolide may fight prostate cancer by reducing the production of testosterone. Some tumors become resistant to hormone therapy. Alternating short schedules of testosterone and leuprolide combined with a chemotherapy drug, such as docetaxel, may reduce resistance to the hormone therapy and kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving testosterone and leuprolide together with docetaxel works in treating patients with recurrent or metastatic adenocarcinoma of the prostate (prostate cancer).

Condition	Treatment or Intervention	Phase
adenocarcinoma of the prostate recurrent prostate cancer stage IV prostate cancer	Drug: docetaxel  Drug: leuprolide  Drug: testosterone  Procedure: androgen therapy  Procedure: chemotherapy  Procedure: endocrine therapy  Procedure: hormone therapy  Procedure: releasing factor agonist therapy  Procedure: steroid therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the efficacy of rapid hormonal cycling with testosterone and leuprolide in combination with docetaxel, in terms of obtaining a durable decline in prostate-specific antigen level or reduction of abnormal sites of disease, in patients with recurrent or non-castrate metastatic adenocarcinoma of the prostate.

Secondary

• Determine the safety of this regimen in these patients.
• Determine the antitumor effects and changes in measurable disease in patients treated with this regimen.
• Determine the affects of testosterone administration on CYP3A activity and docetaxel pharmacokinetics in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to clinical state (rising prostate-specific antigen vs non-castrate metastatic disease).

Patients receive leuprolide intramuscularly and docetaxel IV over 1 hour on day 1 and testosterone gel topically on days 22-28. Treatment repeats every 28 days for 6 courses* in the absence of disease progression or unacceptable toxicity.

NOTE: *Testosterone gel is applied only during courses 1-5.

Patients are followed monthly for 1 year and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 76 patients (38 per stratum) will be accrued for this study within approximately 2 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate in either of the following clinical states:
• History of localized disease with prior definitive radiotherapy or surgery
• Biochemically progressive disease*
• No radiographically evident disease
• Radiographically evident non-castrate metastatic disease at the time of diagnosis or after treatment for localized disease
• Radiographically (new osseous lesions or more than a 25% increase in a bidimensionally measurable tumor mass) AND/OR biochemically progressive disease*
• Testosterone greater than 180 mg/dL
• No active CNS or epidural tumor NOTE: *Biochemically progressive disease, defined as an increase of at least 50% in the prostate-specific antigen (PSA) level across at least 3 determinations each measured more than 2 weeks apart with a baseline PSA of at least 2 ng/mL

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• At least 3 months

Hematopoietic

• WBC at least 3,500/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin greater than 8.0 g/dL

Hepatic

• Bilirubin normal
• SGOT and SGPT less than 2.5 times upper limit of normal (ULN) AND alkaline phosphatase less than ULN OR
• Alkaline phosphatase no greater than 4 times ULN AND SGPT and SGOT less than ULN

Renal

• Creatinine no greater than 1.6 mg/dL OR
• Creatinine clearance at least 60 mL/min

Cardiovascular

• No New York Heart Association class III or IV cardiac disease

Pulmonary

• No severe debilitating pulmonary disease

Other

• Fertile patients must use effective contraception during and for at least 6 months after study treatment
• No uncontrolled serious active infection
• No grade 2 or greater peripheral neuropathy
• No prior severe hypersensitivity reaction to drugs formulated with polysorbate 80

PRIOR CONCURRENT THERAPY: Biologic therapy

• No concurrent immunotherapy

Chemotherapy

• No prior chemotherapy
• No other concurrent chemotherapy

Endocrine therapy

• Prior hormonal therapy before radiotherapy or radical prostatectomy allowed provided the total duration of therapy is no more than 6 months
• No more than 1 course of intermittent hormonal therapy up to a maximum exposure of 6 months

Radiotherapy

• See Disease Characteristics
• No concurrent therapeutic radiotherapy

Surgery

• See Disease Characteristics

Other

• At least 7 days since prior inhibitors or inducers of CYP3A, including the following:
• Fluconazole
• Itraconazole
• Macrolide antibiotics (e.g., azithromycin, clarithromycin, erythromycin, and troleanodomycin)
• Midazolam
• Nifedipine
• Uncaria tomentosa (cat's claw)
• Chamomile (matricaria chamomila)
• Echinacea
• Hydrastis canadensis (Goldenseal)
• Glycyrrhiza glabra (licorice)
• Milk thistle
• Trifolium pratense (wild cherry)
• Garlic
• No concurrent inhibitors or inducers of CYP3A during courses 1 and 2
• No concurrent administration of the following drugs:
• Phenytoin
• Carbamazepine
• Barbiturates
• Rifampin
• Phenobarbital
• Hypericum perforatum (St. John's wort)
• Ketoconazole
• No other concurrent experimental anticancer medication

Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231,  United States; Recruiting
New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting

Study chairs or principal investigators

Howard I. Scher, MD,  Principal Investigator,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000331936; MSKCC-03076; NCT00070369
Record last reviewed:  September 2003
Last Updated:  March 21, 2005
Record first received:  October 3, 2003
ClinicalTrials.gov Identifier:  NCT00070369
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08