Trastuzumab and Docetaxel in Treating Patients Who Have Metastatic Prostate Cancer That Is Refractory to Hormone Therapy

OBJECTIVES:

• Compare the efficacy and toxicity of docetaxel (arm I) vs trastuzumab (Herceptin) (arm II), followed by a combination of docetaxel and trastuzumab in patients with androgen-independent or hormone-refractory metastatic, Her2/neu-positive prostate cancer. (Arm I closed to accrual effective 07/30/2001.)

OUTLINE: This is a multicenter study.

• Arm I: Patients receive docetaxel IV over 1 hour weekly for 6 weeks. Treatment continues every 8 weeks for at least 2 courses in the absence of unacceptable toxicity. (Arm I closed to accrual effective 07/30/2001. Arm I patients crossover to arm II.)
• Arm II: Patients receive trastuzumab (Herceptin) IV over 30-90 minutes weekly for 8 weeks. Treatment continues every 8 weeks for at least 2 courses in the absence of unacceptable toxicity.

Patients with progressive or stable disease after 2 courses of single-agent therapy receive docetaxel IV over 1 hour on day 1 of each week for 6 consecutive weeks and trastuzumab IV over 30-90 minutes on day 1 of each week for 8 consecutive weeks. Treatment continues every 8 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity.

Patients with complete or partial response to single-agent therapy continue on that therapy until experiencing progressive or stable disease. The patients then proceed to combination therapy.

Patients are followed until death.

PROJECTED ACCRUAL: A total of 108-160 patients (54-80 per treatment arm) will be accrued for this study. (Arm I closed to accrual effective 07/30/2001.)

DISEASE CHARACTERISTICS:

• Histologically confirmed stage IV prostate cancer (any T, any N, M1, any G; D3)
• Clinical evidence of metastatic disease in bone or soft tissue
• Her2/neu-positive (2+ and 3+) by immunochemistry or fluorescent in situ hybridization
• Androgen-independent

• Serum PSA at least 10 ng/mL that has risen on 3 successive evaluations after prior hormonal therapy
• At least 1 month since prior antiandrogen therapy (e.g., flutamide, bicalutamide, or nilutamide) and rising PSA levels with 1 of the 2 rising PSA levels, measured at least 2 weeks apart, after antiandrogen withdrawal
• Bone only disease and elevated PSA alone allowed
• LHRH analog therapy must continue in patients who have not had prior orchiectomy and have castrate levels of testosterone

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• SWOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• WBC at least 3,500/mm3
• Absolute granulocyte count at least 1,800/mm3
• Platelet count at least lower limit of normal (LLN)

Hepatic:

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• SGOT no greater than 2 times ULN

Renal:

• Creatinine no greater than 1.6 mg/dL
• Creatinine clearance at least 50 mL/min

Cardiovascular:

• Ejection fraction more than 50% or more than LLN by MUGA scan or 2-D echocardiogram
• No symptomatic coronary artery disease
• No active ischemia on EKG

Other:

• Fertile patients must use effective contraception
• No other prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent biologic therapy

Chemotherapy:

• No more than one prior nonanthracycline chemotherapy regimen (including suramin)

Endocrine therapy:

• See Disease Characteristics
• No concurrent corticosteroids as antiemetic

Radiotherapy:

• At least 4 weeks since prior radiotherapy
• At least 3 months since prior strontium chloride Sr 89 and recovered
• No concurrent radiotherapy to measurable lesions

Surgery:

• See Disease Characteristics