Monoclonal Antibody Therapy in Treating Patients With Prostate Cancer

A Clinical Trial Evaluating The Safety And Efficacy Of ABX-EGF In Patients With Hormone Resistant Prostate Cancer With Elevated PSA Without Metastasis

RATIONALE: Monoclonal antibodies such as ABX-EGF can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: Phase II trial to study the effectiveness of ABX-EGF in treating patients who have prostate cancer that has not responded to hormone therapy.

OBJECTIVES:

• Determine the clinical effect of monoclonal antibody ABX-EGF, determined by the PSA response, in patients with hormone-resistant prostate cancer with rising PSA values without metastasis.
• Determine the pharmacokinetics and safety profile (including immunogenicity) of this drug in these patients.
• Determine the overall survival of patients treated with this drug.
• Determine the time to disease progression and time to PSA progression in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive monoclonal antibody ABX-EGF IV over 1 hour once weekly. Treatment continues every 8 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years.

PROJECTED ACCRUAL: Approximately 30-50 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of prostate cancer with rising PSA values without metastasis

  • PSA must be at least 5 ng/mL
  • PSA must show an increase above a reference level on 2 separate occasions

• Must have tumor over-expressing epidermal growth factor receptor (EGFr) by immunohistochemistry

  • Staining must be 2+ or 3+ in at least 10% of evaluated tumor cells
  • Must have tissue available for diagnostics

• Must have failed prior front-line luteinizing hormone-releasing hormone (LHRH) analogue (e.g., leuprolide or goserelin) OR failed orchiectomy and have castrate levels of testosterone (less than 50 mg/mL) NOTE: Must continue on a LHRH analogue (unless an orchiectomy was performed) throughout the study

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 3 times ULN
• AST and ALT no greater than 3 times ULN

Renal

• Creatinine less then 2.2 mg/dL
• Calcium no greater than ULN

Cardiovascular

• Left ventricular ejection fraction at least 45% by MUGA
• No myocardial infarction within the past year

Other

• HIV negative
• Fertile patients must use effective contraception during and for 1 month after study
• No other malignancy within the past 5 years except basal cell carcinoma
• No history of chronic medical or psychiatric condition or laboratory abnormality that would preclude study participation, administration, or interpretation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• See Disease Characteristics
• At least 6 weeks since prior steroidal or nonsteroidal antiandrogens (4 weeks for flutamide)
• Concurrent steroid therapy allowed as replacement therapy only

Radiotherapy

• Not specified

Surgery

• See Disease Characteristics

Other

• At least 30 days since prior investigational therapy
• At least 30 days since prior anticancer therapy
• No prior systemic therapy for prostate cancer (except hormonal therapy)
• No prior anti-EGFr therapy
• Concurrent antihypercalcemic treatment allowed in the presence of elevated calcium levels but not as cancer therapy for bone disease
• No other concurrent anti-EGFr therapy
• No other concurrent anticancer therapy
• No other concurrent investigational therapy