S0354, Anti-IL-6 Chimeric Monoclonal Antibody in Patients With Metastatic Prostate Cancer That Did Not Respond to Hormone Therapy

OBJECTIVES:

Primary

• Assess the confirmed prostate-specific antigen response in patients with hormone-refractory metastatic prostate cancer treated with anti-IL-6 chimeric monoclonal antibody.

Secondary

• Assess overall survival and progression-free survival of these patients.
• Assess the objective response rate (confirmed and unconfirmed, complete and partial response) in patients with measurable disease treated with this regimen.
• Assess the qualitative and quantitative toxicities of this regimen.

OUTLINE: This is an open-label, multicenter study.

Patients receive anti-IL-6 chimeric monoclonal antibody IV over 2 hours on day 1. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months for up to 2 years.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate

• Metastatic disease (N1 and/or M1)
• Disease unresponsive or refractory to androgen-deprivation therapy
• Must have received only 1 prior chemotherapy regimen comprising a taxane OR mitoxantrone
• Disease progression as defined by one or more of the following:

• Progression of measurable disease

• Prior radiotherapy allowed provided radiotherapy was completed ≥ 2 months ago and lesion progressed since radiotherapy
• Progression of nonmeasurable disease

• Prior radiotherapy within the past 2 months allowed, but disease is considered nonmeasurable
• Rising prostate-specific antigen (PSA) after > 2 courses of chemotherapy OR within 6 months of last chemotherapy dose

• Rising PSA defined as at least 2 consecutive rises in PSA to be documented over a reference value (measure 1)
• PSA ≥ 5 ng/mL
• Surgical or medical castration required

• Castration using luteinizing hormone-releasing hormone agonist (leuprolide acetate or goserelin) or antagonist (abarelix) should not be interrupted
• No history of brain metastases OR currently treated or untreated brain metastases

• Patients with clinical suspicion of brain metastases must have a brain CT scan or MRI negative for metastatic disease within the past 56 days

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-2
• Fertile patients must use effective contraception
• Absolute granulocyte count ≥ 1,500/mm³ (transfusion independent)
• Platelet count ≥ 100,000/mm³ (transfusion independent)
• Hemoglobin ≥ 9 g/dL (transfusion independent)
• Creatinine clearance ≥ 40 mL/min
• Bilirubin ≤ 2 times upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 2 times ULN
• No uncontrolled intercurrent illnesses including, but not limited to, the following:

• Diabetes mellitus
• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• No psychiatric illness or social situation that would preclude study compliance
• No known HIV positivity
• No other prior malignancy except for the following:

• Adequately treated basal cell or squamous cell skin cancer
• Adequately treated stage I or II cancer in complete remission
• Any other cancer from which the patient has been disease-free for 5 years

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 21 days since prior surgery and recovered
• At least 28 days since prior chemotherapy and recovered
• At least 28 days since prior flutamide or ketoconazole
• At least 28 days since prior radiotherapy (to < 30% of the bone marrow only) and recovered

• Prior samarium Sm 153 lexidronam pentasodium allowed
• No prior strontium chloride Sr 89
• At least 42 days since prior bicalutamide or nilutamide
• More than 60 days since prior murine or chimeric proteins or human/murine monoclonal antibody
• Concurrent bisphosphonate therapy allowed provided the following are true:

• Therapy commenced at least 3 weeks ago
• Therapy continues for the entire duration of study treatment
• No other concurrent anticancer therapy, including cytotoxic therapy, biologic therapy, radiotherapy, or hormonal therapy (except for luteinizing hormone-releasing hormone agonist or antagonist in patients who have not had an orchiectomy)