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

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as anti-IL-6 chimeric monoclonal antibody, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. PURPOSE: This phase II trial is studying how well anti-IL-6 chimeric monoclonal antibody works in treating patients with metastatic prostate cancer that did not respond to hormone therapy.

Detailed Description
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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.

Official Title
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A Phase II Study of CNTO 328, A Monoclonal Antibody Against Interleukin-6 (IL-6), in Patients With Hormone Refractory Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Biological: CNTO 328


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CNTO 328<br> | Biological: CNTO 328<br> <br> * Other names: anti-IL-6 chimeric monoclonal antibody;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed Prostate-Specific Antigen (PSA) Response | PSA response is defined as a 50% reduction in accordance with the recommendations of the orginal PSA Working Group. Confirmed PSA response is defined as PSA response at two or more time points at least 4 weeks apart, without objective disease progression or symptomatic deterioration. | Assessed every 3 cycles (1 cycle = 14 days) until progression | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | PFS is defined as tumor progression by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, PSA progression by PSA Working Group criteria, or symptomatic deterioration. | Assessed every 3 cycles (1 cycle = 14 days) until progression | 
| Overall Survival (OS) | Measured from date of registration to date of death due to any cause or last contact | 0-3 yeas after registration | 
| Objective Response (Confirmed and Unconfirmed Complete and Partial Response) Among Those Patients With Measurable Disease | Complete Response (CR) is a complete disappearance of all measurable and non-measurable disease. No new lesions. No disease related symptoms. PSA = .2 ng/ml. Partial Response (PR) applies only to patients with at least one measurable lesion. Greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. | Assessed every 3 cycles (1 cycle= 14 days) of treatment until progression | 
| Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal. | Patients were assessed for adverse events after every cycle (1 cycle = 14 days) of protocol treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the prostate, stage IV prostate cancer, recurrent prostate cancer