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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00433446
Recruitment Status : Completed
First Posted : February 12, 2007
Results First Posted : February 5, 2013
Last Update Posted : February 5, 2013
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Southwest Oncology Group

February 8, 2007
February 12, 2007
November 9, 2012
February 5, 2013
February 5, 2013
April 2007
May 2009   (Final data collection date for primary outcome measure)
Confirmed Prostate-Specific Antigen (PSA) Response [ Time Frame: Assessed every 3 cycles (1 cycle = 14 days) until progression ]
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.
Prostate-specific antigen response
Complete list of historical versions of study NCT00433446 on Archive Site
  • Progression-free Survival (PFS) [ Time Frame: Assessed every 3 cycles (1 cycle = 14 days) until progression ]
    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.
  • Overall Survival (OS) [ Time Frame: 0-3 yeas after registration ]
    Measured from date of registration to date of death due to any cause or last contact
  • Objective Response (Confirmed and Unconfirmed Complete and Partial Response) Among Those Patients With Measurable Disease [ Time Frame: Assessed every 3 cycles (1 cycle= 14 days) of treatment until progression ]
    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.
  • Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug [ Time Frame: Patients were assessed for adverse events after every cycle (1 cycle = 14 days) of protocol treatment ]
    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.
  • Overall survival
  • Progression-free survival
  • Probability of objective response
Not Provided
Not Provided
S0354, Anti-IL-6 Chimeric Monoclonal Antibody in Patients With Metastatic Prostate Cancer That Did Not Respond to Hormone Therapy
A Phase II Study of CNTO 328, A Monoclonal Antibody Against Interleukin-6 (IL-6), in Patients With Hormone Refractory Prostate Cancer

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.



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


  • 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.

Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Prostate Cancer
Biological: CNTO 328
Other Name: anti-IL-6 chimeric monoclonal antibody
Experimental: CNTO 328
Intervention: Biological: CNTO 328
Dorff TB, Goldman B, Pinski JK, Mack PC, Lara PN Jr, Van Veldhuizen PJ Jr, Quinn DI, Vogelzang NJ, Thompson IM Jr, Hussain MH. Clinical and correlative results of SWOG S0354: a phase II trial of CNTO328 (siltuximab), a monoclonal antibody against interleukin-6, in chemotherapy-pretreated patients with castration-resistant prostate cancer. Clin Cancer Res. 2010 Jun 1;16(11):3028-34. doi: 10.1158/1078-0432.CCR-09-3122. Epub 2010 May 18.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
July 2011
May 2009   (Final data collection date for primary outcome measure)


  • 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


  • 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


  • 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)
Sexes Eligible for Study: Male
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
U10CA032102 ( U.S. NIH Grant/Contract )
S0354 ( Other Identifier: SWOG )
Not Provided
Not Provided
Southwest Oncology Group
Southwest Oncology Group
National Cancer Institute (NCI)
Study Chair: Jacek Pinski, MD University of Southern California
Southwest Oncology Group
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP