Clinical trial NCT00385827: A Safety and Efficacy Study of Siltuximab (CNTO 328) in Male Subjects With Metastatic Hormone-Refractory Prostate Cancer (HRPC)
Official title: A Phase 2, Multicenter, Open-Label Study of CNTO 328 (Anti-IL-6 Monoclonal Antibody) in Combination With Mitoxantrone Versus Mitoxantrone in Subjects With Metastatic Hormone-Refractory Prostate Cancer (HRPC)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cancer, Prostate
Keywords: Cancer
Prostate
IL-6
Mitoxantrone
Metastatic prostate cancer
Lead sponsor: Centocor, Inc.
Sponsor class: INDUSTRY
First posted: 2006-10-11
Enrollment: 106
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety and efficacy of siltuximab administered in combination with mitoxantrone and prednisone in participants with metastatic (spread of cancer cells from one part of the body to another) hormone-refractory (not responding to treatment) prostate cancer (abnormal tissue that grows and spreads in the body) (HRPC).

Detailed description: This is a 2-part, open-label (all people know the identity of the intervention) multicenter (when more than 1 hospital or medical school team work on a medical research study), Phase 2 study to evaluate the safety and efficacy of the combination of siltuximab plus mitoxantrone versus mitoxantrone in participants with metastatic HRPC who have received 1 prior Docetaxel-based chemotherapy (treatment of disease, usually cancer, by chemical agents) regimen (pattern of giving treatment). Part 1 of the study is single arm where participants will receive mitoxantrone, prednisone and siltuximab. Part 2 of the study is randomized portion (the study drug is assigned by chance), consisting of 2-arms. The experimental arm will consist of treatment with mitoxantrone, prednisone and siltuximab. The control arm will consist of treatment with mitoxantrone and prednisone. Mitoxantrone will be administered at a dose of 12 milligram per square meter (mg/m\^2) intravenously (into a vein) as a 30-minute infusion (a fluid or a medicine delivered into a vein by way of a needle) on Day 1 of each 3-week cycle, until disease progression or unacceptable toxicity (any harmful effect of a drug) or up to 10 cycles (a maximum total dose of approximately 120 mg/m\^2). Siltuximab will be administered at a dose of 6 mg/kilogram intravenously as a 2-hour infusion, starting Day 1 of Cycle 1 to continue every 2 weeks until disease progression or unacceptable toxicity or up to a maximum of 1 year. All participants will receive prednisone 5 mg twice daily starting with the first administration of Mitoxantrone. The duration of treatment will be a maximum of 12 months for cumulative dose. Radiologic assessments will be performed on Week 12 after the first study agent dosing, then every 9 weeks until the end of treatment and then once every 3 months until documented disease progression. Tumor (a mass in a specific area) response will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. There will be short-term follow-up visits (conducted monthly for 2 months), followed by long-term follow-up visits (conducted once every 3 months). Participants' safety will also be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Histologically (the study of tissue under the microscope) or cytologically (the study of cells) confirmed adenocarcinoma (a malignant epithelial tumor with a glandular organization) of the prostate
* Radiologically (Gamma and Computed Topography \[CT\] scans) documented metastatic disease
* At least 6 weeks of treatment with 1 prior docetaxel-based chemotherapy for metastatic Hormone Refractory Prostate Cancer (HRPC)
* Disease progression, during or within 6 months of stopping of prior docetaxel-based therapy, based on one of the following: serum Prostate Specific Antigen (PSA) progression, defined as a rise in at least 2 consecutive serum PSA values, each obtained at least 1 week apart or radiologic disease progression: if disease progression is shown by bone scan only, then disease progression is defined by the appearance of 2 or more new bone lesions (abnormal area of tissue, such as a wound, sore, rash, or boil)
* Orchiectomy (surgery to remove one or both testicles) or testosterone less than 50 nanogram per decilliter (ng/dL) by means of pharmacological/chemical castration

Exclusion Criteria:

* No evidence of a brain tumor
* No more than 1 line of chemotherapy for metastatic prostate cancer
* No prior mitoxantrone treatment
* Prior malignancy (other than prostate cancer) except adequately treated superficial bladder cancer, basal cell or squamous cell carcinoma (type of cancer) of the skin, or other cancer for which the subject has been disease-free for atleast 3 years
* No Human Immunodeficiency Virus (HIV) (a life-threatening infection that you can get from an infected person's blood or from having sex with an infected person) seropositivity or hepatitis (inflammation of the liver) B or C infection

Primary outcomes:
measure: Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to 12 weeks after last dose administration
measure: Part 2: Progression Free Survival (PFS)
timeFrame: Randomization, Week 12, then every 9 weeks until 1 month after last dose administration, then every 3 months until disease progression or death, up to 2 years
Secondary outcomes:
measure: Time to Clinical Deterioration (TtCD)
timeFrame: Start of treatment (Part 1)/Randomization (Part 2), Week 1 of each cycle up to 1 month after last dose administration, and thereafter every 3 months until clinical deterioration or death, up to 2 years
measure: Number of Participants With Palliative Response
timeFrame: Start of treatment (Part 1)/Randomization (Part 2), Week 1 of each cycle up to 1 month after last dose administration, and thereafter every 3 months up to 2 years
measure: Number of Participants With Prostate Specific Antigen (PSA) Response
timeFrame: Start of treatment (Part 1)/Randomization (Part 2), Week 1 of each cycle up to 1 month after last dose administration, and thereafter every 3 months until disease progression, up to 2 years
measure: Overall Survival (OS)
timeFrame: Start of treatment (Part 1)/Randomization (Part 2) until death, up to 2 years
Other outcomes:
Locations:
city: Norwalk
country: United States
state: Connecticut
city: Port Saint Lucie
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Shreveport
country: United States
state: Louisiana
city: Baltimore
country: United States
state: Maryland
city: Saint Louis
country: United States
state: Missouri
city: New York
country: United States
state: New York
city: Philadelphia
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: N Charleston
country: United States
state: South Carolina
city: Milwaukee
country: United States
state: Wisconsin
city: Innsbruck
country: Austria
city: St Veit An Der Glan
country: Austria
city: Wels N/A
country: Austria
city: Wien
country: Austria
city: Aalst
country: Belgium
city: Antwerpen
country: Belgium
city: Brasschaat
country: Belgium
city: Brussel
country: Belgium
city: Roeselare
country: Belgium
city: Sint-Niklaas
country: Belgium
city: Wilrijk
country: Belgium
city: Caen Cedex 1
country: France
city: Le Mans Cedex 2
country: France
city: Lyon Cedex 08
country: France
city: Villejuif
country: France
city: Berlin
country: Germany
city: Cologne
country: Germany
city: Kassel
country: Germany
city: Barcelona N/A
country: Spain
city: Barcelona
country: Spain
city: Madrid N/A
country: Spain
city: Madrid
country: Spain
city: Málaga
country: Spain
city: London
country: United Kingdom
city: Sutton
country: United Kingdom
Study officials:
affiliation: Centocor, Inc.
name: Centocor, Inc. Clinical Trial
role: STUDY_DIRECTOR
References: