A Safety and Efficacy Study of Siltuximab (CNTO 328) in Male Subjects With Metastatic Hormone-Refractory Prostate Cancer (HRPC)

NCT ID: NCT00385827

Last Updated: 2014-08-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 106 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-11-30
• Study Completion Date: 2008-11-30

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.

Conditions

Cancer, Prostate

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Mitoxantrone+Prednisone+Siltuximab (CNTO 328) (Part 1)

In Part 1, mitoxantrone 12 milligram per square meter (mg/m\^2) will be given intravenously as a 30-minute infusion on Day 1 of each 3-week cycle until disease progression or unacceptable toxicity or up to 10 cycles (a maximum cumulative dose of approximately 120 mg/m\^2) along with siltuximab 6 mg/kilogram (mg/kg) intravenously as a 2 hour-infusion every 2 weeks until disease progression or unacceptable toxicity or up to a maximum of 1 year; and prednisone 5 mg orally twice daily starting with the first administration of mitoxantrone.

Group Type: EXPERIMENTAL

Mitoxantrone

Intervention Type: DRUG

Mitoxantrone 12 mg/m\^2 intravenously as a 30 minute infusion on Day 1 of each 3-week cycle until disease progression or unacceptable toxicity or up to 10 cycles (a maximum cumulative dose of approximately 120 mg/m\^2)

Siltuximab

Intervention Type: DRUG

Siltuximab 6 mg/kg intravenously as a 2 hour infusion every 2 weeks until disease progression or unacceptable toxicity or up to a maximum of 1 year

Prednisone

Intervention Type: DRUG

Prednisone 5 mg orally twice daily

Mitoxantrone+Prednisone+Siltuximab (Part 2)

In Part 2, mitoxantrone 12 mg/m\^2 will be given intravenously as a 30-minute infusion on Day 1 of each 3-week cycle until disease progression or unacceptable toxicity or up to 10 cycles (a maximum cumulative dose of approximately 120 mg/m\^2) along with siltuximab 6 mg/kg intravenously as a 2-hour infusion every 2 weeks until disease progression or unacceptable toxicity or up to a maximum of 1 year; and prednisone 5 mg orally twice daily starting with the first administration of mitoxantrone.

Group Type: EXPERIMENTAL

Mitoxantrone

Intervention Type: DRUG

Mitoxantrone 12 mg/m\^2 intravenously as a 30 minute infusion on Day 1 of each 3-week cycle until disease progression or unacceptable toxicity or up to 10 cycles (a maximum cumulative dose of approximately 120 mg/m\^2)

Siltuximab

Intervention Type: DRUG

Siltuximab 6 mg/kg intravenously as a 2 hour infusion every 2 weeks until disease progression or unacceptable toxicity or up to a maximum of 1 year

Prednisone

Intervention Type: DRUG

Prednisone 5 mg orally twice daily

Mitoxantrone+Prednisone (Part 2)

In Part 2, mitoxantrone 12 mg/m\^2 will be given intravenously as a 30-minute infusion on Day 1 of each 3-week cycle until disease progression or unacceptable toxicity or up to 10 cycles (a maximum cumulative dose of approximately 120 mg/m\^2) along with prednisone 5 mg orally twice daily starting with the first administration of mitoxantrone.

Group Type: ACTIVE_COMPARATOR

Mitoxantrone

Intervention Type: DRUG

Mitoxantrone 12 mg/m\^2 intravenously as a 30 minute infusion on Day 1 of each 3-week cycle until disease progression or unacceptable toxicity or up to 10 cycles (a maximum cumulative dose of approximately 120 mg/m\^2)

Prednisone

Intervention Type: DRUG

Prednisone 5 mg orally twice daily

Interventions

Mitoxantrone

Mitoxantrone 12 mg/m\^2 intravenously as a 30 minute infusion on Day 1 of each 3-week cycle until disease progression or unacceptable toxicity or up to 10 cycles (a maximum cumulative dose of approximately 120 mg/m\^2)

Intervention Type: DRUG

Siltuximab

Siltuximab 6 mg/kg intravenously as a 2 hour infusion every 2 weeks until disease progression or unacceptable toxicity or up to a maximum of 1 year

Intervention Type: DRUG

Prednisone

Prednisone 5 mg orally twice daily

Intervention Type: DRUG

Other Intervention Names

CNTO 328

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Centocor, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Centocor, Inc. Clinical Trial

Role: STUDY_DIRECTOR

Centocor, Inc.

Locations

Norwalk, Connecticut, United States

Port Saint Lucie, Florida, United States

Atlanta, Georgia, United States

Shreveport, Louisiana, United States

Baltimore, Maryland, United States

St Louis, Missouri, United States

New York, New York, United States

Philadelphia, Pennsylvania, United States

Charleston, South Carolina, United States

North Charleston, South Carolina, United States

Milwaukee, Wisconsin, United States

Innsbruck, , Austria

Sankt Veit an der Glan, , Austria

Vienna, , Austria

Wels, , Austria

Aalst, , Belgium

Antwerp, , Belgium

Brasschaat, , Belgium

Brussels, , Belgium

Roeselare, , Belgium

Sint-Niklaas, , Belgium

Wilrijk, , Belgium

Caen, , France

Le Mans, , France

Lyon, , France

Villejuif, , France

Berlin, , Germany

Cologne, , Germany

Kassel, , Germany

Barcelona, , Spain

Madrid, , Spain

Málaga, , Spain

London, , United Kingdom

Sutton, , United Kingdom

Countries

United States; Austria; Belgium; France; Germany; Spain; United Kingdom

Other Identifiers

C0328T07

Identifier Type: -

Identifier Source: secondary_id

2006-001671-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR012346

Identifier Type: -

Identifier Source: org_study_id