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

• ClinicalTrials.gov Identifier: NCT00385827
• Recruitment Status: Terminated
• First Posted: October 11, 2006
• Results First Posted: June 12, 2014
• Last Update Posted: August 20, 2014
• Sponsor: Centocor, Inc.
• Information provided by (Responsible Party): Centocor, Inc.

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Cancer, Prostate	Drug: Mitoxantrone; Drug: Siltuximab; Drug: Prednisone	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 106 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: November 2006
• Actual Primary Completion Date: November 2008
• Actual Study Completion Date: November 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Drug: 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); 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; Other Name: CNTO 328; Drug: Prednisone; Prednisone 5 mg orally twice daily
Experimental: 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.	Drug: 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); 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; Other Name: CNTO 328; Drug: Prednisone; Prednisone 5 mg orally twice daily
Active Comparator: 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.	Drug: 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); Drug: Prednisone; Prednisone 5 mg orally twice daily

Outcome Measures

Primary Outcome Measures :

1. Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 12 weeks after last dose administration ]
   An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
2. Part 2: Progression Free Survival (PFS) [ Time Frame: 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 ]
   The PFS is the time from the date of randomization until the first documented sign of progression (at least a 20 percent increase in the sum of the longest diameter [LD] of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new target or non-target lesions as per Response Evaluation Criteria in Solid Tumors [RECIST] or 3 or more new skeletal lesions on bone scan with confirmation of second bone scan or with clinical deterioration) or death, whichever occurs first.

Secondary Outcome Measures :

1. Time to Clinical Deterioration (TtCD) [ Time Frame: 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 ]
   The TtCD is defined as the time from the start of treatment (for participants in Part 1) or randomization (for participants in Part 2) until the first documented clinical deterioration (consists of pain requiring palliative (intended to relieve pain) intervention (a treatment given during the course of a research study), or death due to any cause, whichever occurs earlier.
2. Number of Participants With Palliative Response [ Time Frame: 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 ]
   Palliative response was defined as a 2-point or greater reduction from baseline pain, without a categorical increase in prescribed disease-related analgesic (drug used to control pain) use or at least a categorical decrease in disease-related analgesic use without a concomitant (given at the same time) increase in pain. Each component required confirmation at least 3 weeks later.
3. Number of Participants With Prostate Specific Antigen (PSA) Response [ Time Frame: 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 ]
   The PSA response is defined as at least a 50% reduction in PSA from the Baseline value, confirmed by a second PSA value at least 3 weeks after initial documentation of PSA response.
4. Overall Survival (OS) [ Time Frame: Start of treatment (Part 1)/Randomization (Part 2) until death, up to 2 years ]
   The OS is defined as the time from the date of start of treatment (for participants in Part 1) or randomization (for participants in Part 2) to death due to any cause. For participants who were alive at the time of analysis, OS was censored at the last contact date.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Connecticut

Norwalk, Connecticut, United States

United States, Florida

Port Saint Lucie, Florida, United States

United States, Georgia

Atlanta, Georgia, United States

United States, Louisiana

Shreveport, Louisiana, United States

United States, Maryland

Baltimore, Maryland, United States

United States, Missouri

Saint Louis, Missouri, United States

United States, New York

New York, New York, United States

United States, Pennsylvania

Philadelphia, Pennsylvania, United States

United States, South Carolina

Charleston, South Carolina, United States

N Charleston, South Carolina, United States

United States, Wisconsin

Milwaukee, Wisconsin, United States

Austria

Innsbruck, Austria

St Veit An Der Glan, Austria

Wels N/A, Austria

Wien, Austria

Belgium

Aalst, Belgium

Antwerpen, Belgium

Brasschaat, Belgium

Brussel, Belgium

Roeselare, Belgium

Sint-Niklaas, Belgium

Wilrijk, Belgium

France

Caen Cedex 1, France

Le Mans Cedex 2, France

Lyon Cedex 08, France

Villejuif, France

Germany

Berlin, Germany

Cologne, Germany

Kassel, Germany

Spain

Barcelona N/A, Spain

Barcelona, Spain

Madrid N/A, Spain

Madrid, Spain

Málaga, Spain

United Kingdom

London, United Kingdom

Sutton, United Kingdom

Sponsors and Collaborators

Centocor, Inc.

Investigators

• Study Director: Centocor, Inc. Clinical Trial; Centocor, Inc.

More Information

• Responsible Party: Centocor, Inc.
• ClinicalTrials.gov Identifier: NCT00385827
• Other Study ID Numbers: CR012346; C0328T07; 2006-001671-38 ( EudraCT Number )
• First Posted: October 11, 2006
• Results First Posted: June 12, 2014
• Last Update Posted: August 20, 2014
• Last Verified: August 2014

Keywords provided by Centocor, Inc.:

Cancer; Prostate; IL-6; Mitoxantrone; Metastatic prostate cancer

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases; Prednisone; Mitoxantrone; Siltuximab; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action