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

NCT00385827 | Terminated Phase 2 Results DMC

• 3 other identifiers: CR012346C0328T072006-001671-38
• Study Type: interventional
• Target: 106
• Locations: 7 countries
• Sites: 34

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).

Conditions

Cancer, Prostate

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  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.

  Baseline up to 12 weeks after last dose administration

• Part 2: Progression Free Survival (PFS)

  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.

  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 (4)

• Time to Clinical Deterioration (TtCD)

  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

• Number of Participants With Palliative Response

  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

• Number of Participants With Prostate Specific Antigen (PSA) Response

  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

• Overall Survival (OS)

  Start of treatment (Part 1)/Randomization (Part 2) until death, up to 2 years

Study Arms (3)

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

EXPERIMENTAL

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; Drug: Siltuximab; Drug: Prednisone

Mitoxantrone+Prednisone+Siltuximab (Part 2)

EXPERIMENTAL

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; Drug: Siltuximab; Drug: Prednisone

Mitoxantrone+Prednisone (Part 2)

ACTIVE COMPARATOR

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; Drug: Prednisone

Interventions

Mitoxantrone 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)

Mitoxantrone+Prednisone (Part 2); Mitoxantrone+Prednisone+Siltuximab (CNTO 328) (Part 1); Mitoxantrone+Prednisone+Siltuximab (Part 2)

Siltuximab 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

Also known as: CNTO 328

Mitoxantrone+Prednisone+Siltuximab (CNTO 328) (Part 1); Mitoxantrone+Prednisone+Siltuximab (Part 2)

Prednisone DRUG

Prednisone 5 mg orally twice daily

Mitoxantrone+Prednisone (Part 2); Mitoxantrone+Prednisone+Siltuximab (CNTO 328) (Part 1); Mitoxantrone+Prednisone+Siltuximab (Part 2)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centocor, Inc.: lead

Study Sites (34)

Unknown Facility

Norwalk, Connecticut, United States

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Port Saint Lucie, Florida, United States

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Atlanta, Georgia, United States

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Shreveport, Louisiana, United States

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Baltimore, Maryland, United States

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St Louis, Missouri, United States

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New York, New York, United States

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Philadelphia, Pennsylvania, United States

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Charleston, South Carolina, United States

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North Charleston, South Carolina, United States

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Milwaukee, Wisconsin, United States

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Innsbruck, Austria

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Sankt Veit an der Glan, Austria

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Vienna, Austria

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Wels, Austria

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Aalst, Belgium

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Antwerp, Belgium

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Brasschaat, Belgium

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Brussels, Belgium

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Roeselare, Belgium

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Sint-Niklaas, Belgium

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Wilrijk, Belgium

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Caen, France

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Le Mans, France

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Lyon, France

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Villejuif, France

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Berlin, Germany

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Cologne, Germany

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Kassel, Germany

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Barcelona, Spain

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Madrid, Spain

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Málaga, Spain

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London, United Kingdom

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Sutton, United Kingdom

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MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasms

Interventions

Mitoxantrone; siltuximab; Prednisone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Limitations and Caveats

Results of few secondary endpoints were not reported as the study was terminated early due to the premature suspension and subsequent halting of study enrollment.

Results Point of Contact

• Title: Director
• Organization: Janssen Research & Development

ClinicalTrialDisclosure@its.jnj.com

Study Officials

• Centocor, Inc. Clinical Trial

  Centocor, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2006
• First Posted: October 11, 2006
• Study Start: November 1, 2006
• Primary Completion: November 1, 2008
• Study Completion: November 1, 2008
• Last Updated: August 20, 2014
• Results First Posted: June 12, 2014

Record last verified: 2014-08

Locations

US (11); DE (3); ES (3); AU (4); BE (7); FR (4); GB (2)