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).
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
106
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 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 5 mg orally twice daily
Unnamed facility
Norwalk, Connecticut, United States
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.
Time frame: 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.
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
Time to Clinical Deterioration (TtCD)
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.
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
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Unnamed facility
Port Saint Lucie, Florida, United States
Unnamed facility
Atlanta, Georgia, United States
Unnamed facility
Shreveport, Louisiana, United States
Unnamed facility
Baltimore, Maryland, United States
Unnamed facility
St Louis, Missouri, United States
Unnamed facility
New York, New York, United States
Unnamed facility
Philadelphia, Pennsylvania, United States
Unnamed facility
Charleston, South Carolina, United States
Unnamed facility
North Charleston, South Carolina, United States
...and 24 more locations
Number of Participants With Palliative Response
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.
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
Number of Participants With Prostate Specific Antigen (PSA) Response
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.
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
Overall Survival (OS)
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.
Time frame: Start of treatment (Part 1)/Randomization (Part 2) until death, up to 2 years