Trial Outcomes & Findings for A Safety and Efficacy Study of Siltuximab (CNTO 328) in Male Subjects With Metastatic Hormone-Refractory Prostate Cancer (HRPC) (NCT NCT00385827)

Last Updated: 2014-08-20

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

106 participants

Primary outcome timeframe

Baseline up to 12 weeks after last dose administration

Results posted on

2014-08-20

Participant Flow

Participant milestones

Participant milestones
Measure	Part 1: Mitoxantrone + Prednisone + Siltuximab Participants received mitoxantrone 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 or up to 10 cycles (a maximum cumulative dose of approximately 120 mg/m\^2) along with siltuximab (CNTO 328) 6 milligram per 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 milligram (mg) orally twice daily starting with the first administration of mitoxantrone.	Part 2: Mitoxantrone + Prednisone Participants received mitoxantrone 12 mg/m\^2 intravenously as a 30-minute 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.	Part 2: Mitoxantrone + Prednisone + Siltuximab Participants received 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) 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.
Part 1 STARTED	9	0	0
Part 1 Treated	9	0	0
Part 1 COMPLETED	0	0	0
Part 1 NOT COMPLETED	9	0	0
Part 2 STARTED	0	49	48
Part 2 Treated	0	47	46
Part 2 COMPLETED	0	16	0
Part 2 NOT COMPLETED	0	33	48

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1: Mitoxantrone + Prednisone + Siltuximab Participants received mitoxantrone 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 or up to 10 cycles (a maximum cumulative dose of approximately 120 mg/m\^2) along with siltuximab (CNTO 328) 6 milligram per 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 milligram (mg) orally twice daily starting with the first administration of mitoxantrone.	Part 2: Mitoxantrone + Prednisone Participants received mitoxantrone 12 mg/m\^2 intravenously as a 30-minute 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.	Part 2: Mitoxantrone + Prednisone + Siltuximab Participants received 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) 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.
Part 1 Adverse Event	1	0	0
Part 1 Death	2	0	0
Part 1 Lack of Efficacy	5	0	0
Part 1 Other	1	0	0
Part 2 Adverse Event	0	6	10
Part 2 Death	0	0	2
Part 2 Lack of Efficacy	0	14	13
Part 2 Randomized but not treated	0	2	2
Part 2 Other	0	11	21

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1: Mitoxantrone + Prednisone + Siltuximab n=9 Participants Participants received mitoxantrone 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 or up to 10 cycles (a maximum cumulative dose of approximately 120 mg/m\^2) along with siltuximab (CNTO 328) 6 milligram per 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 milligram (mg) orally twice daily starting with the first administration of mitoxantrone.	Part 2: Mitoxantrone + Prednisone n=49 Participants Participants received mitoxantrone 12 mg/m\^2 intravenously as a 30-minute 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.	Part 2: Mitoxantrone + Prednisone + Siltuximab n=48 Participants Participants received 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) 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.	Total n=106 Participants Total of all reporting groups
Age, Continuous	69.4 years STANDARD_DEVIATION 7.89 • n=5 Participants	67.8 years STANDARD_DEVIATION 7.83 • n=7 Participants	67.9 years STANDARD_DEVIATION 9.28 • n=5 Participants	68 years STANDARD_DEVIATION 8.46 • n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	49 Participants n=7 Participants	48 Participants n=5 Participants	106 Participants n=4 Participants
Region of Enrollment AUSTRIA	0 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants	3 participants n=4 Participants
Region of Enrollment BELGIUM	0 participants n=5 Participants	6 participants n=7 Participants	6 participants n=5 Participants	12 participants n=4 Participants
Region of Enrollment FRANCE	0 participants n=5 Participants	15 participants n=7 Participants	12 participants n=5 Participants	27 participants n=4 Participants
Region of Enrollment GERMANY	0 participants n=5 Participants	4 participants n=7 Participants	5 participants n=5 Participants	9 participants n=4 Participants
Region of Enrollment SPAIN	0 participants n=5 Participants	7 participants n=7 Participants	4 participants n=5 Participants	11 participants n=4 Participants
Region of Enrollment UNITED KINGDOM	0 participants n=5 Participants	5 participants n=7 Participants	6 participants n=5 Participants	11 participants n=4 Participants
Region of Enrollment UNITED STATES	9 participants n=5 Participants	11 participants n=7 Participants	13 participants n=5 Participants	33 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline up to 12 weeks after last dose administration

Population: Safety population in Part 1 included all participants who received at least one dose of study drug.

Outcome measures

Outcome measures
Measure	Part 1: Mitoxantrone + Prednisone + Siltuximab n=9 Participants Participants received mitoxantrone 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 or up to 10 cycles (a maximum cumulative dose of approximately 120 mg/m\^2) along with siltuximab (CNTO 328) 6 milligram per 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 milligram (mg) orally twice daily starting with the first administration of mitoxantrone.	Part 2: Mitoxantrone + Prednisone + Siltuximab Participants received 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) 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.	Part 2: Mitoxantrone + Prednisone + Siltuximab Participants received 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) 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.
Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	9 participants	—	—
Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	5 participants	—	—

PRIMARY outcome

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

Population: Intent-to-treat (ITT) population in Part 2 included all randomized participants.

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.

Outcome measures

Outcome measures
Measure	Part 1: Mitoxantrone + Prednisone + Siltuximab n=49 Participants Participants received mitoxantrone 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 or up to 10 cycles (a maximum cumulative dose of approximately 120 mg/m\^2) along with siltuximab (CNTO 328) 6 milligram per 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 milligram (mg) orally twice daily starting with the first administration of mitoxantrone.	Part 2: Mitoxantrone + Prednisone + Siltuximab n=48 Participants Participants received 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) 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.	Part 2: Mitoxantrone + Prednisone + Siltuximab Participants received 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) 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.
Part 2: Progression Free Survival (PFS)	228.0 days Interval 155.0 to 303.0	97.0 days Interval 84.0 to 179.0	—

SECONDARY outcome

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

Population: Analysis population included all participants who received at least one dose of study drug in Part 1 and all randomized participants in Part 2.

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.

Outcome measures

Outcome measures
Measure	Part 1: Mitoxantrone + Prednisone + Siltuximab n=9 Participants Participants received mitoxantrone 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 or up to 10 cycles (a maximum cumulative dose of approximately 120 mg/m\^2) along with siltuximab (CNTO 328) 6 milligram per 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 milligram (mg) orally twice daily starting with the first administration of mitoxantrone.	Part 2: Mitoxantrone + Prednisone + Siltuximab n=49 Participants Participants received 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) 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.	Part 2: Mitoxantrone + Prednisone + Siltuximab n=48 Participants Participants received 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) 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.
Time to Clinical Deterioration (TtCD)	199.0 days Interval 107.0 to Upper limit of the confidence interval was not reachable as data was not matured at the time of the analysis, due to early study termination.	298.0 days Interval 128.0 to 342.0	183.0 days Interval 142.0 to 274.0

SECONDARY outcome

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

Population: Data for this outcome measure was not analyzed because minimal efficacy analysis (primary and key secondary endpoints) was done due to early termination of study.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

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

Population: Analysis population included all participants who received at least one dose of study drug in Part 1 and all randomized participants in Part 2. Here, 'N' (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Part 1: Mitoxantrone + Prednisone + Siltuximab n=9 Participants Participants received mitoxantrone 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 or up to 10 cycles (a maximum cumulative dose of approximately 120 mg/m\^2) along with siltuximab (CNTO 328) 6 milligram per 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 milligram (mg) orally twice daily starting with the first administration of mitoxantrone.	Part 2: Mitoxantrone + Prednisone + Siltuximab n=46 Participants Participants received 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) 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.	Part 2: Mitoxantrone + Prednisone + Siltuximab n=45 Participants Participants received 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) 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.
Number of Participants With Prostate Specific Antigen (PSA) Response	4 participants	12 participants	7 participants

SECONDARY outcome

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

Population: Analysis population included all participants who received at least one dose of study drug in Part 1 and all randomized participants in Part 2.

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.

Outcome measures

Outcome measures
Measure	Part 1: Mitoxantrone + Prednisone + Siltuximab n=9 Participants Participants received mitoxantrone 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 or up to 10 cycles (a maximum cumulative dose of approximately 120 mg/m\^2) along with siltuximab (CNTO 328) 6 milligram per 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 milligram (mg) orally twice daily starting with the first administration of mitoxantrone.	Part 2: Mitoxantrone + Prednisone + Siltuximab n=49 Participants Participants received 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) 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.	Part 2: Mitoxantrone + Prednisone + Siltuximab n=48 Participants Participants received 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) 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.
Overall Survival (OS)	368.0 days Interval 214.0 to Upper limit of the confidence interval was not reachable as data was not matured at the time of the analysis, due to early study termination.	394.0 days Interval 311.0 to 438.0	311.0 days Interval 226.0 to Upper limit of the confidence interval was not reachable as data was not matured at the time of the analysis, due to early study termination.

Adverse Events

Part 1: Mitoxantrone + Prednisone + Siltuximab

Serious events: 5 serious events

Other events: 9 other events

Deaths: 0 deaths

Part 2: Mitoxantrone + Prednisone

Serious events: 18 serious events

Other events: 42 other events

Deaths: 0 deaths

Part 2: Mitoxantrone + Prednisone + Siltuximab

Serious events: 18 serious events

Other events: 46 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Director

Janssen Research & Development

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60