Back to resultsA Study of the Safety and Efficacy of Single-agent Carlumab (an Anti-Chemokine Ligand 2 [CCL2]) in Participants With Metastatic Castrate-Resistant Prostate Cancer
Primary Purpose
Prostate Cancer
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Carlumab
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer focused on measuring Prostate cancer, Infusion, Carlumab, CNTO 888
Eligibility Criteria
Inclusion Criteria:
- Histological documentation of adenocarcinoma of the prostate
- Received at least 1 but no more than 2 prior docetaxel-based chemotherapy regimens and had disease progression following the last therapy
- Serum prostate specific antigen (PSA) greater than or equal to 5.0 nanogram/milliliter (ng/ml) within 4 weeks prior to the first dose of study agent
- Orchiectomy (surgery to remove one or both testicles) or testosterone less than 50 nanogram/deciliter by means of pharmacological/chemical castration within 4 weeks prior to the first dose of study agent
- At least 6 weeks from prior docetaxel chemotherapy regimen to first dose of study agent
Exclusion Criteria:
- Experience a hormonal treatment withdrawal response (including a lowering of PSA that was previously rising or symptomatic improvement)
- Known or symptomatic Central Nervous System metastases
- Residual toxicities resulting from previous therapy that are Grade 2 or more (except for alopecia)
- Known allergies, hypersensitivity, or intolerance to carlumab or its excipients or clinically significant reactions to chimeric or human proteins
- Vaccinated with live, attenuated vaccines within 4 weeks prior to the first dose of study agent
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Carlumab
Arm Description
Outcomes
Primary Outcome Measures
Percentage of Participants With Composite Response
The composite response is measured by change from Baseline in skeletal lesions, extra-skeletal lesions, and prostate specific antigen (PSA) values. A participant is considered to have composite response, if 1 of the following responses occurs after the first dose of carlumab: (1) Complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST), (2) PSA response at 12 weeks and absence of skeletal and extra-skeletal progression or (3) Stable disease at 24 weeks defined as the absence of PSA, skeletal, or extra-skeletal progression.
Secondary Outcome Measures
Percentage of Participants With Objective Tumor Response
Objective response based on assessment of confirmed CR or PR according to RECIST. CR defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30 percent (%) decrease in sum of the diameters of the target lesions taking as reference the Baseline sum diameters. Confirmed responses are those that persist on repeat imaging study for at least 4 weeks after initial documentation of response.
Progression-Free Survival (PFS)
The PFS is defined as the time from the date of initiation of study treatment to the date of initial documented skeletal or extra-skeletal progressive disease, or date of death, whichever occurs first. A participant is considered to have extra-skeletal disease progression if the disease has progressed as per the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria. A participant is considered to have skeletal disease progression if they have 1 post-baseline bone scan demonstrating 2 or more new skeletal lesions compared to Baseline and confirmed by a second bone scan 6 to 12 weeks later or with evidence of clinical progression.
Overall Survival (OS)
The OS is defined as the time from the date of initiation of study treatment to death due to any cause. Participants were followed for 1 year after the last administration of carlumab for survival or until the end of study, whichever occurs first. For participants with unknown survival status as of the data cutoff date, OS was censored at the last date that the participant was known to be alive.
Percentage of Participants With Prostate Specific Antigen (PSA) Response
The PSA response for participants with elevated PSA levels at Baseline (more than or equal to 5 nanogram per milliliter (ng/mL) is defined as at least a 50% reduction in PSA from the Baseline value, confirmed by a second PSA value measurement 3 or more weeks later.
Percentage of Participants With Urinary Crosslinked N-Telopeptide of Type I Collagen (NTx) Response
Urinary NTx response for participants with elevated NTx level at Baseline (more than or equal to 50 nanomole per millimole (nmol/mmol)) is defined as a 30% reduction from Baseline NTx value, confirmed by a second NTx value 3 or more weeks later.
Percentage of Participants With Pain Response
Pain response is defined as 2-point decrease from Baseline in 'worst pain' intensity score (item 3) on the Brief Pain Inventory (BPI) questionnaire. The BPI is a nine-item questionnaire with 0 to 10 numeric rating scales in response to each item, where 0=No pain and 10=Pain as bad as you can imagine. Measure can be scored by item, with lower scores being indicative of less pain or pain interference.
Time to Radiologic Response
Radiologic response based on assessment of confirmed CR or PR according to RECIST. CR defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30% decrease in sum of the diameters of the target lesions taking as reference the Baseline sum diameters. Confirmed responses are those that persist on repeat imaging study for at least 4 weeks after initial documentation of response.
Duration of Radiologic Response
Radiologic response based on assessment of confirmed CR or PR according to RECIST. CR defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30% decrease in sum of the diameters of the target lesions taking as reference the Baseline sum diameters. Confirmed responses are those that persist on repeat imaging study for at least 4 weeks after initial documentation of response.
Minimum Observed Serum Concentration (Cmin)
Maximum Observed Serum Concentration (Cmax)
The maximum observed analyte concentration was measured.
Area Under the Serum Concentration Versus Time Curve Between 0 And 14 Days (AUC 0-14d)
Half-life (t1/2)
The time measured for the serum concentration to decrease by one half.
Full Information
NCT ID
NCT00992186
First Posted
September 29, 2009
Last Updated
June 18, 2013
Sponsor
Centocor Research & Development, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT00992186
Brief Title
A Study of the Safety and Efficacy of Single-agent Carlumab (an Anti-Chemokine Ligand 2 [CCL2]) in Participants With Metastatic Castrate-Resistant Prostate Cancer
Official Title
An Open-Label, Multicenter, Phase 2 Study of Single-Agent CNTO 888 (an Anti-CCL2 Monoclonal Antibody) for the Treatment of Subjects With Metastatic Castrate-Resistant Prostate Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
June 2013
Overall Recruitment Status
Completed
Study Start Date
September 2009 (undefined)
Primary Completion Date
July 2011 (Actual)
Study Completion Date
July 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centocor Research & Development, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to determine the safety and effectiveness of the study drug carlumab in participants with metastatic castrate-resistant prostate cancer (cancer of the gland that makes fluid that aids movement of sperm).
Detailed Description
This is an open-label (all people know the identity of the intervention), multicenter trial (conducted in more than one center) in participants with metastatic castrate-resistant prostate cancer. The trial consists of 3 phases: screening period, treatment period of approximately 4 months, and a follow-up period (Week 1, 4, 8 and 12 after the last dose) of up to 12 weeks after the administration of last dose. The participants will receive carlumab at the dose of 15 milligram/kilogram (mg/kg) by intravenous (into a vein) infusion (a fluid or a medicine delivered into a vein by way of a needle) at a constant rate over a 90 minute period once every 2 weeks until disease progression. Efficacy of the participants will be primarily evaluated by composite response. Participants' safety will be monitored throughout the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
Prostate cancer, Infusion, Carlumab, CNTO 888
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
46 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Carlumab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Carlumab
Intervention Description
Carlumab diluted in 5 percent (%) dextrose administered at the dose of 15 milligram per kilogram (mg/kg) by intravenous (into a vein) infusion (a fluid or a medicine delivered into a vein by way of a needle) at a constant rate over a 90 minute period once every 2 weeks until disease progression.
Primary Outcome Measure Information:
Title
Percentage of Participants With Composite Response
Description
The composite response is measured by change from Baseline in skeletal lesions, extra-skeletal lesions, and prostate specific antigen (PSA) values. A participant is considered to have composite response, if 1 of the following responses occurs after the first dose of carlumab: (1) Complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST), (2) PSA response at 12 weeks and absence of skeletal and extra-skeletal progression or (3) Stable disease at 24 weeks defined as the absence of PSA, skeletal, or extra-skeletal progression.
Time Frame
Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab
Secondary Outcome Measure Information:
Title
Percentage of Participants With Objective Tumor Response
Description
Objective response based on assessment of confirmed CR or PR according to RECIST. CR defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30 percent (%) decrease in sum of the diameters of the target lesions taking as reference the Baseline sum diameters. Confirmed responses are those that persist on repeat imaging study for at least 4 weeks after initial documentation of response.
Time Frame
Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab
Title
Progression-Free Survival (PFS)
Description
The PFS is defined as the time from the date of initiation of study treatment to the date of initial documented skeletal or extra-skeletal progressive disease, or date of death, whichever occurs first. A participant is considered to have extra-skeletal disease progression if the disease has progressed as per the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria. A participant is considered to have skeletal disease progression if they have 1 post-baseline bone scan demonstrating 2 or more new skeletal lesions compared to Baseline and confirmed by a second bone scan 6 to 12 weeks later or with evidence of clinical progression.
Time Frame
Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab
Title
Overall Survival (OS)
Description
The OS is defined as the time from the date of initiation of study treatment to death due to any cause. Participants were followed for 1 year after the last administration of carlumab for survival or until the end of study, whichever occurs first. For participants with unknown survival status as of the data cutoff date, OS was censored at the last date that the participant was known to be alive.
Time Frame
Week 8, 12, every 12 weeks up to 1 year after last dose of carlumab
Title
Percentage of Participants With Prostate Specific Antigen (PSA) Response
Description
The PSA response for participants with elevated PSA levels at Baseline (more than or equal to 5 nanogram per milliliter (ng/mL) is defined as at least a 50% reduction in PSA from the Baseline value, confirmed by a second PSA value measurement 3 or more weeks later.
Time Frame
Up to 2 weeks before first dose, every 4 weeks after first dose, Week 4, 8, 12 after the last dose of carlumab
Title
Percentage of Participants With Urinary Crosslinked N-Telopeptide of Type I Collagen (NTx) Response
Description
Urinary NTx response for participants with elevated NTx level at Baseline (more than or equal to 50 nanomole per millimole (nmol/mmol)) is defined as a 30% reduction from Baseline NTx value, confirmed by a second NTx value 3 or more weeks later.
Time Frame
Up to 2 weeks before first dose, every 4 weeks after first dose, Week 4, 8, 12 after the last dose of carlumab
Title
Percentage of Participants With Pain Response
Description
Pain response is defined as 2-point decrease from Baseline in 'worst pain' intensity score (item 3) on the Brief Pain Inventory (BPI) questionnaire. The BPI is a nine-item questionnaire with 0 to 10 numeric rating scales in response to each item, where 0=No pain and 10=Pain as bad as you can imagine. Measure can be scored by item, with lower scores being indicative of less pain or pain interference.
Time Frame
Up to 2 weeks before first dose, every 4 weeks after first dose, Week 4 after last dose of carlumab
Title
Time to Radiologic Response
Description
Radiologic response based on assessment of confirmed CR or PR according to RECIST. CR defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30% decrease in sum of the diameters of the target lesions taking as reference the Baseline sum diameters. Confirmed responses are those that persist on repeat imaging study for at least 4 weeks after initial documentation of response.
Time Frame
Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab
Title
Duration of Radiologic Response
Description
Radiologic response based on assessment of confirmed CR or PR according to RECIST. CR defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30% decrease in sum of the diameters of the target lesions taking as reference the Baseline sum diameters. Confirmed responses are those that persist on repeat imaging study for at least 4 weeks after initial documentation of response.
Time Frame
Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab
Title
Minimum Observed Serum Concentration (Cmin)
Time Frame
Pre-dose and at the end of infusion for each Dose; 2, 4 hour (hr) and 1 week after Dose 1; 2 hr after Dose 4; Week 1, 4, 8 and 12 post-last dose
Title
Maximum Observed Serum Concentration (Cmax)
Description
The maximum observed analyte concentration was measured.
Time Frame
Pre-dose and at the end of infusion for each Dose; 2, 4 hour (hr) and 1 week after Dose 1; 2 hr after Dose 4; Week 1, 4, 8 and 12 post-last dose
Title
Area Under the Serum Concentration Versus Time Curve Between 0 And 14 Days (AUC 0-14d)
Time Frame
Pre-dose, at the end of infusion, 2, 4 hr and 1 week after end of infusion for the first dose
Title
Half-life (t1/2)
Description
The time measured for the serum concentration to decrease by one half.
Time Frame
Pre-dose and at the end of infusion for each Dose; 2, 4 hour (hr) and 1 week after Dose 1; 2 hr after Dose 4; Week 1, 4, 8 and 12 post-last dose
Other Pre-specified Outcome Measures:
Title
Time to Worsening in Eastern Cooperative Oncology Group (ECOG) Status Score
Description
A worsening in ECOG performance status score was defined as greater than or equal to 1-point increase from Baseline. Time to worsening is defined as the number of days from first dose to the first day of worsening in ECOG score, or death, whichever occurred first. ECOG is a 5-point scale 0=Fully active, 1=Ambulatory, carry out work of sedentary nature, 2=Ambulatory, capable of all selfcare, 3=Capable of limited selfcare, confined to bed or chair more than 50% of waking hours, 4=Completely disabled, no selfcare, totally confined to bed or chair, 5=Dead.
Time Frame
Up to 2 weeks before first dose, pre-infusion, Week 4 after last dose of carlumab
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histological documentation of adenocarcinoma of the prostate
Received at least 1 but no more than 2 prior docetaxel-based chemotherapy regimens and had disease progression following the last therapy
Serum prostate specific antigen (PSA) greater than or equal to 5.0 nanogram/milliliter (ng/ml) within 4 weeks prior to the first dose of study agent
Orchiectomy (surgery to remove one or both testicles) or testosterone less than 50 nanogram/deciliter by means of pharmacological/chemical castration within 4 weeks prior to the first dose of study agent
At least 6 weeks from prior docetaxel chemotherapy regimen to first dose of study agent
Exclusion Criteria:
Experience a hormonal treatment withdrawal response (including a lowering of PSA that was previously rising or symptomatic improvement)
Known or symptomatic Central Nervous System metastases
Residual toxicities resulting from previous therapy that are Grade 2 or more (except for alopecia)
Known allergies, hypersensitivity, or intolerance to carlumab or its excipients or clinically significant reactions to chimeric or human proteins
Vaccinated with live, attenuated vaccines within 4 weeks prior to the first dose of study agent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Centocor Research & Development, Inc., PA, USA Clinical Trial
Organizational Affiliation
Centocor Research & Development, Inc.
Official's Role
Study Director
Facility Information:
City
Orange City
State/Province
Florida
Country
United States
City
Ann Arbor
State/Province
Michigan
Country
United States
City
Charleston
State/Province
South Carolina
Country
United States
City
Antwerpen
Country
Belgium
City
Bruxelles
Country
Belgium
City
Wilrijk
Country
Belgium
City
Moscow
Country
Russian Federation
City
St Petersburg
Country
Russian Federation
City
St-Petersburg
Country
Russian Federation
City
Birmingham
Country
United Kingdom
City
Guildford
Country
United Kingdom
City
Leeds
Country
United Kingdom
City
Southampton
Country
United Kingdom
City
Sutton
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
A Study of the Safety and Efficacy of Single-agent Carlumab (an Anti-Chemokine Ligand 2 [CCL2]) in Participants With Metastatic Castrate-Resistant Prostate Cancer
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