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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Carlumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Carlumab<br> | Drug: Carlumab<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab | 
| 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. | Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab | 
| 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. | Week 8, 12, every 12 weeks up to 1 year after last dose of carlumab | 
| 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. | Up to 2 weeks before first dose, every 4 weeks after first dose, Week 4, 8, 12 after the last dose of carlumab | 
| 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. | Up to 2 weeks before first dose, every 4 weeks after first dose, Week 4, 8, 12 after the last dose of carlumab | 
| 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. | Up to 2 weeks before first dose, every 4 weeks after first dose, Week 4 after last dose of carlumab | 
| 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. | Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab | 
| 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. | Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab | 
| Minimum Observed Serum Concentration (Cmin) |  | 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 | 
| Maximum Observed Serum Concentration (Cmax) | The maximum observed analyte concentration was measured. | 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 | 
| Area Under the Serum Concentration Versus Time Curve Between 0 And 14 Days (AUC 0-14d) |  | Pre-dose, at the end of infusion, 2, 4 hr and 1 week after end of infusion for the first dose | 
| Half-life (t1/2) | The time measured for the serum concentration to decrease by one half. | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate cancer, Infusion, Carlumab, CNTO 888