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
- Registration Number
- NCT00992186
- Lead Sponsor
- Centocor Research & Development, Inc.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 46
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Carlumab Carlumab -
- Primary Outcome Measures
Name Time Method Percentage of Participants With Composite Response Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab 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
Name Time Method Percentage of Participants With Objective Tumor Response Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab 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) Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab 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) Week 8, 12, every 12 weeks up to 1 year after last dose of carlumab 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 Up to 2 weeks before first dose, every 4 weeks after first dose, Week 4, 8, 12 after the last dose of carlumab 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 Up to 2 weeks before first dose, every 4 weeks after first dose, Week 4, 8, 12 after the last dose of carlumab 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 Up to 2 weeks before first dose, every 4 weeks after first dose, Week 4 after last dose of carlumab 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 Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab 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 Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab 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) 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) 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 The maximum observed analyte concentration was measured.
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) 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 The time measured for the serum concentration to decrease by one half.