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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Centocor Research & Development, Inc.
ClinicalTrials.gov Identifier:
NCT00992186
First received: September 29, 2009
Last updated: June 18, 2013
Last verified: June 2013
  Purpose

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).


Condition Intervention Phase
Prostate Cancer
Drug: Carlumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Centocor Research & Development, Inc.:

Primary Outcome Measures:
  • Percentage of Participants With Composite Response [ Time Frame: Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab ] [ Designated as safety issue: No ]
    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) [ Time Frame: Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab ] [ Designated as safety issue: No ]
    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) [ Time Frame: Week 8, 12, every 12 weeks up to 1 year after last dose of carlumab ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 2 weeks before first dose, every 4 weeks after first dose, Week 4 after last dose of carlumab ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
  • Maximum Observed Serum Concentration (Cmax) [ 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 ] [ Designated as safety issue: No ]
    The maximum observed analyte concentration was measured.

  • 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 ] [ Designated as safety issue: No ]
  • Half-life (t1/2) [ 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 ] [ Designated as safety issue: No ]
    The time measured for the serum concentration to decrease by one half.


Other Outcome Measures:
  • Time to Worsening in Eastern Cooperative Oncology Group (ECOG) Status Score [ Time Frame: Up to 2 weeks before first dose, pre-infusion, Week 4 after last dose of carlumab ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 46
Study Start Date: September 2009
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Carlumab Drug: Carlumab
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00992186

Locations
United States, Florida
Orange City, Florida, United States
United States, Michigan
Ann Arbor, Michigan, United States
United States, South Carolina
Charleston, South Carolina, United States
Belgium
Antwerpen, Belgium
Bruxelles, Belgium
Wilrijk, Belgium
Russian Federation
Moscow, Russian Federation
St Petersburg, Russian Federation
St-Petersburg, Russian Federation
United Kingdom
Birmingham, United Kingdom
Guildford, United Kingdom
Leeds, United Kingdom
Southampton, United Kingdom
Sutton, United Kingdom
Sponsors and Collaborators
Centocor Research & Development, Inc.
Investigators
Study Director: Centocor Research & Development, Inc., PA, USA Clinical Trial Centocor Research & Development, Inc.
  More Information

No publications provided

Responsible Party: Centocor Research & Development, Inc.
ClinicalTrials.gov Identifier: NCT00992186     History of Changes
Other Study ID Numbers: CR015907, 2009-011251-48, CNTO888PCR2001
Study First Received: September 29, 2009
Results First Received: March 29, 2013
Last Updated: June 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Centocor Research & Development, Inc.:
Prostate cancer
Infusion
Carlumab
CNTO 888

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms

ClinicalTrials.gov processed this record on October 30, 2014