A Safety, Efficacy and Pharmacokinetic Study of Siltuximab (CNTO 328) in Participants With Solid Tumors
A Phase 1/2, Multiple-Dose, Dose-Escalation Study to Assess the Safety, Efficacy, and Pharmacokinetics of Intravenous CNTO 328, an Anti-Interleukin 6 (IL-6) Monoclonal Antibody, in Subjects With Solid Tumors
3 other identifiers
interventional
84
5 countries
12
Brief Summary
The purpose of this study is to determine the recommended dose of siltuximab monotherapy, in participants with solid malignant (cancerous) tumors (a mass in a specific area) and to estimate the clinical benefit of siltuximab monotherapy in participants with ovarian cancer and with Kirsten rat sarcoma viral oncogene homolog (KRAS) mutant tumors.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2009
Typical duration for phase_1
12 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 9, 2009
CompletedFirst Posted
Study publicly available on registry
February 11, 2009
CompletedStudy Start
First participant enrolled
March 1, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2011
CompletedMay 14, 2014
May 1, 2014
2.1 years
February 9, 2009
May 13, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Participants With Clinical Benefit Response (CBR)
The CBR is a confirmed complete response (CR), partial response (PR), or stable disease (SD) lasting at least for 6 weeks as per response evaluation criteria in solid tumors (RECIST) criteria. CR: disappearance of all target and non-target lesions and normalization of tumor marker level; PR: at least 30 percent decrease in sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since treatment started.
Baseline until disease progression or withdrawal of consent, assessed every 9 weeks up to Week 4 after last dose administration
Secondary Outcomes (20)
Percentage of Participants With Overall Response
Baseline until disease progression or withdrawal of consent, assessed every 9 weeks up to Week 4 after last dose administration
Number of Participants With Tumor Marker Response
Baseline until disease progression or withdrawal of consent, assessed every 9 weeks up to Week 4 after last dose administration
Percentage of Participants With Hemoglobin (Hb) Response
Baseline up to Week 4 after last dose administration
Progression Free Survival (PFS)
Baseline until disease progression or death, assessed every 9 weeks up to Week 4 after last dose administration
Overall Survival (OS)
From first dose administration until death, assessed every 3 months up to 12 months after last dose administration
- +15 more secondary outcomes
Study Arms (7)
Siltuximab 2.8 mg/kg (Cohort 1)
EXPERIMENTALSiltuximab 5.5 mg/kg (Cohort 2)
EXPERIMENTALSiltuximab 11 mg/kg (Cohort 3)
EXPERIMENTALSiltuximab 15 mg/kg (Cohort 4)
EXPERIMENTALSiltuximab 15 mg/kg (Expansion Cohort 5)
EXPERIMENTALSiltuximab 15 mg/kg (Ovarian Cancer Cohort 6)
EXPERIMENTALSiltuximab 15 mg/kg (KRAS Mutant Tumors Cohort 7)
EXPERIMENTALInterventions
Siltuximab 2.8 milligram per kilogram (mg/kg) will be administered as 1-hour intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) on Day 1, Day 28, Day 42 and Day 56
Eligibility Criteria
You may qualify if:
- Histologic (pertaining to body tissues) or cytologic (pertaining to cells) documentation of malignancy (cancer or other progressively enlarging and spreading tumor) as follows: malignant solid tumors (Cohort 1-4 only); Cohorts 5 and Phase 2: epithelial (tissue covering outer layers of most body organs and parts) ovarian cancers (abnormal tissue growth) that have progressed on or after standard therapy, or for which there is no effective therapy or platinum resistant and taxane resistant, defined as progression on or within 6 months of completing therapy with taxane and platinum either alone or in combination (unless contraindications for taxane or platinum exist), and for which there is no effective therapy, or participants with known KRAS mutant tumors or pancreatic cancer, or non-small cell lung cancer (NSCLC), colorectal cancer (CRC) or head and neck (H\&N) cancer that are refractory or resistant to anti-epidermal growth factor receptor (EGFR) therapy and all participants must have received at least 1 line of standard chemotherapy
- Eastern cooperative oncology group (ECOG) performance status score less than or equal to 2
- Participants must have recovered from reversible toxicity (any harmful effect of a drug or poison) of previous treatment to less than or equal to grade 1 or an acceptable baseline
- Women of child bearing potential must have a negative pregnancy test at screening
- Cohort 5 and Phase 2 cohorts must have evaluable or measurable disease (defined by response evaluation criteria in solid tumors \[RECIST\], as applicable)
You may not qualify if:
- Received any prior systemic therapy or had major surgery for the cancer under study within 4 weeks (in the case of nitrosoureas and mitomycin C within 6 weeks) prior to first siltuximab administration
- Prior anti-interleukin 6 (IL-6) targeted therapy
- Serious concurrent illness or history of uncontrolled heart disease such as: unstable angina (chest pain due to decreased oxygen being supplied to the heart), congestive heart failure (failure of the heart resulting in fluid build-up in the lungs, other body tissues, or both), myocardial infarction (heart attack) within preceding 12 months, clinically significant rhythm or conduction abnormality
- Participants with known allergies (over sensitivity to a substance) or clinically significant reactions to murine, chimeric, or human proteins
- Any uncontrolled medical condition, including the presence of laboratory abnormalities, that places the participant at unacceptable risk by participating in the study or confounds the ability to interpret data from the study
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Centocor, Inc.lead
Study Sites (12)
Unknown Facility
Philadelphia, Pennsylvania, United States
Unknown Facility
Houston, Texas, United States
Unknown Facility
Brussels, Belgium
Unknown Facility
Wilrijk, Belgium
Unknown Facility
Caen, France
Unknown Facility
Lyon, France
Unknown Facility
Villejuif, France
Unknown Facility
Barcelona, Spain
Unknown Facility
Madrid, Spain
Unknown Facility
Birmingham, United Kingdom
Unknown Facility
Edinburgh, United Kingdom
Unknown Facility
Southampton, United Kingdom
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Centocor, Inc. Clinical Trial
Centocor, Inc.
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 9, 2009
First Posted
February 11, 2009
Study Start
March 1, 2009
Primary Completion
April 1, 2011
Study Completion
April 1, 2011
Last Updated
May 14, 2014
Record last verified: 2014-05