A Safety, Efficacy and Pharmacokinetic Study of Siltuximab (CNTO 328) in Participants With Solid Tumors

NCT ID: NCT00841191

Last Updated: 2014-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-31
• Study Completion Date: 2011-04-30

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.

Detailed Description

This is a 2-part, Phase 1/2, open-label (all people know the identity of the intervention), multiple-dose and dose-escalation study of intravenous (directly into a vein) siltuximab in participants with malignant solid tumors. The study tests the safety and effectiveness of the experimental drug, siltuximab, in participants with advanced cancer (abnormal tissue that grows and spreads in the body). This study also tests how siltuximab is cleared from the body and how the body reacts to it. For this reason blood tests will be performed and some characteristics of the tumor will be analyzed. Siltuximab will be given by intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) over 1 hour. In Phase 1 (Cohort 1-4) doses will be administered in a range of 2.8-15 milligram per kilogram (mg/kg). Cohort 5 of Phase 1 will receive the recommended dose and schedule as determined from Cohort 1-4. Participants in Phase 1 (Cohort 1-4) will receive 4 administrations of siltuximab over a 10-13 week period, while participants in Cohort 5 and Phase 2 will receive 12 administrations over a 33 week period. Follow-up visits up to 12 weeks after last dose will be scheduled. Participants may then be contacted for up to 1 year after the last dose for follow-up survival and disease status information. Efficacy will primarily be evaluated as per response evaluation criteria in solid tumors (RECIST) criteria. Participants' safety will be monitored at every visit.

Conditions

Ovarian Neoplasms; Pancreatic Neoplasms; Colorectal Neoplasms; Head and Neck Neoplasms; Lung Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Siltuximab 2.8 mg/kg (Cohort 1)

Group Type: EXPERIMENTAL

CNTO 328; Anti-interleukin-6 monoclonal antibody

Intervention Type: DRUG

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

Siltuximab 5.5 mg/kg (Cohort 2)

Group Type: EXPERIMENTAL

CNTO 328; Anti-interleukin-6 monoclonal antibody

Intervention Type: DRUG

Siltuximab 5.5 mg/kg will be administered as 1-hour intravenous infusion on Day 1, Day 28, Day 42 and Day 56

Siltuximab 11 mg/kg (Cohort 3)

Group Type: EXPERIMENTAL

CNTO 328; Anti-interleukin-6 monoclonal antibody

Intervention Type: DRUG

Siltuximab 11 mg/kg will be administered as 1-hour intravenous infusion on Day 1, Day 28, Day 49 and Day 70

Siltuximab 15 mg/kg (Cohort 4)

Group Type: EXPERIMENTAL

CNTO 328; Anti-interleukin-6 monoclonal antibody

Intervention Type: DRUG

Siltuximab 15 mg/kg will be administered as 1-hour intravenous infusion on Day 1, Day 28, Day 49 and Day 70

Siltuximab 15 mg/kg (Expansion Cohort 5)

Group Type: EXPERIMENTAL

CNTO 328; Anti-interleukin-6 monoclonal antibody

Intervention Type: DRUG

Siltuximab 15 mg/kg will be administered as 1-hour intravenous infusion once every 21 days for up to a total of 231 days

Siltuximab 15 mg/kg (Ovarian Cancer Cohort 6)

Group Type: EXPERIMENTAL

CNTO 328; Anti-interleukin-6 monoclonal antibody

Intervention Type: DRUG

Siltuximab 15 mg/kg will be administered as 1-hour intravenous infusion once every 21 days for up to a total of 231 days to participants with ovarian cancer.

Siltuximab 15 mg/kg (KRAS Mutant Tumors Cohort 7)

Group Type: EXPERIMENTAL

CNTO 328; Anti-interleukin-6 monoclonal antibody

Intervention Type: DRUG

Siltuximab 15 mg/kg will be administered as 1-hour intravenous infusion once every 21 days for up to a total of 231 days to participants with tumors harboring Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations or pancreatic cancer, or non-small cell lung cancer (NSCLC), colorectal cancer (CRC), or head and neck (H\&N) cancer that were refractory or resistant to anti-epidermal growth factor receptor (EGFR) therapy

Interventions

CNTO 328; Anti-interleukin-6 monoclonal antibody

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

Intervention Type: DRUG

CNTO 328; Anti-interleukin-6 monoclonal antibody

Siltuximab 5.5 mg/kg will be administered as 1-hour intravenous infusion on Day 1, Day 28, Day 42 and Day 56

Intervention Type: DRUG

CNTO 328; Anti-interleukin-6 monoclonal antibody

Siltuximab 11 mg/kg will be administered as 1-hour intravenous infusion on Day 1, Day 28, Day 49 and Day 70

Intervention Type: DRUG

CNTO 328; Anti-interleukin-6 monoclonal antibody

Siltuximab 15 mg/kg will be administered as 1-hour intravenous infusion on Day 1, Day 28, Day 49 and Day 70

Intervention Type: DRUG

CNTO 328; Anti-interleukin-6 monoclonal antibody

Siltuximab 15 mg/kg will be administered as 1-hour intravenous infusion once every 21 days for up to a total of 231 days

Intervention Type: DRUG

CNTO 328; Anti-interleukin-6 monoclonal antibody

Siltuximab 15 mg/kg will be administered as 1-hour intravenous infusion once every 21 days for up to a total of 231 days to participants with ovarian cancer.

Intervention Type: DRUG

CNTO 328; Anti-interleukin-6 monoclonal antibody

Siltuximab 15 mg/kg will be administered as 1-hour intravenous infusion once every 21 days for up to a total of 231 days to participants with tumors harboring Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations or pancreatic cancer, or non-small cell lung cancer (NSCLC), colorectal cancer (CRC), or head and neck (H\&N) cancer that were refractory or resistant to anti-epidermal growth factor receptor (EGFR) therapy

Intervention Type: DRUG

Other Intervention Names

Siltuximab; Siltoximab; Siltuximab; Siltuximab; Siltuximab; Siltuximab; Siltuximab

Eligibility Criteria

Inclusion Criteria

• 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)

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centocor, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Centocor, Inc. Clinical Trial

Role: STUDY_DIRECTOR

Centocor, Inc.

Locations

Philadelphia, Pennsylvania, United States

Houston, Texas, United States

Brussels, , Belgium

Wilrijk, , Belgium

Caen, , France

Lyon, , France

Villejuif, , France

Barcelona, , Spain

Madrid, , Spain

Birmingham, , United Kingdom

Edinburgh, , United Kingdom

Southampton, , United Kingdom

Countries

United States; Belgium; France; Spain; United Kingdom

Related Links

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_6051&studyid=191&filename=CR015580_CSR.pdf

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

Other Identifiers

CNTO328STM2001

Identifier Type: -

Identifier Source: secondary_id

2008-005180-33

Identifier Type: -

Identifier Source: secondary_id

CR015580

Identifier Type: -

Identifier Source: org_study_id