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

Centocor Ortho Biotech

Status and phase

Completed

Phase 2

Phase 1

Conditions

Lung Neoplasms

Ovarian Neoplasms

Head and Neck Neoplasms

Colorectal Neoplasms

Pancreatic Neoplasms

Treatments

Drug: CNTO 328; Anti-interleukin-6 monoclonal antibody

Study type

Interventional

Funder types

Industry

Identifiers

NCT00841191

CR015580

2008-005180-33

CNTO328STM2001

Details and patient eligibility

About

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.

Full 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.

Enrollment

84 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

84 participants in 7 patient groups

Siltuximab 2.8 mg/kg (Cohort 1)

Experimental group

Treatment:

Drug: CNTO 328; Anti-interleukin-6 monoclonal antibody

Siltuximab 5.5 mg/kg (Cohort 2)

Experimental group

Treatment:

Drug: CNTO 328; Anti-interleukin-6 monoclonal antibody

Siltuximab 11 mg/kg (Cohort 3)

Experimental group

Treatment:

Drug: CNTO 328; Anti-interleukin-6 monoclonal antibody

Siltuximab 15 mg/kg (Cohort 4)

Experimental group

Treatment:

Drug: CNTO 328; Anti-interleukin-6 monoclonal antibody

Siltuximab 15 mg/kg (Expansion Cohort 5)

Experimental group

Treatment:

Drug: CNTO 328; Anti-interleukin-6 monoclonal antibody

Siltuximab 15 mg/kg (Ovarian Cancer Cohort 6)

Experimental group

Treatment:

Drug: CNTO 328; Anti-interleukin-6 monoclonal antibody

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

Experimental group

Treatment:

Drug: CNTO 328; Anti-interleukin-6 monoclonal antibody

Trial contacts and locations

Data sourced from clinicaltrials.gov

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