Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Lung Neoplasms

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Nevus

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

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Lung Diseases

Respiratory Tract Diseases

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Endocrine System Diseases

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Genital Diseases, Female

Genital Diseases

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Female Urogenital Diseases

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Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

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Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Immunoglobulins

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Siltuximab

Immunologic Factors

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

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

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

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 will be administered as 1-hour intravenous infusion on Day 1, Day 28, Day 49 and Day 70

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 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 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

Centocor, Inc. Clinical Trial

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.

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.

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

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.

Overall response is defined as a confirmed CR or PR using RECIST criteria. CR is defined as disappearance of all target lesions and non-target lesions and normalization of tumor marker level, and PR is defined as at least 30 percent decrease in sum of the LD of target lesions, taking as reference the baseline sum LD.

According to gynecologic cancer intergroup criteria (GCIC), tumor marker response is defined as at least a 50 percent reduction in tumor marker which must be confirmed and maintained for at least 4 weeks. Tumor marker response is assessed using cancer antigen (CA-125), carcinoembryonic antigen (CEA), CA-19.9 and other markers as available

The Hb response is defined by an increase of at least 1 gram per deciliter (g/dL) over baseline observed at least once in the absence of transfusion or erythropoietin stimulating agents.

The PFS is the time interval between first administration of siltuximab and the first documented sign of progression (at least a 20 percent increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new target or non-target lesions as per RECIST) or death, whichever occurs first.

The OS is the interval between first administration of siltuximab and the participant's death from any cause.

The EORTC QLQ-C30 is used to measure physical function, general health, and global health, as well as participant-reported impression of global quality of life. Symptoms in the scale include: fatigue, pain, and sleep disturbance. It contains 28 items scored using a Likert scale from 1 (not at all) to 4 (very much). 2 additional items are scored from 1 (very poor) to 7 (excellent). Total score ranges from 30-126 with higher score indicating better level of functioning or greater degree of symptoms.

The EORTC QLQ-OV28 covers side effects of therapy; activity limitation attributable to disease; hormonal symptoms; body image; difficulty with specific bodily functions; and sexual functioning. It contains 28 items scored using a Likert scale from 1 (not at all) to 4 (very much) with a recall period of the past week or, in the final segment, the past 4 weeks. Total score ranges from 28-112 with higher score indicating better level of functioning or greater degree of symptoms.

Area under the serum concentration versus time curve from time zero to infinity with extrapolation of the terminal phase will be calculated; samples for the determination of siltuximab serum concentration will be collected from 0 hour (h) (pre-dose) to 24h (post-dose) on Day (D) 1 up to Week 12 (Wk12) after last dose administration for all cohorts.

Area under the serum concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (AUC\[0-t\]) was calculated.

The Cmin,ss is the minimum observed serum concentration during a dosing interval at steady-state (time at which serum concentration does not change with time).

The Cmax is the maximum observed serum concentration of siltuximab.

Terminal elimination half-life is the time measured for the serum concentration to decrease to half value.

Total systemic CL is calculated by dividing the dose by area under the curve from time 0 to extrapolated infinite time (AUCinf).

The Vss is calculated by multiplying mean residence time (MRT) with systemic clearance (CL). MRT is the time when 63.2 percent of an intravenous dose has been eliminated after single dose administration.

The CRP levels are determined using high sensitive CRP assay and percent change from baseline is calculated at each time point.

Percent change from baseline in the levels of inflammatory (pertaining to pain, redness and swelling) markers for interferon gamma (IFN-g), interleukin 1 beta (IL1b), IL-2, IL-5, IL-8, IL10, IL12, and tumor necrosis factor alpha (TNFa) is calculated.

Percent change from baseline in the level of markers associated with angiogenesis related factors (vascular endothelial growth factor \[VEGF\], vascular endothelial growth factor receptor \[VEGFR\], and basic fibroblast growth factor \[bFGF\]) is calculated.

Percent change from baseline in the level of ligand-binding subunit of the IL-6R, soluble GP80 (sGP80) and signal-transducing subunit of the IL-6R, soluble GP130 (sGP130) is calculated.

Number of participants who are tested positive for antibodies (type of protein that helps to protect the body against foreign matter, such as bacteria and viruses) to siltuximab is reported.

Hepcidin is a liver-produced iron-regulatory peptide hormone (substance made by a gland in the body that regulates another part of the body) that is implicated in anemia (decreased number of red blood cells) of inflammation (pain, redness and swelling). Percent change from baseline in hepcidin (marker of anemia and iron metabolism) level is calculated.

Spots Global Cancer Trial Database for kras protein, human