Ovarian NeoplasmsPhase 1/2NCT00841191
A Safety, Efficacy and Pharmacokinetic Study of Siltuximab (CNTO 328) in Participants With Solid Tumors
A Phase 1/2 study testing CNTO 328; Anti-interleukin-6 monoclonal antibody in people with Ovarian Neoplasms and Pancreatic Neoplasms, run by Centocor, Inc. at 12 sites in 5 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ovarian Neoplasms, Pancreatic Neoplasms, Colorectal Neoplasms
- What is being tested?
- CNTO 328; Anti-interleukin-6 monoclonal antibody
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 84 participants
- Where
- 12 sitesin 5 countries
- Study dates
- Mar 2009to Apr 2011
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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 locations and contacts
12 sites in 5 countries.
12 sites in 5 countries
United Kingdom3 sites
Study site
Birmingham
Study site
Edinburgh
Study site
Southampton
United States2 sites
Study site
Houston, Texas
Study site
Philadelphia, Pennsylvania
About this study
Official title: 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 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.
Read the 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
- Being tested
- CNTO 328; Anti-interleukin-6 monoclonal antibody
- Keywords
- Resistant to anti-EGFR, Interleukin-6, Neoplasms by Histologic Type, Immunologic Factors, Mol Physiological Effects of Drugs, KRAS protein, human, CNTO 328
- Medical subject headings
- Ovarian Neoplasms, Pancreatic Neoplasms, Colorectal Neoplasms, Head and Neck Neoplasms, Lung Neoplasms, Neoplasms by Histologic Type
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CNTO 328; Anti-interleukin-6 monoclonal antibodyDrug
Also called Siltuximab
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 antibodyDrug
Also called Siltoximab
Siltuximab 5.5 mg/kg will be administered as 1-hour intravenous infusion on Day 1, Day 28, Day 42 and Day 56
CNTO 328; Anti-interleukin-6 monoclonal antibodyDrug
Also called Siltuximab
Siltuximab 11 mg/kg will be administered as 1-hour intravenous infusion on Day 1, Day 28, Day 49 and Day 70
CNTO 328; Anti-interleukin-6 monoclonal antibodyDrug
Also called Siltuximab
Siltuximab 15 mg/kg will be administered as 1-hour intravenous infusion on Day 1, Day 28, Day 49 and Day 70
CNTO 328; Anti-interleukin-6 monoclonal antibodyDrug
Also called Siltuximab
Siltuximab 15 mg/kg will be administered as 1-hour intravenous infusion once every 21 days for up to a total of 231 days
CNTO 328; Anti-interleukin-6 monoclonal antibodyDrug
Also called Siltuximab
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.
CNTO 328; Anti-interleukin-6 monoclonal antibodyDrug
Also called Siltuximab
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
| Study group | Role | What they receive |
|---|---|---|
| Siltuximab 2.8 mg/kg (Cohort 1) | Experimental | Not described Receives: Drug: CNTO 328; Anti-interleukin-6 monoclonal antibody |
| Siltuximab 5.5 mg/kg (Cohort 2) | Experimental | Not described Receives: Drug: CNTO 328; Anti-interleukin-6 monoclonal antibody |
| Siltuximab 11 mg/kg (Cohort 3) | Experimental | Not described Receives: Drug: CNTO 328; Anti-interleukin-6 monoclonal antibody |
| Siltuximab 15 mg/kg (Cohort 4) | Experimental | Not described Receives: Drug: CNTO 328; Anti-interleukin-6 monoclonal antibody |
| Siltuximab 15 mg/kg (Expansion Cohort 5) | Experimental | Not described Receives: Drug: CNTO 328; Anti-interleukin-6 monoclonal antibody |
| Siltuximab 15 mg/kg (Ovarian Cancer Cohort 6) | Experimental | Not described Receives: Drug: CNTO 328; Anti-interleukin-6 monoclonal antibody |
| Siltuximab 15 mg/kg (KRAS Mutant Tumors Cohort 7) | Experimental | Not described Receives: Drug: CNTO 328; Anti-interleukin-6 monoclonal antibody |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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
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
Measured: 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
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.
Measured: Baseline up to Week 4 after last dose administration
Progression Free Survival (PFS)
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.
Measured: Baseline until disease progression or death, assessed every 9 weeks up to Week 4 after last dose administration
Overall Survival (OS)
The OS is the interval between first administration of siltuximab and the participant's death from any cause.
Measured: From first dose administration until death, assessed every 3 months up to 12 months after last dose administration
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score
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.
Measured: Baseline up to 4 weeks after last dose administration
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-OV28) Score at Week 4 After Last Dose Administration
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.
Measured: Baseline and Week 4 after last dose administration
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf])
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.
Measured: Cohort1-4:0,1,4,6,24h post-dose on D1,8,15,22; D1 of extended treatment; Cohort1,2:0,1h post-dose on D28,42,56; Cohort3,4:D28,49,70; Cohort5-7:0,1,2h post-dose on D1,8,15; 0,1h post-dose on D21,42,63,84,105,168,231; up to Wk12 after last dose (Cohort1-7)
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC[0-t])
Area under the serum concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (AUC[0-t]) was calculated.
Measured: Cohort1-4:0,1,4,6,24h post-dose on D1,8,15,22; D1 of extended treatment; Cohort1,2:0,1h post-dose on D28,42,56; Cohort3,4:D28,49,70; Cohort5-7:0,1,2h post-dose on D1,8,15; 0,1h post-dose on D21,42,63,84,105,168,231; up to Wk12 after last dose (Cohort1-7)
Minimum Observed Serum Concentration at Steady-State (Cmin,ss)
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).
Measured: Cohort1-4:0,1,4,6,24h post-dose on D1,8,15,22; D1 of extended treatment; Cohort1,2:0,1h post-dose on D28,42,56; Cohort3,4:D28,49,70; Cohort5-7:0,1,2h post-dose on D1,8,15; 0,1h post-dose on D21,42,63,84,105,168,231; up to Wk12 after last dose (Cohort1-7)
Maximum Observed Serum Concentration (Cmax)
The Cmax is the maximum observed serum concentration of siltuximab.
Measured: Cohort1-4:0,1,4,6,24h post-dose on D1,8,15,22; D1 of extended treatment; Cohort1,2:0,1h post-dose on D28,42,56; Cohort3,4:D28,49,70; Cohort5-7:0,1,2h post-dose on D1,8,15; 0,1h post-dose on D21,42,63,84,105,168,231; up to Wk12 after last dose (Cohort1-7)
Terminal Elimination Half Life (t1/2)
Terminal elimination half-life is the time measured for the serum concentration to decrease to half value.
Measured: Cohort1-4:0,1,4,6,24h post-dose on D1,8,15,22; D1 of extended treatment; Cohort1,2:0,1h post-dose on D28,42,56; Cohort3,4:D28,49,70; Cohort5-7:0,1,2h post-dose on D1,8,15; 0,1h post-dose on D21,42,63,84,105,168,231; up to Wk12 after last dose (Cohort1-7)
Total Systemic Clearance (CL)
Total systemic CL is calculated by dividing the dose by area under the curve from time 0 to extrapolated infinite time (AUCinf).
Measured: Cohort1-4:0,1,4,6,24h post-dose on D1,8,15,22; D1 of extended treatment; Cohort1,2:0,1h post-dose on D28,42,56; Cohort3,4:D28,49,70; Cohort5-7:0,1,2h post-dose on D1,8,15; 0,1h post-dose on D21,42,63,84,105,168,231; up to Wk12 after last dose (Cohort1-7)
Volume of Distribution at Steady State (Vss)
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.
Measured: Cohort1-4:0,1,4,6,24h post-dose on D1,8,15,22; D1 of extended treatment; Cohort1,2:0,1h post-dose on D28,42,56; Cohort3,4:D28,49,70; Cohort5-7:0,1,2h post-dose on D1,8,15; 0,1h post-dose on D21,42,63,84,105,168,231; up to Wk12 after last dose (Cohort1-7)
Percent Change From Baseline in C-Reactive Protein (CRP) Level
The CRP levels are determined using high sensitive CRP assay and percent change from baseline is calculated at each time point.
Measured: Baseline; Day (D) 1,8,15 (post-dose) for cohort 1 to 7; Day 22 (post-dose), 28 (pre-dose) for cohort 1 to 4; Day 42,56 (pre-dose) for cohort 1, 2; Day 49,70 (pre-dose) for cohort 3, 4; Day 21,42,63,84,105,126,147,168,189,210 (pre-dose) for cohort 5 to 7
Percent Change From Baseline in Inflammatory Cytokines Level
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.
Measured: Baseline; Day 8 and 15 (post-dose) for cohort (C) 1 to 7; Day 22 (post-dose) and 28 (pre-dose) for cohort 1 to 4; Day 42 and 56 (pre-dose) for cohort 1 and 2; Day 49 and 70 (pre-dose) for cohort 3 and 4; Day 21, 42 and 63 (pre-dose) for cohort 5 to 7
Percent Change From Baseline in the Angiogenesis Related Factors Level
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.
Measured: Baseline; Day 8 and 15 (post-dose) for cohort 1 to 7; Day 22 (post-dose) and 28 (pre-dose) for cohort 1 to 4; Day 42 and 56 (pre-dose) for cohort 1 and 2; Day 49 and 70 (pre-dose) for cohort 3 and 4; Day 21, 42 and 63 (pre-dose) for cohort 5 to 7
Percent Change From Baseline in Interleukin 6 Receptor (IL-6R) Subunits Level
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.
Measured: Baseline; Day 8 and 15 (post-dose) for cohort 1 to 7; Day 28 (pre-dose) for cohort 1 to 4; Day 42 and 56 (pre-dose) for cohort 1 and 2; Day 49 and 70 (pre-dose) for cohort 3 and 4; Day 21, 42 and 63 (pre-dose) for cohort 5 to 7
Number of Participants Assessed Positive for Antibodies to Siltuximab
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.
Measured: Day 1 (pre-dose) up to Week 12 after last dose administration
Percent Change From Baseline in Hepcidin Level
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.
Measured: Baseline; Day 8 and 15 (post-dose) for cohort 1 to 7; Day 22 (post-dose) and 28 (pre-dose) for cohort 1 to 4; Day 42 and 56 (pre-dose) for cohort 1 and 2; Day 49 and 70 (pre-dose) for cohort 3 and 4; Day 21, 42 and 63 (pre-dose) for cohort 5 to 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2009 (estimated)
- Study startMar 2009
- Primary completionApr 2011
- Study completionApr 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ovarian NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centocor, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Centocor, Inc. Clinical Trial, Study director, Centocor, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00841191
- Sponsor's protocol ID
- CR015580
- Other IDs
- CNTO328STM2001, 2008-005180-33, 2008
- Status last verified
- May 2014
- First submitted
- 9 Feb 2009
- Last updated
- 14 May 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00841191
- Acronym / sponsor ID
- CR015580
- Conditions
- Ovarian Neoplasms, Pancreatic Neoplasms, Colorectal Neoplasms, Head and Neck Neoplasms, Lung Neoplasms
- Keywords
- Resistant to anti-EGFR, Interleukin-6, Neoplasms by Histologic Type, Immunologic Factors, Mol Physiological Effects of Drugs, KRAS protein, human, CNTO 328
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- Centocor, Inc.Industry (pharma, biotech, devices)
- Study start
- Mar 2009
- Primary completion
- Apr 2011 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 11 Feb 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Siltuximab 2.8 mg/kg (Cohort 1) | Experimental | Drug: CNTO 328; Anti-interleukin-6 monoclonal antibody |
| Siltuximab 5.5 mg/kg (Cohort 2) | Experimental | Drug: CNTO 328; Anti-interleukin-6 monoclonal antibody |
| Siltuximab 11 mg/kg (Cohort 3) | Experimental | Drug: CNTO 328; Anti-interleukin-6 monoclonal antibody |
| Siltuximab 15 mg/kg (Cohort 4) | Experimental | Drug: CNTO 328; Anti-interleukin-6 monoclonal antibody |
| Siltuximab 15 mg/kg (Expansion Cohort 5) | Experimental | Drug: CNTO 328; Anti-interleukin-6 monoclonal antibody |
| Siltuximab 15 mg/kg (Ovarian Cancer Cohort 6) | Experimental | Drug: CNTO 328; Anti-interleukin-6 monoclonal antibody |
| Siltuximab 15 mg/kg (KRAS Mutant Tumors Cohort 7) | Experimental | Drug: CNTO 328; Anti-interleukin-6 monoclonal antibody |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CNTO 328; Anti-interleukin-6 monoclonal antibodyAlso: SiltuximabSiltuximab 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 | Drug | Siltuximab 2.8 mg/kg (Cohort 1) |
| CNTO 328; Anti-interleukin-6 monoclonal antibodyAlso: SiltoximabSiltuximab 5.5 mg/kg will be administered as 1-hour intravenous infusion on Day 1, Day 28, Day 42 and Day 56 | Drug | Siltuximab 5.5 mg/kg (Cohort 2) |
| CNTO 328; Anti-interleukin-6 monoclonal antibodyAlso: SiltuximabSiltuximab 11 mg/kg will be administered as 1-hour intravenous infusion on Day 1, Day 28, Day 49 and Day 70 | Drug | Siltuximab 11 mg/kg (Cohort 3) |
| CNTO 328; Anti-interleukin-6 monoclonal antibodyAlso: SiltuximabSiltuximab 15 mg/kg will be administered as 1-hour intravenous infusion on Day 1, Day 28, Day 49 and Day 70 | Drug | Siltuximab 15 mg/kg (Cohort 4) |
| CNTO 328; Anti-interleukin-6 monoclonal antibodyAlso: SiltuximabSiltuximab 15 mg/kg will be administered as 1-hour intravenous infusion once every 21 days for up to a total of 231 days | Drug | Siltuximab 15 mg/kg (Expansion Cohort 5) |
| CNTO 328; Anti-interleukin-6 monoclonal antibodyAlso: SiltuximabSiltuximab 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. | Drug | Siltuximab 15 mg/kg (Ovarian Cancer Cohort 6) |
| CNTO 328; Anti-interleukin-6 monoclonal antibodyAlso: SiltuximabSiltuximab 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 | Drug | Siltuximab 15 mg/kg (KRAS Mutant Tumors Cohort 7) |
Primary outcome
Percentage of Participants With Clinical Benefit Response (CBR)
Time frame: Baseline until disease progression or withdrawal of consent, assessed every 9 weeks up to Week 4 after last dose administration
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.
20 secondary outcomes
Percentage of Participants With Overall Response
Time frame: 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
Time frame: 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
Time frame: Baseline up to Week 4 after last dose administration
Progression Free Survival (PFS)
Time frame: Baseline until disease progression or death, assessed every 9 weeks up to Week 4 after last dose administration
Overall Survival (OS)
Time frame: From first dose administration until death, assessed every 3 months up to 12 months after last dose administration
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score
Time frame: Baseline up to 4 weeks after last dose administration
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-OV28) Score at Week 4 After Last Dose Administration
Time frame: Baseline and Week 4 after last dose administration
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf])
Time frame: Cohort1-4:0,1,4,6,24h post-dose on D1,8,15,22; D1 of extended treatment; Cohort1,2:0,1h post-dose on D28,42,56; Cohort3,4:D28,49,70; Cohort5-7:0,1,2h post-dose on D1,8,15; 0,1h post-dose on D21,42,63,84,105,168,231; up to Wk12 after last dose (Cohort1-7)
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC[0-t])
Time frame: Cohort1-4:0,1,4,6,24h post-dose on D1,8,15,22; D1 of extended treatment; Cohort1,2:0,1h post-dose on D28,42,56; Cohort3,4:D28,49,70; Cohort5-7:0,1,2h post-dose on D1,8,15; 0,1h post-dose on D21,42,63,84,105,168,231; up to Wk12 after last dose (Cohort1-7)
Minimum Observed Serum Concentration at Steady-State (Cmin,ss)
Time frame: Cohort1-4:0,1,4,6,24h post-dose on D1,8,15,22; D1 of extended treatment; Cohort1,2:0,1h post-dose on D28,42,56; Cohort3,4:D28,49,70; Cohort5-7:0,1,2h post-dose on D1,8,15; 0,1h post-dose on D21,42,63,84,105,168,231; up to Wk12 after last dose (Cohort1-7)
Maximum Observed Serum Concentration (Cmax)
Time frame: Cohort1-4:0,1,4,6,24h post-dose on D1,8,15,22; D1 of extended treatment; Cohort1,2:0,1h post-dose on D28,42,56; Cohort3,4:D28,49,70; Cohort5-7:0,1,2h post-dose on D1,8,15; 0,1h post-dose on D21,42,63,84,105,168,231; up to Wk12 after last dose (Cohort1-7)
Terminal Elimination Half Life (t1/2)
Time frame: Cohort1-4:0,1,4,6,24h post-dose on D1,8,15,22; D1 of extended treatment; Cohort1,2:0,1h post-dose on D28,42,56; Cohort3,4:D28,49,70; Cohort5-7:0,1,2h post-dose on D1,8,15; 0,1h post-dose on D21,42,63,84,105,168,231; up to Wk12 after last dose (Cohort1-7)
Total Systemic Clearance (CL)
Time frame: Cohort1-4:0,1,4,6,24h post-dose on D1,8,15,22; D1 of extended treatment; Cohort1,2:0,1h post-dose on D28,42,56; Cohort3,4:D28,49,70; Cohort5-7:0,1,2h post-dose on D1,8,15; 0,1h post-dose on D21,42,63,84,105,168,231; up to Wk12 after last dose (Cohort1-7)
Volume of Distribution at Steady State (Vss)
Time frame: Cohort1-4:0,1,4,6,24h post-dose on D1,8,15,22; D1 of extended treatment; Cohort1,2:0,1h post-dose on D28,42,56; Cohort3,4:D28,49,70; Cohort5-7:0,1,2h post-dose on D1,8,15; 0,1h post-dose on D21,42,63,84,105,168,231; up to Wk12 after last dose (Cohort1-7)
Percent Change From Baseline in C-Reactive Protein (CRP) Level
Time frame: Baseline; Day (D) 1,8,15 (post-dose) for cohort 1 to 7; Day 22 (post-dose), 28 (pre-dose) for cohort 1 to 4; Day 42,56 (pre-dose) for cohort 1, 2; Day 49,70 (pre-dose) for cohort 3, 4; Day 21,42,63,84,105,126,147,168,189,210 (pre-dose) for cohort 5 to 7
Percent Change From Baseline in Inflammatory Cytokines Level
Time frame: Baseline; Day 8 and 15 (post-dose) for cohort (C) 1 to 7; Day 22 (post-dose) and 28 (pre-dose) for cohort 1 to 4; Day 42 and 56 (pre-dose) for cohort 1 and 2; Day 49 and 70 (pre-dose) for cohort 3 and 4; Day 21, 42 and 63 (pre-dose) for cohort 5 to 7
Percent Change From Baseline in the Angiogenesis Related Factors Level
Time frame: Baseline; Day 8 and 15 (post-dose) for cohort 1 to 7; Day 22 (post-dose) and 28 (pre-dose) for cohort 1 to 4; Day 42 and 56 (pre-dose) for cohort 1 and 2; Day 49 and 70 (pre-dose) for cohort 3 and 4; Day 21, 42 and 63 (pre-dose) for cohort 5 to 7
Percent Change From Baseline in Interleukin 6 Receptor (IL-6R) Subunits Level
Time frame: Baseline; Day 8 and 15 (post-dose) for cohort 1 to 7; Day 28 (pre-dose) for cohort 1 to 4; Day 42 and 56 (pre-dose) for cohort 1 and 2; Day 49 and 70 (pre-dose) for cohort 3 and 4; Day 21, 42 and 63 (pre-dose) for cohort 5 to 7
Number of Participants Assessed Positive for Antibodies to Siltuximab
Time frame: Day 1 (pre-dose) up to Week 12 after last dose administration
Percent Change From Baseline in Hepcidin Level
Time frame: Baseline; Day 8 and 15 (post-dose) for cohort 1 to 7; Day 22 (post-dose) and 28 (pre-dose) for cohort 1 to 4; Day 42 and 56 (pre-dose) for cohort 1 and 2; Day 49 and 70 (pre-dose) for cohort 3 and 4; Day 21, 42 and 63 (pre-dose) for cohort 5 to 7
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2014.
- 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 TumorsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Centocor, Inc. Clinical Trial study director
Centocor, Inc.
12 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CNTO 328; Anti-interleukin-6 monoclonal antibody in people with Ovarian Neoplasms and Pancreatic Neoplasms, run by Centocor, Inc. at 12 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in France, United Kingdom, United States, Belgium, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Clinical Benefit Response (CBR) (time frame: Baseline until disease progression or withdrawal of consent, assessed every 9 weeks up to Week 4 after last dose administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2014; AzTrials last refreshed its copy on 8 Nov 2026.