Trial Information

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

CNTO 328 is an antibody. An antibody is an important substance made by the body to fight
infection. IL-6 is found naturally in the body and it can promote the growth of cancer (CA)
cells. By blocking the activity of IL-6 in your body, CNTO 328 may slow down cancer growth.
This study is being conducted because the sponsor changed the production process of CNTO
328. This is the first time that this new CNTO 328 will be given to patients. The study
consists of two parts. In part 1, groups of patients are treated with different dose levels.
In part 2, the selected dose and schedule will be further explored in patients with specific
tumor types. The study tests the safety and effectiveness of the experimental drug, CNTO 328
in patients with advanced cancer. This study also tests how CNTO328 is cleared from your
body and how your body reacts to it. For this reason blood tests will be performed and some
characteristics of the tumor are analyzed. In Part 1, patients will be treated with
different dose levels. Dose Cohort 1: 2.8 mg/kg, once every 2 weeks (1 patient); Dose Cohort
2: 5.5 mg/kg, once every 2 weeks (3 patients); Dose Cohort 3: 11 mg/kg, once every 3 weeks
(6 patients); Dose Cohort 4: 15 or 8.3 mg/kg, once every 3 weeks (6 patients). Patients
will be evaluated for the occurrence of dose limiting toxicities (DLTs). Dose Cohort 5: up
to 20 patients with ovarian cancer or KRAS mutant tumors will be treated with the dose level
that is chosen based on the experience in cohort 1-4. Patients enrolling in Part 1 (Cohorts
1-4) will receive 4 administrations of CNTO 328 over a 10-13 week period. Patients enrolling
in Cohort 5 will receive 12 administrations over a 33 week period. The purpose of Part 1 of
the study is to determine the recommended dose of CNTO 328 in patients with malignant solid
tumors. The main purpose of the part 2 study is to estimate the clinical benefit of CNTO 328
monotherapy in patients with ovarian cancer and with KRAS mutant tumors. In Part 2, the
selected dose determined by Part 1 will be further explored in patients with specific tumor
types. Patients participating in Part 2 of the study will be administered the recommended
dose of CNTO 328 for 12 administrations over a 33 week period. Study participation for each
patient will continue for a maximum of 12 weeks after the last CNTO 328 administration. To
monitor the safety of the patients participating in this study, patients will be monitored
for adverse events (AEs) at every visit, and the following assessments will be performed
periodically: physical exam, vital signs (before and after CNTO328 administration), ECG
recording (before and after CNTO328 administration), blood draw to monitor organ function
and hematological parameters, urine analysis. The assessments will be performed weekly
during the first 4 weeks of the study and every 2-3 weeks thereafter. Once a patient
discontinues study treatment, follow up visits up to 12 weeks after last dose are scheduled.
Patients may then be contacted for up to one year after the last dose for follow-up survival
and disease status information. CNTO 328 is given by intravenous (IV) infusion; through a
tube directly into your vein over 1 hour. In Phase 1, cohorts 1-4, doses will be
administered in a range of 2.8-15 mg/kg. In Phase 2, cohort 5 will receive the recommended
dose and schedule as determined from cohorts 1-4. Patients enrolling in Phase 1 (Cohorts
1-4) will receive 4 administrations of CNTO 328 over a 10-13 week period, while patients
enrolling in Cohort 5 and Phase 2 will receive 12 administrations over a 33 week period.