A Study of CNTO 328 in Subjects With Metastatic Renal Cell Carcinoma

Centocor, Inc.68 enrolled

Overview

The purpose of this study is to better understand the safety, tolerability and distribution of CNTO 328 in the bloodstream.

This research study uses a type of drug called anti-IL-6 monoclonal antibody, also known as CNTO 328. CNTO 328 is a new experimental drug. This study is trying to better understand the safety, the tolerability (side effects), and the distribution of the drug in the blood stream. The effects of CNTO 328 in patients with renal cell carcinoma are currently unknown. However, recent data has shown that treatment with another anti-IL-6 monoclonal antibody reduces the symptoms of renal cell carcinoma. The study is divided in 3 parts. Part 1 is the phase I portion of the study and evaluated the safety of CNTO 328 in subjects with metastatic renal cell carcinoma. Part 2 and 3 will evaluate efficacy and safety of the drug in this patient population.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Carcinoma, Renal Cell

Interventions

CNTO 328DRUG

Patients will receive CNTO 328 at dose levels ranging from 1, 3, 6, and 12 mg/kg in Part 1 of the study to determine the maximum tolerated dose for Part 2 of the study. Patients will receive 2 well tolerated dose levels of CNTO 328 from Part 1 of the study every 3 weeks in Part 2 of the study. Patients will receive 6 mg/kg of CNTO 328 every 2 weeks in Part 3 of the study.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Clinical diagnosis (histologically confirmed, preferably) of metastatic renal cell carcinoma with documented metastases beyond the level of the regional lymphatics (ie, any T, any N, M1 disease) * Measurable or evaluable disease (Part 1); measurable disease (Part 2 and Part 3) * Documented disease progression based on objective tumor assessment (Part 2 and Part 3), proven by tumor measurements on 2 computerized tomography scans within 6 months prior to enrollment * Life expectancy greater than or equal to 6 months at screening * Serum C-reactive protein (CRP): detectable ( 4 mg/L or more) according to the standard assay of the core laboratory (Part 1 and Part 2); serum CRP detectable to 30 mg/L or more (Part 3) Exclusion Criteria: * Received any investigational drug within 30 days, whichever is longer * History of receiving murine or chimeric proteins or human/murine recombination products (such as BE8 and other anti-IL-6 monoclonal antibodies) * Serious concurrent illness or significant cardiac disease characterized by significant ischemic coronary disease or congestive heart failure * Chronic infection, prior history of recurrent infection, or clinically important active infection * Presence of a transplanted solid organ (with the exception of a corneal transplant more than 3 months prior to screening) or having received an allogeneic bone marrow transplant or peripheral blood stem cell transplant

Locations (14)

Unnamed facility

Brno, Czechia

Unnamed facility

Hradec nad Svitavou, Czechia

Unnamed facility

Caen, France

Unnamed facility

Lyon, France

Outcomes

Primary Outcomes

Number of Patients With Dose-limiting Toxicity as a Measure of Safety (Parts 1 and 3)

Time frame: Up to 6 weeks after the last dose

Number of Patients With Tumor Response (Parts 2 and 3)

Tumor response will be evaluated as sum of complete response (CR) and partial response (PR). CR is disappearance of all measurable and evaluable disease. No new lesions. No evidence of non evaluable disease. PR is 50% or more decrease from baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions.

Time frame: Up to Week 11

Serum Concentration of CNTO 328 (Parts 1, 2, and 3)

Time frame: Pre dose, up to 6 weeks after the last dose

Number of Participants With Adverse Events (Parts 1, 2, and 3)

Time frame: Up to 6 weeks after the last dose

Change From Baseline in C-reactive Protein (Part 1)

Time frame: Within 2 weeks before first dose, pre dose, post dose (6 weeks after the last dose)

Change From Baseline in Interleukin-6 levels (Part 1)

Time frame: Within 2 weeks before first dose, pre dose, post dose (6 weeks after the last dose)

Secondary Outcomes

Serum Antibodies to CNTO 328 (Parts 1, 2, and 3)

Serum levels of antibodies to CNTO 328 will be used to evaluate potential immunogenicity.

Time frame: Up to 6 weeks after the last dose

Number of Patients With Clinical Benefit (Parts 1, 2, and 3)

Clinical benefit will include assessment of pain (measured using Brief Pain Inventory which includes 4 items assessing pain intensity (pain intensity subscales) and 7 items assessing how much pain has interfered with daily activities (pain interference subscales). The pain intensity score is assessed with 4 questions rated on 11-point numerical rating scale (NRS) ranging from "0 = no pain" to "10 = higher severity of pain". The pain interference score is assessed with 7 questions rated on 11-point numerical rating scale (NRS) ranging from "0 = does not interfere" to "10 = completely interferes". Higher scores indicate worsening), functional impairment (assessed using Karnofsky performance status which quantifies patient's well-being and activities of daily life), weight change (assessed by change in body weight).

Data from ClinicalTrials.gov

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