A Phase I/II Study of a Chimeric Antibody Against Interleukin-6 (CNTO 328) in Subjects With Metastatic Renal Cell Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 68
- 主要终点
- Number of Patients With Tumor Response (Parts 2 and 3)
研究概览
简要总结
The purpose of this study is to better understand the safety, tolerability and distribution of CNTO 328 in the bloodstream.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
Part 1 (CNTO 328)
In Part 1 of the study, 4 intravenous infusions (IV) [injection of a substance into a vein] of CNTO 328 will be administered to patients in 4 dose levels ranging from 1, 3, 6, and 12 mg/kg on days 1, 29, 43, and 57 to determine the maximum tolerated dose for Part 2 of the study.
干预措施: CNTO 328 (Drug)
Part 2 (CNTO 328)
In Part 2 of the study, 2 well tolerated dose levels of CNTO 328 from Part 1 of the study will be administered every 3 weeks as 4 IV infusions to patients.
干预措施: CNTO 328 (Drug)
Part 3 (CNTO 328)
In Part 3 of the study, CNTO 328 at a dose level of 6 mg/kg will be administered as IV infusion every 2 weeks for at least 6 doses.
干预措施: CNTO 328 (Drug)
结局指标
主要结局
Number of Patients With Tumor Response (Parts 2 and 3)
时间窗: Up to Week 11
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.
Serum Concentration of CNTO 328 (Parts 1, 2, and 3)
时间窗: Pre dose, up to 6 weeks after the last dose
Number of Patients With Dose-limiting Toxicity as a Measure of Safety (Parts 1 and 3)
时间窗: Up to 6 weeks after the last dose
Number of Participants With Adverse Events (Parts 1, 2, and 3)
时间窗: Up to 6 weeks after the last dose
Change From Baseline in Interleukin-6 levels (Part 1)
时间窗: Within 2 weeks before first dose, pre dose, post dose (6 weeks after the last dose)
Change From Baseline in C-reactive Protein (Part 1)
时间窗: Within 2 weeks before first dose, pre dose, post dose (6 weeks after the last dose)
次要结局
- Number of Patients With an Overall Tumor Response (Parts 2 and 3)(Screening (3 weeks prior to first dose), Week 7, Week 11, and 6 weeks after the last dose)
- Serum Antibodies to CNTO 328 (Parts 1, 2, and 3)(Up to 6 weeks after the last dose)
- Time to disease progression (Parts 2 and 3)(Up to 6 weeks after the last dose)
- Number of Patients With Clinical Benefit (Parts 1, 2, and 3)(Up to 6 weeks after the last dose)
- Duration of Tumor Response (Parts 2 and 3)(Screening (3 weeks prior to first dose), Week 7, Week 11, and 6 weeks after the last dose)
- Change From Baseline in Quality of Life Measured Using Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue questionnaire (Parts 1, 2, and 3)(Within 2 weeks before dose, prior to first dose, Days 29, 43, 57, and 71, and 6 weeks after the last dose)
- Change From Baseline in C-reactive Protein (Parts 2 and 3)(Within 2 weeks before first dose, pre dose, post dose (6 weeks after the last dose))
- Change From Baseline in Interleukin-6 levels (Parts 2 and 3)(Within 2 weeks before first dose, pre dose, post dose (6 weeks after the last dose))