Phase I/II Study of 131I-Labeled Chimeric Antibody G250 (131I-cG250) in Patients With Advanced Renal Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Number of Patients With Adverse Events (AEs)
研究概览
简要总结
RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.
PURPOSE: Phase I/II trial to study the effectiveness of monoclonal antibody therapy in treating patients with advanced kidney cancer.
详细描述
This is a dose-escalation study. Initially patients receive a scout dose of iodine-131 radiolabeled chimeric monoclonal antibody G250 (131I-cG250) administered intravenously (IV) over 10 minutes to determine whole body clearance. One week later, patients receive incremental doses of 131I-cG250 IV over 10 minutes at 2-3 day intervals for 2-6 weeks,. Dose escalation begins at least 8 weeks after the last infusion of 131I-cG250. In the absence of dose-limiting toxicity in the first 3 patients treated, subsequent cohorts of 3 patients each receive escalating doses of 131I-cG250 on the same schedule. If dose-limiting toxicity occurs in 2 of 6 patients treated at a given dose level, then dose escalation ceases and the next lower dose is declared the maximum tolerated dose (MTD). Treatment continues once recovery from all toxic effects occurs, beginning 8 to 12 weeks following the last dose of 131I-cG250. Patients achieving complete remission, partial remission, or stable disease were eligible to receive up to 3 courses of treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically proven renal cell carcinoma. Clinical presentation consistent with metastatic renal cell carcinoma. Bidimensionally measurable disease by conventional imaging. Patients must have been off chemotherapy or immunotherapy for at least 6 weeks prior to study entry.
- •Women of child-bearing age must have had a negative pregnancy test carried out the day of and prior to receiving therapy, and were asked to use effective contraception during the study.
- •Patients were required to be ambulatory with a Karnofsky Performance Status at least 70, Serum creatinine ≤ 2mg/dl, Serum bilirubin ≤ 1mg/d, White Blood Cells (WBC) ≥ 3,500/mm^3, Platelet count ≥ 100,000/mm^3, Prothrombin time < 1.3 x control.
排除标准
- •Significant prior radiation therapy to the entire pelvis and/or lumbosacral spine.
- •Clinically significant cardiac disease. Serious infection requiring treatment with antibiotics, or other serious illness.
- •Women who are pregnant or lactating. Central Nervous System (CNS) tumor involvement. Life expectancy less than 6 weeks. Hypercalcemia greater than 12.5 mg/dL or symptomatic.
研究组 & 干预措施
Cohort 1 50cGy radiation
On day 1, patients received a single dose of 131I-cG250 (5 mCi/5 mg) administered as an intravenous infusion over 10 minutes.
Therapeutic doses of 131I-cG250 were administered the following week as fractionated outpatient doses, starting with 30 millicurie (mCi)/5 mg 131I-cG250. Subsequent doses of 131I-cG250 were administered at 2-3 day intervals with the total amount of 131I-cG250 administered based on the calculated clearance of the initial dose administered on day 1. Whole body activity was maintained at no more than 30 mCi iodine-131.
In the absence of disease progression and after recovery from toxicity, patients could be re-treated beginning 8 weeks after the last treatment of the initial series, for a total of not more than 3 treatments.
干预措施: Iodine-131 radiolabeled chimeric monoclonal antibody G250 (131I-cG250) (Biological)
Cohort 2 75cGy radiation
On day 1, patients received a single dose of 131I-cG250 (5 mCi/5 mg) administered as an intravenous infusion over 10 minutes.
Therapeutic doses of 131I-cG250 were administered the following week as fractionated outpatient doses, starting with 30 millicurie (mCi)/5 mg 131I-cG250. Subsequent doses of 131I-cG250 were administered at 2-3 day intervals with the total amount of 131I-cG250 administered based on the calculated clearance of the initial dose administered on day 1. Whole body activity was maintained at no more than 30 mCi iodine-131.
In the absence of disease progression and after recovery from toxicity, patients could be re-treated beginning 8 weeks after the last treatment of the initial series, for a total of not more than 3 treatments.
干预措施: Iodine-131 radiolabeled chimeric monoclonal antibody G250 (131I-cG250) (Biological)
Cohort 3 100cGy radiation
On day 1, patients received a single dose of 131I-cG250 (5 mCi/5 mg) administered as an intravenous infusion over 10 minutes.
Therapeutic doses of 131I-cG250 were administered the following week as fractionated outpatient doses, starting with 30 millicurie (mCi)/5 mg 131I-cG250. Subsequent doses of 131I-cG250 were administered at 2-3 day intervals with the total amount of 131I-cG250 administered based on the calculated clearance of the initial dose administered on day 1. Whole body activity was maintained at no more than 30 mCi iodine-131.
In the absence of disease progression and after recovery from toxicity, patients could be re-treated beginning 8 weeks after the last treatment of the initial series, for a total of not more than 3 treatments.
干预措施: Iodine-131 radiolabeled chimeric monoclonal antibody G250 (131I-cG250) (Biological)
结局指标
主要结局
Number of Patients With Adverse Events (AEs)
时间窗: Up to 12 months
All adverse events occurring during the study were to be recorded on the patient's case report form, and include the following information: a description; date of onset and resolution; severity; relationship to an investigational agent; action taken and outcome. Toxicity was graded in accordance with the NCI CTCAE version 3.0.
Number of Patients With Dose-Limiting Toxicities (DLTs)
时间窗: up to 12 months
Subjects were monitored for Adverse Events (AEs) for at least 8 weeks after the last infusion of 131I-cG250, or until recovery from all toxicity, and prior to dose escalation. Toxicity was graded in accordance with the Common Toxicity Criteria (CTC) of the National Cancer Institute (NCI) Version 3.0. Dose-Limiting Toxicity (DLT) was defined as grade 3 or greater toxicity related to study therapy. The maximum tolerated dose was defined as the highest safely tolerated dose where at most one of six patients experiences a DLT with the next higher dose having at least two patients who experience a DLT.
次要结局
- Number of Patients With Best Overall Tumor Response(Up to 12 weeks)
- Number of Patients With Human Anti-chimeric Antibodies (HACA)(Up to 6 months)