Phase I Study of Humanized 3S193 (Anti-Lewis-Y) Antibody in Patients With Advanced Colorectal Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Number of Patients With Dose-limiting Toxicities (DLTs)
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 trial to study the effectiveness of monoclonal antibody therapy in treating patients who have advanced colorectal cancer.
详细描述
OBJECTIVES:
- Determine the toxicity, maximum tolerated dose, and pharmacokinetics of monoclonal antibody hu3S193 in patients with advanced colorectal carcinoma.
- Determine the immune response in these patients treated with this regimen.
OUTLINE: This is a dose escalation study.
Patients receive monoclonal antibody hu3S193 (mAb hu3S193) IV over 30 minutes to 4 hours weekly for 8 weeks followed by 2 weeks of rest. Patients with stable or responding disease at week 10 receive maintenance mAb hu3S193 weekly. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of mAb hu3S193 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 patients experience dose limiting toxicities.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically proven stage IV colorectal carcinoma.
- •Failed or refused conventional chemotherapy.
- •Lewis Y antigen present on more than 50% of tumor cells.
- •Measurable or evaluable disease.
- •No central nervous system (CNS) tumor involvement.
- •Karnofsky 80-100%.
- •Life expectancy: At least 6 weeks.
- •Granulocyte count greater than 1,500/mm^
- •Platelet count greater than 100,000/mm^
- •Bilirubin no greater than 1.0 mg/dL.
- •Prothrombin time less than 3 times upper limit of normal.
- •Creatinine no greater than 1.4 mg/dL.
- •Female patients of childbearing age and male patients must be asked to use effective contraception during the study.
- •At least 4 weeks since other prior immunotherapy.
排除标准
- •New York Heart Association class III or IV heart disease.
- •Serious infection requiring antibiotics or other serious illness.
- •Pregnancy or nursing.
- •History of bleeding gastric ulcers or pancreatitis.
- •Diabetes mellitus requiring insulin.
- •Human antimouse antibodies (HAMA).
- •No prior mouse monoclonal antibody or antibody fragments.
- •Illness requiring the use of steroids or other anti-inflammatory agents.
- •Positive anti-hu3S193 antibody (HAHA) titer.
研究组 & 干预措施
Hu3S193 10 mg/m2
Hu3S193 was administered weekly for 8 consecutive weeks. The antibody was diluted in physiologic saline containing 5% human serum albumin and infused intravenously at a maximum rate of 100 mg/hour. If patients were stable or responding, they were eligible to receive 8-week maintenance cycles of hu3S193 at 10 mg/m2 starting in week 10 and continuing until progression.
干预措施: monoclonal antibody hu3S193 (Biological)
Hu3S193 25 mg/m2
Hu3S193 was administered weekly for 8 consecutive weeks. The antibody was diluted in physiologic saline containing 5% human serum albumin and infused intravenously at a maximum rate of 100 mg/hour. If patients were stable or responding, they were eligible to receive 8-week maintenance cycles of hu3S193 at 10 mg/m2 starting in week 10 and continuing until progression.
干预措施: monoclonal antibody hu3S193 (Biological)
Hu3S193 50 mg/m2
Hu3S193 was administered weekly for 8 consecutive weeks. The antibody was diluted in physiologic saline containing 5% human serum albumin and infused intravenously at a maximum rate of 100 mg/hour. If patients were stable or responding, they were eligible to receive 8-week maintenance cycles of hu3S193 at 10 mg/m2 starting in week 10 and continuing until progression.
干预措施: monoclonal antibody hu3S193 (Biological)
Hu3S193 100 mg/m2
Hu3S193 was administered weekly for 8 consecutive weeks. The antibody was diluted in physiologic saline containing 5% human serum albumin and infused intravenously at a maximum rate of 100 mg/hour. If patients were stable or responding, they were eligible to receive 8-week maintenance cycles of hu3S193 at 10 mg/m2 starting in week 10 and continuing until progression.
干预措施: monoclonal antibody hu3S193 (Biological)
Hu3S193 200 mg/m2
Hu3S193 was administered weekly for 8 consecutive weeks. The antibody was diluted in physiologic saline containing 5% human serum albumin and infused intravenously at a maximum rate of 100 mg/hour. If patients were stable or responding, they were eligible to receive 8-week maintenance cycles of hu3S193 at 10 mg/m2 starting in week 10 and continuing until progression.
干预措施: monoclonal antibody hu3S193 (Biological)
结局指标
主要结局
Number of Patients With Dose-limiting Toxicities (DLTs)
时间窗: up to 10 weeks.
Toxicity was graded in accordance with the Common Toxicity Scale developed by NCI (1998) where Grade 1 represents the lowest toxicity grade and Grade 5 death. Dose-limiting toxicity (DLT) was defined as Grade 3 and Grade 4 adverse events which were at least possibly related to study treatment.
次要结局
- Number of Patients With Tumor Responses(8 weeks)