A Phase I Study Of LMB-9, A Recombinant Disulfide Stabilized Anti-Lewis Y Immonutoxin Administered By 5-Days Continuous Infusion For Patients With Colorectal Adenocarcinoma
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 50
- 试验地点
- 2
研究概览
简要总结
RATIONALE: LMB-9 immunotoxin can locate tumor cells and kill them without harming normal cells. This may be an effective treatment for advanced pancreatic, esophageal, stomach, colon or rectal cancer.
PURPOSE: Phase I trial to study the effectiveness of LMB-9 immunotoxin in treating patients who have advanced pancreatic, esophageal, stomach, colon, or rectal cancer.
详细描述
OBJECTIVES:
- Determine the toxicity of LMB-9 immunotoxin in patients with advanced adenocarcinoma of the colon, rectum, pancreas, esophagus, or stomach with overexpression of the Lewis-Y antigen.
- Determine the maximum tolerated dose of this drug in these patients.
- Determine the clinical response of patients treated with this drug.
- Determine the pharmacokinetics of this drug in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive LMB-9 immunotoxin IV continuously on days 1-5. Patients with stable or responding disease after completion of the first course receive additional courses every 4-5 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of LMB-9 immunotoxin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
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
- •DISEASE CHARACTERISTICS:
- •Histologically or cytologically confirmed advanced adenocarcinoma of the colon, rectum, pancreas, esophagus, or stomach that is refractory to standard treatment
- •Overexpression of the Lewis-Y antigen
- •Measurable or evaluable disease
- •No CNS metastasis
- •Metastatic liver disease from primary tumor allowed
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status:
- •Life expectancy:
- •At least 3 months
- •Hematopoietic:
- •Platelet count greater than 100,000/mm^3
- •Absolute granulocyte count greater than 1,200/mm^3
- •Bilirubin normal
- •SGOT and SGPT no greater than 1.5 times upper limit of normal
- •Hepatitis B or C antigen negative
- •No liver disease (e.g., alcohol liver disease)
- •Albumin at least 3.0 g/dL
- •Creatinine no greater than 1.4 mg/dL
- •Creatinine clearance at least 60 mL/min
- •Proteinuria no greater than 1 g/24 hours (grade II toxicity-like)
- •Cardiovascular:
- •No prior coronary artery disease
- •No New York Heart Association class II, III, or IV congestive heart failure
- •No arrhythmia requiring treatment
- •FEV_1 and FVC greater than 65% predicted
- •No other concurrent malignancy
- •No active peptic ulcer disease
- •No known allergy to omeprazole
- •No known seizure disorder
- •No concurrent medical or psychiatric condition that would preclude study participation
- •No contraindication to pressor therapy
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy:
- •Not specified
- •Chemotherapy:
- •At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
- •Endocrine therapy:
- •At least 3 weeks since prior hormonal therapy
- •Radiotherapy:
- •At least 3 weeks since prior radiotherapy and recovered
- •Not specified
排除标准
- 未提供