Phase I Study of LMB-9, a Recombinant Disulfide Stabilized Anti-Lewis Y Immunotoxin Admistered by Continuous Infusion
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 2
研究概览
简要总结
Phase I trial to study the effectiveness of LMB-9 immunotoxin in treating patients who have advanced colon, breast, non-small cell lung, bladder, pancreatic, or ovarian cancer. The LMB-9 immunotoxin can locate tumor cells and kill them without harming normal cells.
详细描述
OBJECTIVES:
I. Determine the maximum tolerated dose of LMB-9 immunotoxin in patients with advanced colon, breast, non-small cell lung, bladder, pancreas, or ovarian cancer.
II. Assess the toxicity and pharmacokinetics of this treatment regimen in these patients.
III. Determine the clinical responses in patients treated with this regimen.
OUTLINE: This is a dose-escalation study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •DISEASE CHARACTERISTICS:
- •Histologically or cytologically confirmed advanced colon, breast, non-small cell lung, bladder, pancreas, or ovarian cancer refractory to standard treatment or for which no effective standard therapy exists
- •Expresses Lewis Y antigen
- •Evidence of disease progression
- •B3 antigen on the surface of more than 30% of the tumor cells determined by immunohistochemistry
- •No neutralizing antibodies to LMB-9 immunotoxin
- •No untreated CNS metastases
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Male or female
- •Performance status:
- •Life expectancy:
- •At least 3 months
- •Hematopoietic:
- •Absolute granulocyte count greater than 1,200/mm^3
- •Platelet count greater than 100,000/mm^3
- •Bilirubin no greater than 1.5 times normal
- •SGOT and SGPT no greater than 2.5 times upper limit of normal (liver metastases allowed)
- •Albumin at least 3.0 g/dL
- •No prior liver disease (e.g., alcohol liver disease)
- •Hepatitis B and C negative
- •Creatinine no greater than 1.4 mg/dL
- •Creatinine clearance greater than 60 mL/min
- •Proteinuria less than 1 g/24 hours
- •Cardiovascular:
- •No history of coronary artery disease
- •No cardiac arrhythmia requiring therapy
- •No New York Heart Association class II-IV congestive heart failure
- •Pulmonary function test required if significant smoking history, possible pulmonary disease, or lung cancer
- •FEV1 and FVC at least 65% predicted
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No known seizure disorders
- •No urinary tract infection
- •No other concurrent malignancy
- •No active peptic ulcer disease
- •No known allergy to omeprazole
- •No contraindication to pressor therapy
- •No other concurrent medical or psychological condition that would preclude study
- •PRIOR CONCURRENT THERAPY:
- •Chemotherapy:
- •At least 3 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered
- •Endocrine therapy:
- •At least 3 weeks since prior hormonal therapy
- •Radiotherapy:
- •At least 3 weeks since prior radiotherapy and recovered
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive LMB-9 immunotoxin IV continuously for 10 days. Treatment continues every 30 days 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 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
干预措施: LMB-9 immunotoxin (Biological)