A Phase I Clinical Trial to Investigate the Correlation Between UGT1A1 Genotype and Irinotecan (CPT-11) Pharmacokinetics and Toxicity in Cancer Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Grade 3-4 diarrhea
研究概览
简要总结
Phase I trial to study genetic testing and the effectiveness of irinotecan in treating patients who have solid tumors and lymphoma. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Genetic testing for a specific enzyme may help doctors determine whether side effects from or response to chemotherapy are related to a person's genetic makeup
详细描述
OBJECTIVES:
I. Classify patients with solid tumors or lymphoma according to UGT1A1 promoter (TATA box) and coding region (Gly71Arg) mutation, and CYP3A4 promoter (G to A) polymorphisms.
II. Identify UGT1A1 enzyme glucuronidator and irinotecan oxidizer phenotypes in these patients and determine the correlation between the two metabolic reactions in vivo.
III. Determine the relationship between UGT1A1 genotype (promoter and/or coding region mutation) and CYP3A4 promoter genotype vs gastrointestinal or bone marrow toxicity, and pharmacokinetics of irinotecan in these patients.
IV. Determine the pharmacokinetics of irinotecan in these patients.
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
- •Histologically proven solid tumor or lymphoma
- •Responded to irinotecan OR no existing curative therapy
- •No leukemia
- •Measurable or evaluable disease
- •Performance status - Karnofsky 70-100%
- •WBC at least 3500/mm^3
- •Absolute neutrophil count at least 1500/mm^3
- •Platelet count at least 100,000/mm^3
- •Bilirubin normal
- •SGOT/SGPT less than 5 times upper limit of normal (unless due to disease)
- •Creatinine no greater than 1.5 mg/dL
- •Creatinine clearance at least 60 mL/min
- •Not pregnant or nursing
- •Fertile patients must use effective contraception
- •No inflammatory bowel disease requiring therapy
- •No chronic diarrhea syndrome or paralytic ileus
- •At least 2 weeks since prior colony stimulating factor
- •At least 4 weeks since prior biologic therapy
- •No concurrent biologic therapy
- •See Disease Characteristics
- •At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- •No other concurrent chemotherapy
- •At least 4 weeks since prior radiotherapy to greater than 25% of bone marrow
- •No concurrent palliative radiotherapy
- •No prior transplant
- •No concurrent substrates of UGT1A1 enzyme
- •No concurrent inducers or inhibitors of UGT1A1 enzyme activity
排除标准
- 未提供
研究组 & 干预措施
Treatment (irinotecan hydrochloride)
Patients receive irinotecan IV over 90 minutes once every 3 weeks. Treatment continues for at least 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: irinotecan hydrochloride (Drug)
结局指标
主要结局
Grade 3-4 diarrhea
时间窗: Up to 4 years
A Cochran-Armitage test for trend will be used to determine whether there is a linear trend in the proportion of patients within each genotype experiencing grade 3-4 diarrhea. Similarly, trend analysis will be performed to determine if there is a linear trend in the proportion of patients within each phenotype experiencing grade 3-4 myelosuppression. Genotype (3 ordered levels) will be modeled as a function of metabolic ratios and biliary index to determine whether these are independent.
次要结局
- Genotype(Up to 4 years)
- Phenotype(Up to 4 years)