A Phase I Clinical Trial to Investigate the Correlation Between UGT1A1 Genotype and Irinotecan (CPT-11) Pharmacokinetics and Toxicity in Cancer Patients
irinotecan hydrochloride
Lymphadenopathy+41
+ Chronic Disease
+ DNA Virus Infections
Treatment Study
Summary
Study start date: January 1, 1999
Actual date on which the first participant was enrolled.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. OUTLINE: Patients are genotyped for UGT1A1 enzyme and classified as "Gilbert's" (7/7), "heterozygotes" (6/7), and "homozygotes for allele 6" (6/6). The DNA is analyzed for the UGT1A1 coding region mutation (Gly71Arg) and CYP3A4 promoter polymorphism. Patients are also examined for glucuronidator ratio of SN-38, the active metabolite of irinotecan, and classified as "low/slow" (very low or zero SN-38G/SN-38 ratio), "intermediate" (less than 50% normal ratio), or "normal". 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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.60 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
Inclusion Criteria: 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
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.One single intervention group is designated in this study
This study does not include a placebo group
Treatment Groups
Group I
ExperimentalStudy Objectives
Primary Objectives
Secondary Objectives
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location
University of Chicago Comprehensive Cancer Center
Chicago, United StatesOpen University of Chicago Comprehensive Cancer Center in Google Maps