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Genetic Testing Plus Irinotecan in Treating Patients With Solid Tumors or Lymphoma
This study has been completed.
Study NCT00003970   Information provided by National Cancer Institute (NCI)
First Received: November 1, 1999   Last Updated: February 6, 2009   History of Changes

November 1, 1999
February 6, 2009
January 1999
 
 
 
Complete list of historical versions of study NCT00003970 on ClinicalTrials.gov Archive Site
 
 
 
Genetic Testing Plus Irinotecan in Treating Patients With Solid Tumors or Lymphoma
A Phase I Clinical Trial to Investigate the Correlation Between UGT1A1 Genotype and Irinotecan (CPT-11) Pharmacokinetics and Toxicity in Cancer Patients

RATIONALE: 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.

PURPOSE: Phase I trial to study genetic testing and the effectiveness of irinotecan in treating patients who have solid tumors and lymphoma.

OBJECTIVES:

  • 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.
  • Identify UGT1A1 enzyme glucuronidator and irinotecan oxidizer phenotypes in these patients and determine the correlation between the two metabolic reactions in vivo.
  • 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.
  • 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.

PROJECTED ACCRUAL: A total of 30-60 patients will be accrued for this study within 20 months.

Phase I
Interventional
Treatment
  • Lymphoma
  • Small Intestine Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Drug: irinotecan hydrochloride
  • Genetic: mutation analysis
 
 

*   Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
 
Completed
 
 
 

DISEASE CHARACTERISTICS:

  • Histologically proven solid tumor or lymphoma

    • Responded to irinotecan OR no existing curative therapy
  • No leukemia
  • Measurable or evaluable disease

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • Karnofsky 70-100%

Life expectancy:

  • Not specified

Hematopoietic:

  • WBC at least 3500/mm^3
  • Absolute neutrophil count at least 1500/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic:

  • Bilirubin normal
  • SGOT/SGPT less than 5 times upper limit of normal (unless due to disease)

Renal:

  • Creatinine no greater than 1.5 mg/dL OR
  • Creatinine clearance at least 60 mL/min

Other:

  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No inflammatory bowel disease requiring therapy
  • No chronic diarrhea syndrome or paralytic ileus

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • At least 2 weeks since prior colony stimulating factor
  • At least 4 weeks since prior biologic therapy
  • No concurrent biologic therapy

Chemotherapy:

  • See Disease Characteristics
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
  • No other concurrent chemotherapy

Endocrine therapy:

  • Not specified

Radiotherapy:

  • At least 4 weeks since prior radiotherapy to greater than 25% of bone marrow
  • No concurrent palliative radiotherapy

Surgery:

  • No prior transplant

Other:

  • No concurrent substrates of UGT1A1 enzyme
  • No concurrent inducers or inhibitors of UGT1A1 enzyme activity
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00003970
 
CDR0000067173, UCCRC-T98-0039, UCCRC-L97-0270, NCI-T98-0039
University of Chicago
National Cancer Institute (NCI)
Study Chair: Mark J. Ratain, MD University of Chicago
National Cancer Institute (NCI)
October 2003

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP