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Genetic Testing Plus Irinotecan in Treating Patients With Solid Tumors or Lymphoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00003970
First received: November 1, 1999
Last updated: January 23, 2013
Last verified: January 2013
History of Changes
  Purpose

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


Condition Intervention Phase
AIDS-related Peripheral/Systemic Lymphoma
AIDS-related Primary CNS Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Intraocular Lymphoma
Nodal Marginal Zone B-cell Lymphoma
Primary Central Nervous System Non-Hodgkin Lymphoma
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent Small Lymphocytic Lymphoma
Small Intestine Lymphoma
Splenic Marginal Zone Lymphoma
Stage III Adult Burkitt Lymphoma
Stage III Adult Diffuse Large Cell Lymphoma
Stage III Adult Diffuse Mixed Cell Lymphoma
Stage III Adult Diffuse Small Cleaved Cell Lymphoma
Stage III Adult Hodgkin Lymphoma
Stage III Adult Immunoblastic Large Cell Lymphoma
Stage III Adult Lymphoblastic Lymphoma
Stage III Adult T-cell Leukemia/Lymphoma
Stage III Cutaneous T-cell Non-Hodgkin Lymphoma
Stage III Grade 1 Follicular Lymphoma
Stage III Grade 2 Follicular Lymphoma
Stage III Grade 3 Follicular Lymphoma
Stage III Mantle Cell Lymphoma
Stage III Marginal Zone Lymphoma
Stage III Mycosis Fungoides/Sezary Syndrome
Stage III Small Lymphocytic Lymphoma
Stage IV Adult Burkitt Lymphoma
Stage IV Adult Diffuse Large Cell Lymphoma
Stage IV Adult Diffuse Mixed Cell Lymphoma
Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
Stage IV Adult Hodgkin Lymphoma
Stage IV Adult Immunoblastic Large Cell Lymphoma
Stage IV Adult Lymphoblastic Lymphoma
Stage IV Adult T-cell Leukemia/Lymphoma
Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma
Stage IV Grade 1 Follicular Lymphoma
Stage IV Grade 2 Follicular Lymphoma
Stage IV Grade 3 Follicular Lymphoma
Stage IV Mantle Cell Lymphoma
Stage IV Marginal Zone Lymphoma
Stage IV Mycosis Fungoides/Sezary Syndrome
Stage IV Small Lymphocytic Lymphoma
Unspecified Adult Solid Tumor, Protocol Specific
 Drug: irinotecan hydrochloride
 Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Clinical Trial to Investigate the Correlation Between UGT1A1 Genotype and Irinotecan (CPT-11) Pharmacokinetics and Toxicity in Cancer Patients

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Grade 3-4 diarrhea [ Time Frame: Up to 4 years ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Genotype [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    A chi-squared test will be used to determine whether genotype and phenotype are independent.

  • Phenotype [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    A chi-squared test will be used to determine whether genotype and phenotype are independent. Modeled as a function of metabolic ratios and biliary index.


Enrollment: 60
Study Start Date: January 1999
Primary Completion Date: October 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
 Drug: irinotecan hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • CPT-11
  • irinotecan
  • U-101440E

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00003970

Locations
United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637-1470
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Mark Ratain University of Chicago Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00003970     History of Changes
Other Study ID Numbers: NCI-2012-02304, 9531, U01CA069852, CDR0000067173
Study First Received: November 1, 1999
Last Updated: January 23, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
Burkitt Lymphoma
Hodgkin Disease
Immunoblastic Lymphadenopathy
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Mycoses
Mycosis Fungoides
Sezary Syndrome
Lymphoma, B-Cell
 Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Immunoblastic
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Lymphoma, Large-Cell, Anaplastic
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Mantle-Cell
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases

ClinicalTrials.gov processed this record on February 21, 2013