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

Primary Purpose

AIDS-related Peripheral/Systemic Lymphoma, AIDS-related Primary CNS Lymphoma, Anaplastic Large Cell Lymphoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
irinotecan hydrochloride
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for AIDS-related Peripheral/Systemic Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Chicago Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (irinotecan hydrochloride)

Arm Description

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.

Outcomes

Primary Outcome Measures

Grade 3-4 diarrhea
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
A chi-squared test will be used to determine whether genotype and phenotype are independent.
Phenotype
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.

Full Information

First Posted
November 1, 1999
Last Updated
January 23, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00003970
Brief Title
Genetic Testing Plus Irinotecan in Treating Patients With Solid Tumors or Lymphoma
Official Title
A Phase I Clinical Trial to Investigate the Correlation Between UGT1A1 Genotype and Irinotecan (CPT-11) Pharmacokinetics and Toxicity in Cancer Patients
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
January 1999 (undefined)
Primary Completion Date
October 2003 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (irinotecan hydrochloride)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
irinotecan hydrochloride
Other Intervention Name(s)
Campto, Camptosar, CPT-11, irinotecan, U-101440E
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Grade 3-4 diarrhea
Description
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.
Time Frame
Up to 4 years
Secondary Outcome Measure Information:
Title
Genotype
Description
A chi-squared test will be used to determine whether genotype and phenotype are independent.
Time Frame
Up to 4 years
Title
Phenotype
Description
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.
Time Frame
Up to 4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Ratain
Organizational Affiliation
University of Chicago Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Chicago Comprehensive Cancer Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637-1470
Country
United States

12. IPD Sharing Statement

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

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