- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00003970
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
Study Overview
Status
Conditions
- Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
- Nodal Marginal Zone B-cell 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 Immunoblastic Large Cell Lymphoma
- Recurrent Adult Lymphoblastic Lymphoma
- Recurrent Grade 1 Follicular Lymphoma
- Recurrent Grade 2 Follicular Lymphoma
- Recurrent Grade 3 Follicular Lymphoma
- Recurrent Mantle Cell Lymphoma
- Recurrent Marginal Zone Lymphoma
- Splenic Marginal Zone Lymphoma
- Unspecified Adult Solid Tumor, Protocol Specific
- Anaplastic Large Cell Lymphoma
- Angioimmunoblastic T-cell Lymphoma
- Intraocular Lymphoma
- Recurrent Adult Hodgkin Lymphoma
- Recurrent Adult T-cell Leukemia/Lymphoma
- Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
- Recurrent Mycosis Fungoides/Sezary Syndrome
- Recurrent Small Lymphocytic Lymphoma
- Small Intestine 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 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 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
- Primary Central Nervous System Non-Hodgkin Lymphoma
- Stage IV Adult Immunoblastic Large Cell Lymphoma
- Stage IV Adult Lymphoblastic Lymphoma
- Stage III Adult Lymphoblastic Lymphoma
- Stage III Adult Immunoblastic Large Cell Lymphoma
- AIDS-related Peripheral/Systemic Lymphoma
- AIDS-related Primary CNS Lymphoma
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Illinois
-
Chicago, Illinois, United States, 60637-1470
- University of Chicago Comprehensive Cancer Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Grade 3-4 diarrhea
Time Frame: 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.
|
Up to 4 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Genotype
Time Frame: Up to 4 years
|
A chi-squared test will be used to determine whether genotype and phenotype are independent.
|
Up to 4 years
|
Phenotype
Time Frame: Up to 4 years
|
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.
|
Up to 4 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Mark Ratain, University of Chicago Comprehensive Cancer Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Virus Diseases
- Infections
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Neoplasms by Site
- Disease Attributes
- Disease
- DNA Virus Infections
- Bacterial Infections and Mycoses
- Tumor Virus Infections
- Leukemia, Lymphoid
- Epstein-Barr Virus Infections
- Herpesviridae Infections
- Leukemia, B-Cell
- Eye Neoplasms
- Lymphadenopathy
- Lymphoma
- Lymphoma, Follicular
- Lymphoma, B-Cell
- Lymphoma, Large B-Cell, Diffuse
- Syndrome
- Leukemia
- Hodgkin Disease
- Recurrence
- Lymphoma, Non-Hodgkin
- Mycoses
- Burkitt Lymphoma
- Lymphoma, Mantle-Cell
- Lymphoma, B-Cell, Marginal Zone
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Lymphoma, Large-Cell, Immunoblastic
- Plasmablastic Lymphoma
- Leukemia, Lymphocytic, Chronic, B-Cell
- Lymphoma, T-Cell
- Lymphoma, T-Cell, Cutaneous
- Leukemia, T-Cell
- Leukemia-Lymphoma, Adult T-Cell
- Mycosis Fungoides
- Sezary Syndrome
- Lymphoma, Large-Cell, Anaplastic
- Intraocular Lymphoma
- Immunoblastic Lymphadenopathy
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Topoisomerase Inhibitors
- Topoisomerase I Inhibitors
- Irinotecan
Other Study ID Numbers
- NCI-2012-02304
- U01CA069852 (U.S. NIH Grant/Contract)
- 9531
- CDR0000067173 (Registry Identifier: PDQ (Physician Data Query))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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