Irinotecan in Treating Asian Patients With Solid Tumors

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. PURPOSE: This phase I trial is studying the side effects and best dose of irinotecan in treating Asian patients with solid tumors.

Detailed Description
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OBJECTIVES: Primary To determine the dose-limiting toxicity and maximum tolerated dose of irinotecan hydrochloride according to the genotype status of Asian patients with solid tumors. Secondary To investigate the pharmacokinetics of irinotecan hydrochloride and its metabolites SN-38 and SN-38G. To evaluate time to tumor response, response duration, and time to progression in these patients. OUTLINE: Patients are stratified according to genotype status (UGT1A1*28 vs UGT1A1*6) Patients receive irinotecan hydrochloride IV once weekly for 3 weeks. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection periodically for pharmacogenetic, pharmacokinetic, and pharmacodynamic studies.

Official Title
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Phase I Study to Investigate Genotype-based Dose Individualization of Irinotecan in Asian Cancer Patients

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: irinotecan hydrochloride
* Other: pharmacogenomic studies
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed solid tumors Failed at least one line of prior chemotherapy Must belong to either Chinese, Malay, or Indian ethnic groups Previously irradiated disease allowed provided marker lesions not within the irradiated field Presence of at least one bidimensionally measurable, non-CNS indicator lesion, defined by radiologic study (including CT or MRI scan, ultrasound, or chest X-ray) or physical exam, meeting 1 of the following criteria: Measurable disease on CT or MRI scan must have one diameter ≥ 1 cm and one diameter ≥ 2 cm Measurable disease on chest X-ray or ultrasound must have both diameters ≥ 2 cm Palpable tumor masses that cannot be evaluated radiologically must have two diameters ≥ 2 cm Measurable skin lesion must have at least one diameter ≥ 1 cm No unidimensionally measurable or evaluable only disease No known brain or leptomeningeal metastasis No uncontrolled large pleural effusions PATIENT CHARACTERISTICS: ECOG performance status 0-2 Life expectancy ≥ 3 months Absolute granulocyte count ≥ 1,000/µL WBC ≥ 3,500/µL Hemoglobin ≥ 9 g/dL Platelet count ≥ 100,000/µL Serum total bilirubin ≤ 2.0 mg/dL ALT/AST < 2.5 times normal (5 times normal in patients with known metastatic disease in the liver) Creatinine clearance ≥ 60 mL/min Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No medical problems severe enough to prevent compliance with the study requirements No prior malignancies, except for adequately treated basal cell or squamous cell carcinoma, carcinoma in situ of the cervix, or other cancer for which the patient has been disease-free for 5 years No active or uncontrolled infection No pre-existing cardiac disease, including congestive heart failure, arrhythmia requiring treatment, or myocardial infarction within the past 3 months No pneumonitis No uncontrolled diabetes mellitus (i.e., random blood glucose > 200 mg/dL) No inflammatory bowel disease PRIOR CONCURRENT THERAPY: At least 1 week since prior and no concurrent ketoconazole More than 4 weeks since prior chemotherapy or radiotherapy At least 2 weeks since prior and no concurrent Hypericum perforatum (St. John wort) No prior irinotecan hydrochloride No concurrent investigational antineoplastic therapy or other investigational drugs

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Four Regimens<br>The study has four type of regimens, and dosing of irinotecan depends on genotype of patient. Four Regimens are: Weekly Irinotecan (Irinotecan given at day 1, 8 and 15) every four weekly Weekly Xeliri ( Irinotecan given at day 1, 8 and 15)+ (Xeloda tabs 2000mg/m2 consumed over 14 days) every three weekly Three-weekly Xeliri (Irinotecan given at day 1 only) + (Xeloda tabs 2000mg/m2 consumed over 14 days) every three weekly Two-weekly FOLFIRI (Irinotecan given at day 1 only) + (CI Fluorouracil 600mg/m2 over 22hrs, IV Folinic Acid 200mg/m2 over 2hrs and IVP Fluorouracil 400mg/m2) every two weekly | Drug: irinotecan hydrochloride<br> <br> Other: pharmacogenomic studies<br> <br> Other: pharmacological study<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity |  | No time frame defined. Trial is still recruiting. | 
| Maximum tolerated dose |  | No time frame defined. Trial is still recruiting. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics |  | No time frame defined. Trial is still recruiting. | 
| Time to tumor response |  | No time frame defined. Trial is still recruiting. | 
| Time to progression |  | No time frame defined. Trial is still recruiting. | 
| Response duration |  | No time frame defined. Trial is still recruiting. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific