Irinotecan in Treating Asian Patients With Solid Tumors

National Cancer Centre, Singapore

Status and phase: Completed; Phase 1

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Treatments: Other: pharmacological study; Drug: irinotecan hydrochloride; Other: pharmacogenomic studies

Study type: Interventional

Funder types: Other

Identifiers

NCT00731276

SINGAPORE-NCC0703

CDR0000601207

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 18 patients

Sex: All

Ages: 21 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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18 participants in 1 patient group

Four Regimens

Other group

Description:

The study has four type of regimens, and dosing of irinotecan depends on genotype of patient. Four Regimens are: 1. Weekly Irinotecan (Irinotecan given at day 1, 8 and 15) every four weekly 2. Weekly Xeliri ( Irinotecan given at day 1, 8 and 15)+ (Xeloda tabs 2000mg/m2 consumed over 14 days) every three weekly 3. Three-weekly Xeliri (Irinotecan given at day 1 only) + (Xeloda tabs 2000mg/m2 consumed over 14 days) every three weekly 4. 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

Treatment:

Other: pharmacological study

Drug: irinotecan hydrochloride

Other: pharmacogenomic studies