Irinotecan in Treating Asian Patients With Solid Tumors

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

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.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Other: pharmacological study; Drug: irinotecan hydrochloride; Other: pharmacogenomic studies

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 169610
    • National Cancer Centre - Singapore

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Four Regimens; 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

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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.

Collaborators and Investigators

• Sponsor: National Cancer Centre, Singapore
• Investigators: Principal Investigator: Su Pin Choo, MD, National Cancer Centre, Singapore

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2008
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: August 7, 2008
• First Submitted That Met QC Criteria: August 7, 2008
• First Posted (Estimate): August 8, 2008

Study Record Updates

• Last Update Posted (Actual): March 31, 2017
• Last Update Submitted That Met QC Criteria: March 29, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: CDR0000601207; SINGAPORE-NCC0703

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO