Clinical trial NCT00731276: Irinotecan in Treating Asian Patients With Solid Tumors
Official title: Phase I Study to Investigate Genotype-based Dose Individualization of Irinotecan in Asian Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Unspecified Adult Solid Tumor, Protocol Specific
Keywords: unspecified adult solid tumor, protocol specific
Lead sponsor: National Cancer Centre, Singapore
Sponsor class: OTHER
First posted: 2008-08-08
Enrollment: 18
Sex: ALL
Minimum age (years): 21
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility 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

Primary outcomes:
measure: Dose-limiting toxicity
timeFrame: No time frame defined. Trial is still recruiting.
measure: Maximum tolerated dose
timeFrame: No time frame defined. Trial is still recruiting.
Secondary outcomes:
measure: Pharmacokinetics
timeFrame: No time frame defined. Trial is still recruiting.
measure: Time to tumor response
timeFrame: No time frame defined. Trial is still recruiting.
measure: Time to progression
timeFrame: No time frame defined. Trial is still recruiting.
measure: Response duration
timeFrame: No time frame defined. Trial is still recruiting.
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: National Cancer Centre - Singapore
Study officials:
affiliation: National Cancer Centre, Singapore
name: Su Pin Choo, MD
role: PRINCIPAL_INVESTIGATOR
References: