RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Ecteinascidin 743 may be an effective treatment for solid tumors. PURPOSE: Phase I trial to study the effectiveness of ecteinascidin 743 in treating children who have refractory solid tumors.
OBJECTIVES: I. Determine the maximum tolerated dose and dose-limiting toxicity of ecteinascidin 743 in pediatric patients with refractory solid tumors. II. Determine the pharmacokinetics of this drug in these patients. III. Determine the antitumor activity of this drug in this patient population. OUTLINE: This is a dose escalation, multicenter study. Patients are stratified according to pretreatment (pretreated vs less heavily pretreated). Patients receive ecteinascidin 743 IV over 3 hours on day 1. Treatment continues every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of ecteinascidin 743 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicities. PROJECTED ACCRUAL: A total of 3-20 patients will be accrued for this study within 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
13
Progression Free Survival
Time frame: Length of study
Dose Limiting Toxicity
To determine the maximum tolerated dose (MTD) of vincristine, when used in combination with irinotecan, and the dose-limiting toxicity (DLT) of this combination; irinotecan will be administered IV over 1 hour x 5 days, q 21 days, with vincristine IVP days 1, 8, 15, 22, 29, every 42 days, to children with refractory solid tumors.
Determine a safe and tolerable dose of vincristine, when administered with irinotecan
To determine a safe and tolerable dose of vincristine, when administered with irinotecan, for future evaluation in phase II clinical trials.
Determine the pharmacokinetics of vincristine and irinotecan
To determine the pharmacokinetics of vincristine and irinotecan (and its active metabolite SN-38) when administered in combination to children with refractory cancer.
Time frame: Length of study
Determine the incidence and severity of other toxicities
To determine the incidence and severity of other toxicities of this combination.
Time frame: Length of study
Seek preliminary evidence of anti-tumor activity of irinotecan plus vincristine
To seek preliminary evidence of anti-tumor activity of irinotecan plus vincristine against recurrent solid tumors.
Time frame: Length of study
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University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
University of California San Diego Cancer Center
La Jolla, California, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
Jonsson Comprehensive Cancer Center, UCLA
Los Angeles, California, United States
Beckman Research Institute, City of Hope
Los Angeles, California, United States
Children's Hospital of Orange County
Orange, California, United States
Lucile Packard Children's Hospital at Stanford
Palo Alto, California, United States
UCSF Cancer Center and Cancer Research Institute
San Francisco, California, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Shands Hospital and Clinics, University of Florida
Gainesville, Florida, United States
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