Unspecified Childhood Solid Tumor, Protocol Specific
Conditions
Keywords
unspecified childhood solid tumor, protocol specific
Brief summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase I trial to study the effectiveness of irinotecan in treating children who have refractory or progressive solid tumors.
Detailed description
OBJECTIVES: * Determine the maximum tolerated dose and dose-limiting toxicity of irinotecan in children with refractory or progressive solid tumors. * Determine the pharmacokinetics of this drug and its metabolites (SN-38, SN-38G, and APC) administered with and without concurrent anticonvulsants in this patient population. * Determine the benefit this drug offers this patient population. OUTLINE: This is a dose-escalation, multicenter study. Patients are accrued into stratum 1 initially and into stratum 2 if stratum 1 closes due to dose-limiting toxicity of myelosuppression or diarrhea. Patients on anticonvulsants will be accrued into stratum 3 and must meet the eligibility criteria for the stratum that is open (stratum 1 or stratum 2). (Stratum 1 closed as of 2002-09-15). Patients receive irinotecan IV over 90 minutes weekly for 4 weeks. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of irinotecan until the maximum tolerated dose (MTD) with and without anticonvulsants is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients are followed every 6 months for 4 years and then annually thereafter. PROJECTED ACCRUAL: Approximately 20-25 patients will be accrued for this study.
Interventions
DRUGirinotecan hydrochloride
Sponsors
Texas Children's Cancer Center
Study design
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
1 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed solid tumor refractory to standard therapy or for which no known effective therapy exists * Brain tumors eligible * Histologic verification waived for brain stem gliomas * Evaluable disease * No bone marrow involvement PATIENT CHARACTERISTICS: Age: * 1 to 21 Performance status: * Karnofsky 50-100% (over age 10) * Lansky 50-100% (age 10 and under) Life expectancy: * At least 8 weeks Hematopoietic: * Absolute neutrophil count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 * Hemoglobin at least 8 g/dL Hepatic: * Bilirubin less than 1.5 mg/dL * SGPT less than 5 times normal Renal: * Creatinine normal OR * Glomerular filtration rate at least 70 mL/min Other: * No uncontrolled infection * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 6 months after study PRIOR CONCURRENT THERAPY: Biologic therapy: * At least 6 months since prior autologous bone marrow transplantation (BMT) (not including stem cell rescue after high-dose chemotherapy) * At least 1 week since prior growth factors * No prior BMT with total body irradiation (stratum I) * No prior BMT with or without total body irradiation (stratum 2) * No prior allogeneic BMT (all strata) * No concurrent sargramostim (GM-CSF) * No other concurrent prophylactic growth factor support during the first course of therapy Chemotherapy: * At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) * No prior irinotecan * No more than 2 prior multi-agent chemotherapy regimens (stratum 2) * No other concurrent chemotherapy Endocrine therapy: * Concurrent dexamethasone allowed if on stable or decreasing dose for at least 2 weeks prior to study Radiotherapy: * At least 6 months since prior craniospinal radiotherapy or radiotherapy to 50% or more of the pelvis * At least 6 weeks since other prior substantial bone marrow radiotherapy * No prior central axis radiotherapy, pelvic radiotherapy, and/or total abdominal radiotherapy (stratum 2) Surgery: * Not specified Other: * Recovered from all prior therapy * No other concurrent investigational agents * Concurrent enzyme-inducing anticonvulsants (e.g., phenytoin, phenobarbital, carbamazepine) allowed if on stable dose for at least 2 weeks prior to study (stratum 3) * Concurrent valproic acid allowed if combined with another enzyme inducing anticonvulsant drug (stratum 3)
Countries
United States
Outcome results
None listed