irinotecan in treating children with refractory or advanced solid tumors who are receiving anticonvulsants

Conditions: Unspecified Childhood Solid Tumor, Protocol Specific

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 with refractory or advanced solid tumors who are receiving anticonvulsants.

objectives: * determine the maximum tolerated dose of irinotecan in children with refractory or advanced solid tumors receiving anticonvulsants. * determine the dose-limiting toxicity of irinotecan in this patient population. * evaluate the pharmacokinetic behavior of this treatment regimen in these patients. * determine, preliminarily, the antitumor activity of this treatment regimen in these patients. outline: this is a dose-escalation, multicenter study. patients are stratified according to type of concurrent anticonvulsant (enzyme activating anticonvulsants vs valproic acid vs other anticonvulsants). patients receive irinotecan iv over 1 hour daily for 5 days. treatment repeats every 21 days 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) is reached. the mtd is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. patients are followed every 6 months for up to 4 years and then annually thereafter. projected accrual: a total of 3-25 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically confirmed malignancy refractory to conventional therapy or for which no conventional therapy exists * histologic confirmation not required for brain stem tumors * concurrently on anticonvulsants at a steady level for at least 2 weeks patient characteristics: age: * 1-21 years old performance status: * karnofsky 50-100% (over 10 years of age) * lansky 50-100% (10 years of age or under) life expectancy: * at least 8 weeks hematopoietic: * neutrophil count at least 1,000/mm3 * platelet count at least 100,000/mm3 (transfusion independent) * hemoglobin at least 8.0 g/dl (red blood cell transfusions allowed) hepatic: * bilirubin no greater than 1.5 times normal for age * sgpt less than 5 times normal for age * albumin at least 2 g/dl renal: * creatinine no greater than 1.5 times normal for age or * creatinine clearance or radioisotope glomerular filtration rate at least lower limit of normal for age other: * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no uncontrolled infection * no evidence of active graft-vs-host disease * neurologic deficits for cns tumors stable for at least 2 weeks prior to study prior concurrent therapy: biologic therapy: * at least 1 week since prior antineoplastic biologic therapy * at least 6 months since prior allogeneic stem cell transplantation * at least 1 week since prior growth factors * no concurrent sargramostim (gm-csf) * no concurrent prophylactic growth factors during first course of study therapy * recovered from prior immunotherapy chemotherapy: * at least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosourea) and recovered endocrine therapy: * concurrent dexamethasone for cns tumors with increased intracranial pressure allowed if dose stable or decreasing for at least 2 weeks prior to study radiotherapy: * at least 2 weeks since prior local palliative radiotherapy (small part) * at least 6 months since prior craniospinal radiotherapy * at least 6 months since prior radiotherapy to at least 50% of pelvis * at least 6 weeks since prior substantial bone marrow radiotherapy * recovered from prior radiotherapy surgery: * not specified other: * no other concurrent investigational agent

Keywords: unspecified childhood solid tumor, protocol specific