A Phase I Study Of CEP-701 In Patients With Refractory Neuroblastoma (IND # 67,722)

Fecha de inicio: 1 de agosto de 2003

DISEASE CHARACTERISTICS: * Diagnosis of neuroblastoma confirmed by at least 1 of the following: * Histology * Demonstrates clumps of tumor cells in the bone marrow with elevated urinary catecholamine metabolites * Recurrent or resistant/refractory disease * Neuroblastoma metastatic to the bone marrow with granulocytopenia, anemia, and/or thrombocytopenia allowed * High-risk disease * Patients in first response after completion of a prior front-line myeloablative regimen OR who were medically ineligible to receive a front-line myeloablative regimen must meet at least 1 of the following criteria: * Viable neuroblastoma determined by biopsy of a persistent lesion as seen on CT scan, MRI, or metaiodobenzylguanidine (MIBG) scan * If lesion was irradiated, biopsy must be performed at least 4 weeks after completion of prior radiotherapy * Morphologic evidence of tumor in bone marrow * Second or greater response (without histologic confirmation) allowed * Meets at least 1 of the following criteria: * At least 1 unidimensionally measurable lesion on CT scan, MRI, or X-ray * At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan * MIBG scan with positive uptake at a minimum of 1 site * Bone marrow with tumor cells on routine morphology (not by NSE staining only) of bilateral aspirate and/or biopsy AND/OR at least 5 tumor cells/10\^6 mononuclear cells in the bone marrow by immunocytologic analysis of 2 consecutive bone marrows performed at least 1 day but no more than 4 weeks apart PATIENT CHARACTERISTICS: Age * 21 and under at diagnosis Performance status * Karnofsky 50-100% (for patients \> 16 years of age) * Lansky 50-100% (for patients ≤ 16 years of age) Life expectancy * More than 2 months Hematopoietic * See Disease Characteristics * Absolute neutrophil count ≥ 1,000/mm\^3 * Platelet count ≥ 50,000/mm\^3 (transfusion independent) * Hemoglobin ≥ 8.0 g/dL (red blood cell transfusions allowed) Hepatic * ALT and AST ≤ 3.0 times upper limit of normal (ULN) * Total bilirubin ≤ 1.5 times ULN Renal * Creatinine ≤ 1.5 times normal OR * Creatinine clearance or radioisotope glomerular filtration rate ≥ 60 mL/min Cardiovascular * Ejection fraction ≥ 50% by echocardiogram or MUGA OR * Fractional shortening ≥ 28% or above lower limit of normal by echocardiogram Pulmonary * Lung function normal * No dyspnea at rest * No exercise intolerance * No supplemental oxygen requirement Other * Not pregnant * Negative pregnancy test * Fertile patients must use effective contraception * No uncontrolled infection * No other concurrent illness that would preclude study treatment PRIOR CONCURRENT THERAPY: Biologic therapy * See Chemotherapy * At least 2 weeks since prior biologic or non-myelosuppressive therapy and recovered * More than 7 days since prior growth factors * No prior allogeneic stem cell transplantation AND no extensive chronic graft-versus-host disease * No concurrent growth factors except filgrastim (G-CSF) or sargramostim (GM-CSF) administered for neutropenia lasting for more than 7 days or for confirmed or clinical septicemia associated with neutropenia Chemotherapy * At least 3 months since prior myeloablative chemotherapy with stem cell transplantation * At least 2 weeks since prior chemotherapy and recovered Endocrine therapy * No concurrent corticosteroid therapy except replacement therapy for adrenal insufficiency or treatment for increased intracranial pressure Radiotherapy * See Disease Characteristics * Recovered from prior radiotherapy * At least 6 weeks since prior therapeutic-dose MIBG * At least 6 weeks since prior craniospinal or other radiotherapy involving significant bone marrow (i.e., total pelvis or total abdomen) * At least 4 weeks since prior radiotherapy to any site biopsied * At least 2 weeks since prior local palliative radiotherapy (small port) Surgery * Not specified Other * No prior CEP-701 * No concurrent administration of any of the following CYP3A4 inhibitors: * Cyclosporine * Clotrimazole * Ketoconazole * Erythromycin * Clarithromycin * Troleandomycin * HIV protease inhibitors * Nefazodone * Itraconazole * Voriconazole