N2004-04: Fenretinide LXS in Treating Patients With Recurrent, Refractory, or Persistent Neuroblastoma

Status: Recruiting
Phase: Phase 1
Diagnosis: Pediatric Neuroblastoma
NCT ID: NCT00295919 (View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 05-302


RATIONALE: Drugs used in chemotherapy, such as fenretinide LXS, 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 fenretinide LXS in treating patients with recurrent, refractory, or persistent neuroblastoma.


Conducting Institutions:
Children's Hospital Boston, Dana-Farber Cancer Institute

Overall PI:
Suzanne Shusterman, MD, Dana-Farber Cancer Institute

Site-responsible Investigators:

Dana-Farber Cancer Institute: Childrens Hospital Pediatric Clinical Translation Investigation Program CTIP, ctip@partners.org

Eligibility Criteria

DISEASE CHARACTERISTICS: - Diagnosis of neuroblastoma either by histology and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines - High-risk disease, as evidenced by ≥ 1 of the following: - Recurrent/progressive disease at any time - Refractory disease (i.e., less than a partial response to frontline therapy) - No biopsy required - Persistent disease after at least a partial response to frontline therapy (i.e., patient has had at least a partial response to frontline therapy but still has residual disease by MIBG scan, CT scan/MRI, or bone marrow) - Biopsy of at least one residual site demonstrating viable neuroblastoma required - Must have ≥ 1 of the following sites of disease: - Measurable tumor, defined as ≥ 2 cm by conventional methods OR ≥ 1 cm by spiral CT - MIBG scan with positive uptake at ≥ 1 site - Tumor cells on routine morphology (not by neuron-specific enolase staining only) of bilateral bone marrow aspirate and/or biopsy on one bone marrow sample - No parenchymal or extradural CNS lesions - Skull lesions with no intracranial soft tissue extension allowed - History of complete surgical resection of CNS lesions allowed if no evidence of CNS lesions at study entry - Prior CNS irradiation allowed PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Life expectancy ≥ 2 months - Hemoglobin ≥ 8.0 g/dL (transfusion independent [i.e., ≥ 2 weeks since last transfusion]) - Absolute neutrophil count ≥ 750/mm^3 (at least 7 days after last dose of growth factor) - Platelet count ≥ 75,000/mm^3 (transfusion independent [ i.e., ≥ 2 weeks since last platelet transfusion]) - Creatinine ≤ 1.5 times normal for age as follows: - No greater than 0.8 mg/dL (for patients 5 years of age and under) - No greater than 1.0 mg/dL (for patients 6-10 years of age) - No greater than 1.2 mg/dL (for patients 11-15 years of age) - No greater than 1.5 mg/dL (for patients over 15 years of age) - Ejection fraction ≥ 55% by echocardiogram or MUGA OR fractional shortening ≥ 27% by echocardiogram - No EKG abnormality severe enough to justify cardiac medications - Bilirubin ≤ 1.5 times normal - ALT and AST ≤ 3 times normal - Seizure disorder allowed provided seizures controlled on anticonvulsants that are not contraindicated - Normal lung function as manifested by no dyspnea at rest, exercise intolerance, or oxygen requirement - Fertile patients must use 2 methods of effective contraception during and for 2 months after completion of study treatment - Not pregnant or nursing - Negative pregnancy test - No skin toxicity > grade 1 - Triglycerides < 300 mg/dL - Calcium < 11.6 mg/dL - No hematuria and/or proteinuria > +1 on urinalysis - No known allergy to soy products - No known severe allergy or sensitivity to wheat gluten PRIOR CONCURRENT THERAPY: - No prior organ transplantation - Fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy - No myelosuppressive chemotherapy and/or biologics within the past 3 weeks (4 weeks for nitrosourea) - No radiotherapy within the past 2 weeks to the site of biopsied lesion or the only site of measurable disease - At least 6 weeks since prior large-field radiotherapy (e.g., total body irradiation, craniospinal therapy, or radiotherapy to the whole abdomen, total lung, or more than 50% marrow space) - At least 3 months since prior autologous stem cell transplantation - No prior allogeneic stem cell transplantation - At least 6 weeks since prior therapeutic MIBG - No hematopoietic growth factors within the past 7 days - No prior fenretinide (other retinoids allowed) - No concurrent antiarrhythmia medications - No other concurrent anticancer agents, including chemotherapy - No concurrent immunomodulatory agents, including systemic corticosteroids - Palliative radiotherapy allowed only to sites not used to measure response - No supplemental vitamin A, E, or ascorbic acid (vitamin C) except as contained in routine total parenteral nutrition vitamin supplements or in a single daily standard-dose oral multivitamin supplement - No concurrent drugs suspected of causing pseudotumor cerebri, including tetracycline, nalidixic acid, nitrofurantoin, phenytoin, sulfonamides, lithium, amiodarone, or vitamin A (except as routine multivitamin supplement) - No concurrent herbal supplements or other alternative therapy medications - No concurrent medications that may potentially act as modulators of intracellular ceramide levels or ceramide cytotoxicity, sphingolipid transport, or p-glycoprotein (MDR1) or MRP1 drug/lipid transporters, including cyclosporine or analogue, verapamil, tamoxifen or analogue, ketoconazole, chlorpromazine, mifepristone, indomethacin, or sulfinpyrazone - No corticosteroids for emesis control - Systemic corticosteroids for asthma control allowed if minimized - Inhaled corticosteroids for asthma control and steroids for routine metabolic deficiency states allowed
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