N2004-03: Intravenous Fenretinide in Treating Young Patients With Recurrent or Resistant Neuroblastoma

• Status: Completed
• Trial end date: 2012-03-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Drugs used in chemotherapy, such as fenretinide, 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 intravenous fenretinide in treating young patients with recurrent or resistant neuroblastoma.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Nant Operations Center
• Collaborator: National Cancer Institute (NCI)
• Treatments: Fenretinide

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of neuroblastoma either by histological confirmation and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines

• Differentiating ganglioneuroblastoma allowed

• No histological evidence only of ganglioneuroma by tumor biopsy or bone marrow biopsy

• High-risk disease meeting at least one of the following criteria:

• Recurrent/progressive disease at any time

• Refractory disease (i.e., less than a partial response to front-line therapy that included ≥ 4 courses of chemotherapy)

• Persistent disease after at least a partial response to front-line therapy (i.e., still has residual disease by MIBG, CT/MRI, or bone marrow biopsy)

• Biopsy of at least one residual site demonstrating viable neuroblastoma required (tumor by bone marrow morphology is considered adequate documentation of disease)

• Measurable disease meeting at least one of the following criteria:

• Measurable tumor on MRI or CT scan, defined as at least one unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan

• For patients with persistent disease, a biopsy* of bone marrow or bone or soft tissue site must have demonstrated viable neuroblastoma

• MIBG scan with positive uptake at a minimum of one site

• For patients with persistent disease, a biopsy* of a MIBG positive site must have demonstrated viable neuroblastoma

• Bone marrow with tumor cells seen on routine morphology (not by NSE staining only) of bilateral aspirate and/or biopsy of one bone marrow sample NOTE: *If the lesion was irradiated, the biopsy must have been done at least 4 weeks after completion of radiotherapy

• No CNS parenchymal or meningeal-based lesions

• Skull-based tumor lesions with or without intracranial extension are allowed provided there are no neurologic signs or symptoms or hydrocephalus related to the lesion

• Patients with a history of complete surgical resection of CNS lesions are eligible provided there is no evidence of CNS lesions by MRI or CT scan at study entry

• Patients with a history of CNS lesions must be off corticosteroid therapy for CNS lesions for ≥ 4 weeks

PATIENT CHARACTERISTICS:

• Performance status 0-2

• Life expectancy ≥ 2 months

• ANC ≥ 500/mm³

• Platelet count ≥ 50,000/mm³ (transfusion independent)

• Hemoglobin ≥ 8.0 g/dL (transfusion independent)

• Serum creatinine ≤ 1.5 times normal for age

• Total bilirubin ≤ 1.5 times normal for age

• ALT and AST ≤ 3 times normal for age

• Serum triglycerides < 300 mg/dL

• Serum calcium < 11.6 mg/dL

• Lipase normal for age

• PT/PTT ≤ 1.5 times upper limit of normal for age (without fresh frozen plasma support; vitamin K allowed)

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception prior to, during, and for 2 months after completion of study treatment

• LVEF ≥ 55% by ECHO or MUGA scan OR fractional shortening ≥ 27% by ECHO

• No EKG abnormality

• No dyspnea at rest or requirement for oxygen

• No hematuria and/or proteinuria > 1+ on urinalysis

• No known history of allergy to egg products

• No known history of allergy to soy bean oil

• No skin toxicity > grade 1 per CTCAE v3

• Seizure disorder allowed if seizures are controlled on anticonvulsants and the anticonvulsant(s) is not contraindicated

• Known genetic, metabolic, or psychiatric conditions, or other ongoing serious medical issues must be approved by the study chair prior to study registration

PRIOR CONCURRENT THERAPY:

• Recovered from all prior chemotherapy, immunotherapy, or radiotherapy

• More than 3 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and/or biologic therapy without stem cell support

• More than 7 days since prior hematopoietic growth factors

• No prior radiotherapy to the only site of measurable disease unless there has been subsequent disease progression at that site or a biopsy of that site showed viable neuroblastoma ≥ 4 weeks after completion of radiotherapy

• Prior CNS irradiation allowed

• At least 2 weeks since prior small field (focal) radiotherapy

• At least 6 weeks since prior large field radiotherapy (i.e., total-body irradiation, craniospinal radiotherapy, whole abdominal or total lung radiotherapy, or radiotherapy to > 50% of marrow space)

• At least 56 days since prior myeloablative autologous stem cell transplantation

• At least 4 weeks since prior myelosuppressive therapy with stem cell support

• At least 6 weeks since prior MIBG therapy

• Prior oral fenretinide therapy allowed

• At least 3 weeks since prior retinoid therapies

• No prior organ transplantation

• No prior myeloablative allogeneic stem cell transplantation unless stem cells were from an identical twin sibling

• No concurrent systemic corticosteroids, including corticosteroids for emesis control

• Concurrent inhaled corticosteroids for asthma control or steroids for metabolic deficiency states allowed

• Concurrent palliative radiotherapy allowed provided the irradiated sites will not be used to measure response

• No concurrent parenteral intralipids

• No other concurrent chemotherapy or immunomodulating agents

• No concurrent drugs suspected of causing pseudotumor cerebri, including tetracycline, nalidixic acid, nitrofurantoin, phenytoin, sulfonamides, lithium, or amiodarone

• No concurrent vitamin A, C, or E supplements (except as part of routine total parenteral nutrition [TPN] supplements or as part of a single daily standard dose of oral multivitamin supplement)

• No concurrent medications that may potentially act as modulators of intracellular ceramide levels or ceramide cytotoxicity, sphingolipid transport, or p-glycoprotein (MDR1) or MDR1 drug/lipid transporters, including cyclosporine or analogue, verapamil, tamoxifen or analogue, ketoconazole, chlorpromazine, mifepristone (RU486), indomethacin, or sulfinpyrazone

• No other concurrent anticancer agents

• No concurrent herbal supplements or other alternative therapy medications

• No concurrent anti-arrhythmia or inotropic cardiac medications