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

NCT00646230 | Completed Phase 1 DMC

• 3 other identifiers: CDR0000584267P01CA081403N2004-03
• Study Type: interventional
• Target: 17
• Locations: 2 countries
• Sites: 13

Brief 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.

Conditions

Neuroblastoma

Keywords

recurrent neuroblastoma

Outcome Measures

Primary Outcomes (3)

• To define the toxicities of intravenous emulsion 4-HPR given on this schedule.

  Adverse events, clinically significant changes in lab results or vitals will be captured throughout the duration of the study.

  Adverse events, clinically significant changes in lab results or vitals will be captured throughout the duration of the study.

• To determine the maximum tolerated dose of intravenous emulsion 4-HPR given as a continuous intravenous infusion (CIV) for five days (120 hours) every three weeks in children with recurrent and/or resistant neuroblastoma.

  Tolerability of drug will be assessed throughout the study.

• To determine the plasma pharmacokinetics of intravenous emulsion 4-HPR given on this schedule.

  Pharmacokinetic Profile of Fenretinide - blood levels to be measured in Cycle #1 D0 Hr0, Hrs 6, 12, 24, 36, 48, 72, 96, 120 and end of infusion, then +2 hrs, +48 hrs post infusion. Cycle #2 D1 Hr0 (pre-infusion), then +48 hrs, at the end of infusion.

Secondary Outcomes (3)

• To determine the response rate to intravenous emulsion 4-HPR in patients with recurrent and/or resistant neuroblastoma within the confines of a Phase I study.

  Disease response will be assessed at baseline, End of Cycle #2, End of Cycle #6 and every 4 weeks thereafter.

• To determine the bioavailability to tumor cells of 4-HPR delivered as an intravenous emulsion in normal peripheral blood mononuclear cells (PBMC) as a tumor cell surrogate tissue.

  Assessed Cycle #1 D0 Hr0, D2, +48hrs after start of infusion and C#2 one time for patients >20kg.

• To describe the results of the five gene Five-gene TaqMan® Low Density Array (TLDA) assay for neuroblastoma tumor cells in the bone marrow done at timepoints when bone marrow response is being evaluated by morphology during this therapy.

  Assessed at the end of Cycle #2 & Cycle #6 and then every 4 cycles therafter.

Study Arms (1)

Single arm of CIV infusion of emulsion 4-HPR

EXPERIMENTAL

Single arm study of continuous intravenous infusion (CIV) of emulsion 4-HPR

Drug: fenretinide; Other: high performance liquid chromatography; Other: pharmacological study

Interventions

fenretinide DRUG

Single arm of CIV infusion of emulsion 4-HPR

high performance liquid chromatography OTHER

Single arm of CIV infusion of emulsion 4-HPR

pharmacological study OTHER

Single arm of CIV infusion of emulsion 4-HPR

Eligibility Criteria

• Age: 0 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• New Approaches to Neuroblastoma Therapy Consortium: lead

Study Sites (13)

Childrens Hospital Los Angeles

Los Angeles, California, 90027-0700, United States

Location

Lucile Packard Children's Hospital at Stanford University Medical Center

Palo Alto, California, 94304, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus

Atlanta, Georgia, 30322, United States

Location

University of Chicago Comer Children's Hospital

Chicago, Illinois, 60637, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

C.S. Mott Children's Hospital at University of Michigan Medical Center

Ann Arbor, Michigan, 48109-0286, United States

Location

Morgan Stanley Children's Hospital of New York-Presbyterian

New York, New York, 10032, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, 76104, United States

Location

Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital

Houston, Texas, 77030-2399, United States

Location

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, 98105, United States

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

MeSH Terms

Conditions

Neuroblastoma

Interventions

Fenretinide; Chromatography, High Pressure Liquid

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Pigments, Biological; Biological Factors; Chromatography, Liquid; Chromatography; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Barry J. Maurer, MD, PhD

  Texas Tech University Health Sciences Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2008
• First Posted: March 28, 2008
• Study Start: December 1, 2006
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: April 14, 2026

Record last verified: 2023-04

Locations

US (12); CA (1)