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

NCT ID: NCT00646230

Last Updated: 2023-04-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-12-31
• Study Completion Date: 2012-03-31

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.

Detailed Description

OBJECTIVES:

Primary

• To determine the maximum tolerated dose of fenretinide when given as a continuous intravenous infusion in young patients with recurrent and/or resistant neuroblastoma.
• To define the toxicities of this drug in these patients.
• To determine the plasma pharmacokinetics of this drug in these patients.

Secondary

• To determine the response rate in patients treated with this drug.
• To determine the bioavailability of fenretinide in normal peripheral blood mononuclear cells as a surrogate marker for drug bioavailability to tumor tissue.

OUTLINE: This is a multicenter study.

Patients receive fenretinide IV continuously over 120 hours on days 0-4. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Blood samples are collected periodically for pharmacokinetic analysis by high performance liquid chromatography.

After completion of study treatment, patients are followed periodically.

Conditions

Neuroblastoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single arm of CIV infusion of emulsion 4-HPR

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

Group Type: EXPERIMENTAL

fenretinide

Intervention Type: DRUG

high performance liquid chromatography

Intervention Type: OTHER

pharmacological study

Intervention Type: OTHER

Interventions

fenretinide

Intervention Type: DRUG

high performance liquid chromatography

Intervention Type: OTHER

pharmacological study

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 0 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Nant Operations Center

OTHER

Sponsor Role: lead

Responsible Party

Nant Operations Center

NANT Operations Center

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Barry J. Maurer, MD, PhD

Role: STUDY_CHAIR

Texas Tech University Health Sciences Center

Locations

Childrens Hospital Los Angeles

Los Angeles, California, United States

Lucile Packard Children's Hospital at Stanford University Medical Center

Palo Alto, California, United States

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

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

Atlanta, Georgia, United States

University of Chicago Comer Children's Hospital

Chicago, Illinois, United States

Children's Hospital Boston

Boston, Massachusetts, United States

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

Ann Arbor, Michigan, United States

Morgan Stanley Children's Hospital of New York-Presbyterian

New York, New York, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, United States

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

Houston, Texas, United States

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, United States

Hospital for Sick Children

Toronto, Ontario, Canada

Countries

United States; Canada

Other Identifiers

P01CA081403

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N2004-03

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000584267

Identifier Type: -

Identifier Source: org_study_id