N2004-03: Intravenous Fenretinide in Treating Young Patients With Recurrent or Resistant Neuroblastoma (IV Fenretinide)
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.
Other: high performance liquid chromatography
Other: pharmacological study
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Intravenous (Emulsion) Fenretinide in Children With Recurrent or Resistant Neuroblastoma|
- To define the toxicities of intravenous emulsion 4-HPR given on this schedule. [ Time Frame: Adverse events, clinically significant changes in lab results or vitals will be captured throughout the duration of the study. ] [ Designated as safety issue: Yes ]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. [ Time Frame: Tolerability of drug will be assessed throughout the study. ] [ Designated as safety issue: No ]
- To determine the plasma pharmacokinetics of intravenous emulsion 4-HPR given on this schedule. [ Time Frame: 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. ] [ Designated as safety issue: No ]
- 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. [ Time Frame: Disease response will be assessed at baseline, End of Cycle #2, End of Cycle #6 and every 4 weeks thereafter. ] [ Designated as safety issue: No ]Response will be measured utilizing any of the following;CT scan, MRI, MIBG scan, Bone Marrow, Urine Catecholamines
- 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. [ Time Frame: Assessed Cycle #1 D0 Hr0, D2, +48hrs after start of infusion and C#2 one time for patients >20kg. ] [ Designated as safety issue: No ]
- 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. [ Time Frame: Assessed at the end of Cycle #2 & Cycle #6 and then every 4 cycles therafter. ] [ Designated as safety issue: No ]
|Study Start Date:||December 2006|
|Estimated Study Completion Date:||December 2014|
|Primary Completion Date:||March 2012 (Final data collection date for primary outcome measure)|
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00646230
|United States, California|
|Childrens Hospital Los Angeles|
|Los Angeles, California, United States, 90027-0700|
|Lucile Packard Children's Hospital at Stanford University Medical Center|
|Palo Alto, California, United States, 94304|
|UCSF Helen Diller Family Comprehensive Cancer Center|
|San Francisco, California, United States, 94115|
|United States, Georgia|
|AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus|
|Atlanta, Georgia, United States, 30322|
|United States, Illinois|
|University of Chicago Comer Children's Hospital|
|Chicago, Illinois, United States, 60637|
|United States, Massachusetts|
|Children's Hospital Boston|
|Boston, Massachusetts, United States, 02115|
|United States, Michigan|
|C.S. Mott Children's Hospital at University of Michigan Medical Center|
|Ann Arbor, Michigan, United States, 48109-0286|
|United States, New York|
|Morgan Stanley Children's Hospital of New York-Presbyterian|
|New York, New York, United States, 10032|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center|
|Cincinnati, Ohio, United States, 45229-3039|
|United States, Texas|
|Cook Children's Medical Center - Fort Worth|
|Fort Worth, Texas, United States, 76104|
|Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital|
|Houston, Texas, United States, 77030-2399|
|United States, Washington|
|Children's Hospital and Regional Medical Center - Seattle|
|Seattle, Washington, United States, 98105|
|Hospital for Sick Children|
|Toronto, Ontario, Canada, M5G 1X8|
|Study Chair:||Barry J. Maurer, MD, PhD||Texas Tech University Health Sciences Center|