N2004-04: Fenretinide LXS in Treating Patients With Recurrent, Refractory, or Persistent Neuroblastoma
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.
Drug: fenretinide lipid matrix
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of Fenretinide (4-HPR, NSC 374551) Lym-X-Sorb™ (LXS) Oral Powder in Patients With Recurrent or Resistant Neuroblastoma|
- Maximum tolerated dose a [ Designated as safety issue: Yes ]
- Toxicity [ Designated as safety issue: Yes ]
- Plasma pharmacokinetics of 4-HPR/LXS oral powder and its metabolites [ Designated as safety issue: No ]
- Tolerability of the combination of ketoconazole and 4-HPR/LXS oral powder [ Designated as safety issue: No ]
- Disease response [ Designated as safety issue: No ]
- Plasma level of 4-HPR/LXS oral powder in PBMC as a tumor cell surrogate tissue [ Designated as safety issue: No ]
- Plasma levels of 4-HPR/LXS oral powder when given in combination with ketoconazole [ Designated as safety issue: No ]
|Study Start Date:||December 2005|
|Estimated Study Completion Date:||December 2015|
|Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
- Determine the maximum tolerated dose of fenretinide (4-HPR) Lym-X-Sorb™ (LXS) oral powder (4-HPR/LXS oral powder) in patients with recurrent, refractory, or persistent neuroblastoma.
- Define the toxicities of 4-HPR/LXS oral powder in these patients.
- Determine the plasma pharmacokinetics of 4-HPR/LXS oral powder and its metabolites in these patients.
- Determine the tolerability of the combination of ketoconazole and 4-HPR/LXS oral powder in these patients.
- Determine the response rate in patients treated with 4-HPR/LXS oral powder.
- Determine the level of 4-HPR/LXS oral powder in normal peripheral blood mononuclear cells (PBMC) as a tumor cell surrogate tissue.
- Determine plasma levels of 4-HPR/LXS oral powder when given in combination with ketoconazole.
- Determine whether ketoconazole increases 4-HPR/LXS oral powder plasma levels.
OUTLINE: This is a dose-escalation study of fenretinide (4-HPR) Lym-X-Sorb™ (LXS) oral powder, followed by an open-label study. Patients are sequentially assigned to 1 of 2 intervention groups.
- Group I: Patients receive 4-HPR/LXS oral powder 3 times daily on days 0-6.
- Group II: Patients receive 4-HPR/LXS oral powder as in group I and oral ketoconazole once daily on days 0-6.
In both groups, treatment repeats every 21 days for at least 6 courses in the absence of disease progression or unacceptable toxicity. Patients in complete remission at study enrollment may receive up to 12 courses (9 months) of therapy.
Blood samples are collected at baseline and during courses 1, 2, and 6 for pharmacokinetic and correlative studies.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 32 patients will be accrued for the dose-escalation portion and 36 will be accrued for the open-label portion of this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00295919
|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, 94143|
|United States, Georgia|
|AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus|
|Atlanta, Georgia, United States, 30342|
|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, Ohio|
|Cincinnati Children's Hospital Medical Center|
|Cincinnati, Ohio, United States, 45229-3039|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104-4318|
|United States, Texas|
|Cook Children's Medical Center - Fort Worth|
|Fort Worth, Texas, United States, 76104|
|United States, Washington|
|Children's Hospital and Regional Medical Center - Seattle|
|Seattle, Washington, United States, 98105|
|Study Chair:||Barry J. Maurer, MD, PhD||Texas Tech University Health Sciences Center|