Phase I Study of Fenretinide (4-HPR, NSC 374551) Lym-X-Sorb™ (LXS) Oral Powder in Patients With Recurrent or Resistant Neuroblastoma
- 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
- 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
- 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
- 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
- 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.
Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose a
Barry J. Maurer, MD, PhD
Texas Tech University Health Sciences Center
|Children's Hospital of Philadelphia||Philadelphia, Pennsylvania 19104|
|University of Wisconsin Paul P. Carbone Comprehensive Cancer Center||Madison, Wisconsin 53792-6164|
|Children's Hospital and Regional Medical Center - Seattle||Seattle, Washington 98105|
|Cook Children's Medical Center - Fort Worth||Fort Worth, Texas 76104|
|Cincinnati Children's Hospital Medical Center||Cincinnati, Ohio 45229-3039|
|Childrens Hospital Los Angeles||Los Angeles, California 90027|
|Lucile Packard Children's Hospital at Stanford University Medical Center||Palo Alto, California 95798|
|UCSF Helen Diller Family Comprehensive Cancer Center||San Francisco, California 94115|
|AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus||Atlanta, Georgia 30342|
|C.S. Mott Children's Hospital at University of Michigan Medical Center||Ann Arbor, Michigan 48109-0286|
|Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center||New York, New York 10032|
|Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital||Houston, Texas 77030-2399|
|University of Chicago Comer Children's Hospital||Chicago, Illinois 60637|
|Children's Hospital Boston||Boston, Massachusetts 02115|
|Hospital for Sick Children||New York, New York 10032|