A Phase I Study of Fenretinide (NSC #374551) in Children With High Risk Solid Tumors
N/A
21 Years
Both
Neuroblastoma, Unspecified Childhood Solid Tumor, Protocol Specific
Trial Information
A Phase I Study of Fenretinide (NSC #374551) in Children With High Risk Solid Tumors
OBJECTIVES:
I. Determine the maximum tolerated dose of fenretinide (HPR) in children with high risk
solid tumors.
II. Determine the toxicities of HPR in these patients. III. Determine the pharmacokinetics
of HPR in these patients. IV. Determine the CSF level of HPR in patients whom cerebrospinal
fluid is obtained for routine purposes while on this study.
V. Determine the effect of HPR on plasma retinol levels in these patients. VI. Determine the
activity of HPR in these patients. VII. Determine the antitumor activity of HPR on minimal
residual bone marrow disease in neuroblastoma.
OUTLINE: This is a dose escalation study.
Patients receive oral fenretinide 3 times a day on days 1-7. Treatment repeats every 3 weeks
for up to 8 courses. Patients may receive an additional 22 courses of therapy in the
presence of stable or responding residual tumor. Patients with recurrent neuroblastoma,
after prior myeloablative therapy with no measurable disease, will stop treatment after 8
courses. Cohorts of 3-6 patients receive escalating doses of fenretinide until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2
of 6 patients experience dose limiting toxicity.
Patients are followed until death.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed malignant solid tumor that is refractory to conventional
therapy or recurrent neuroblastoma treated with myeloablative therapy and autologous
stem cell transplant in second complete or partial response
- Bone marrow metastases with granulocytopenia, anemia, and/or thrombocytopenia are
eligible
PATIENT CHARACTERISTICS:
- Age: Under 21 at diagnosis
- Performance status: CCG 0-2
- Life expectancy: At least 2 months
- Absolute neutrophil count at least 750/mm3
- Platelet count at least 50,000/mm3
- Hemoglobin at least 7.0 g/dL
- Bilirubin no greater than 1.5 mg/dL
- SGOT and SGPT less than 2.5 times normal
- Creatinine no greater than 1.5 g/dL OR creatinine clearance at least 50 mL/min OR
radioisotope GFR at least 50 mL/min
- Seizure disorders controlled with anticonvulsants allowed
- No CNS toxicity greater than grade 2
- Not pregnant
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- At least 1 month since prior autologous stem cell transplantation
- No prior allogeneic transplantation
- At least 2 weeks since prior chemotherapy (4 weeks for nitrosourea) and recovered
- No other concurrent chemotherapy
- No concurrent immunomodulating agents (including steroids)
- Concurrent corticosteroid therapy for increased intracranial pressure allowed
- Concurrent dexamethasone for CNS tumor allowed
- At least 2 weeks since prior radiotherapy
- Concurrent radiotherapy to localized lesions allowed
- At least 2 weeks since prior retinoids Prior isotretinoin or 9-cis-retinoic acid
allowed
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Judith G. Villablanca, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Children's Hospital Los Angeles
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-02262
NCT ID:
NCT00003191
Start Date:
March 1998
Completion Date:
Related Keywords:
- Neuroblastoma
- Unspecified Childhood Solid Tumor, Protocol Specific
- recurrent neuroblastoma
- unspecified childhood solid tumor, protocol specific
- Neuroblastoma
- Neoplasms
Name | Location |
|---|---|
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
| University of Texas - MD Anderson Cancer Center | Houston, Texas 77030-4009 |
| University of Michigan Comprehensive Cancer Center | Ann Arbor, Michigan 48109-0752 |
| Children's Hospital of Philadelphia | Philadelphia, Pennsylvania 19104 |
| Mayo Clinic Cancer Center | Rochester, Minnesota 55905 |
| Jonsson Comprehensive Cancer Center, UCLA | Los Angeles, California 90095-1781 |
| Indiana University Cancer Center | Indianapolis, Indiana 46202-5265 |
| University of Minnesota Cancer Center | Minneapolis, Minnesota 55455 |
| UCSF Cancer Center and Cancer Research Institute | San Francisco, California 94115-0128 |
| Vanderbilt-Ingram Cancer Center | Nashville, Tennessee 37232-6838 |
| NYU School of Medicine's Kaplan Comprehensive Cancer Center | New York, New York 10016 |
| University of Wisconsin Comprehensive Cancer Center | Madison, Wisconsin 53792 |
| Cancer Center and Beckman Research Institute, City of Hope | Duarte, California 91010-3000 |
| Herbert Irving Comprehensive Cancer Center | New York, New York 10032 |
| Cancer Institute of New Jersey | New Brunswick, New Jersey 08901 |
| Long Beach Memorial Medical Center | Long Beach, California 90806 |
| Children's Hospital Los Angeles | Los Angeles, California 90027-0700 |
| Children's Hospital of Orange County | Orange, California 92668 |
| Children's National Medical Center | Washington, District of Columbia 20010-2970 |
| Children's Mercy Hospital | Kansas City, Missouri 64108 |
| Children's Hospital Medical Center - Cincinnati | Cincinnati, Ohio 45229-3039 |
| Children's Hospital of Columbus | Columbus, Ohio 43205-2696 |
| Children's Hospital of Pittsburgh | Pittsburgh, Pennsylvania 15213 |
| Children's Hospital and Regional Medical Center - Seattle | Seattle, Washington 98105 |
| Primary Children's Medical Center | Salt Lake City, Utah 84113-1100 |
