Fenretinide in Treating Children With Solid Tumors

Study Overview
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Brief Summary
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Phase I trial to study the effectiveness of fenretinide in treating children who have solid tumors that have not responded to standard therapy. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

Detailed Description
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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.

Official Title
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A Phase I Study of Fenretinide (NSC #374551) in Children With High Risk Solid Tumors

Conditions
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Neuroblastoma, Unspecified Childhood Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: fenretinide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>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. | Drug: fenretinide<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent neuroblastoma, unspecified childhood solid tumor, protocol specific