Fenretinide in Treating Children With Solid Tumors

National Cancer Institute (NCI)

Status and phase: Completed; Phase 1

Conditions: Neuroblastoma; Unspecified Childhood Solid Tumor, Protocol Specific

Treatments: Drug: fenretinide

Study type: Interventional

Funder types: NIH

Identifiers

NCT00003191

CCG-09709

NCI-2012-02262

CDR0000066023 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 18 patients

Sex: All

Ages: Under 21 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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18 participants in 1 patient group

Arm I

Experimental group

Description:

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.

Treatment:

Drug: fenretinide