Fenretinide in Treating Children With Solid Tumors

Neuroblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003191
• Other study ID #: NCI-2012-02262
• Secondary ID: CCG-09709CDR0000
• Status: Completed
• Phase: Phase 1
• First received: November 1, 1999
• Last updated: February 6, 2013
• Start date: March 1998

Study information

• Verified date: August 2006
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. primary completion date: March 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neuroblastoma
• Unspecified Childhood Solid Tumor, Protocol Specific

Intervention

Drug:
• fenretinide

Locations

Country	Name	City	State
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Children's Hospital Medical Center - Cincinnati	Cincinnati	Ohio
United States	Children's Hospital of Columbus	Columbus	Ohio
United States	Cancer Center and Beckman Research Institute, City of Hope	Duarte	California
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Long Beach Memorial Medical Center	Long Beach	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York
United States	Children's Hospital of Orange County	Orange	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Primary Children's Medical Center	Salt Lake City	Utah
United States	UCSF Cancer Center and Cancer Research Institute	San Francisco	California
United States	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia, 

References & Publications (2)

Children's Oncology Group (CCG 09709), Villablanca JG, Krailo MD, Ames MM, Reid JM, Reaman GH, Reynolds CP. Phase I trial of oral fenretinide in children with high-risk solid tumors: a report from the Children's Oncology Group (CCG 09709). J Clin Oncol. 2 — View Citation

Villablanca JG, Ames MW, Reid JM, et al.: Phase I trial of oral [N-(-4-hydroxyphenyl)retinamide] (4-HPR) in children with resistant/recurrent solid tumors: a children's cancer group study (CCG 09709). [Abstract] Proceedings of the American Society of Clin