Clinical trial NCT00003191: Fenretinide in Treating Children With Solid Tumors
Official title: A Phase I Study of Fenretinide (NSC #374551) in Children With High Risk Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neuroblastoma
Unspecified Childhood Solid Tumor, Protocol Specific
Keywords: recurrent neuroblastoma
unspecified childhood solid tumor, protocol specific
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-11-26
Enrollment: 18
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Duarte
country: United States
facility: Cancer Center and Beckman Research Institute, City of Hope
state: California
city: Long Beach
country: United States
facility: Long Beach Memorial Medical Center
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: San Francisco
country: United States
facility: UCSF Cancer Center and Cancer Research Institute
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey
state: New Jersey
city: New York
country: United States
facility: NYU School of Medicine's Kaplan Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center
state: New York
city: Cincinnati
country: United States
facility: Children's Hospital Medical Center - Cincinnati
state: Ohio
city: Columbus
country: United States
facility: Children's Hospital of Columbus
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Medical Center
state: Utah
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center - Seattle
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Perth
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
Study officials:
affiliation: Children's Hospital Los Angeles
name: Judith G. Villablanca, MD
role: STUDY_CHAIR
References:
citation: 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. 2006 Jul 20;24(21):3423-30. doi: 10.1200/JCO.2005.03.9271.
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 Clinical Oncology 21: A-1588, 2002.