The purpose of this study is to find out how safe and effective treatment with a new combination of drugs, vorinostat and etoposide, is in treating cancer. The medication etoposide is a standard medication used in the treatment of cancer in children. Vorinostat is an experimental drug which targets a protein(s) that control the way cancer cells grow and divide. Vorinostat is approved by the FDA in adults with certain cancers but not approved yet in children. There are two parts to this study. In the first part of this study, the phase I portion, a safe dose of the combination, vorinostat and etoposide. The goal of second part of this study, the phase II portion, is to see how effective the combination of vorinostat and etoposide is in treating cancer.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
27
Patients will be assessed in 3-week cycles. Escalating doses of vorinostat will be administered orally on a daily x 4 schedule in combination with a fixed dose of etoposide. Etoposide will be administered intravenously daily x 3 days. Cohorts of 3-6 patients will be treated with vorinostat and etoposide. In the phase II component, patients will be treated at the RP2D established in the Phase I component of the study, which was found to be 270 mg/m2/dose of Vorinostat and 100 mg/m2/dose of Etoposide.
Phoenix Children'S Hospital
Phoenix, Arizona, United States
Children's Hospital Colorado
Aurora, Colorado, United States
Arnold Palmer Hospital for Children/MD Anderson Cancer Center Orlando
Orlando, Florida, United States
All Children's Hospital
St. Petersburg, Florida, United States
John Hopkins Medical Center
Baltimore, Maryland, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Children's Mercy Hospital & Clinics
Kansas City, Missouri, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Pennsylvania State University College of Medicine
Hershey, Pennsylvania, United States
Md Anderson Cancer Center
Houston, Texas, United States
...and 1 more locations
To Establish the Dose Limiting Toxicity (DLT)
of the novel combination vorinostat and etoposide in pediatric patients with refractory solid tumors including tumors of the central nervous system. The Toxicity will be evaluated according to NCI CTCAE Version 4.0.
Time frame: Patients will be assessed in 3-week cycles.
To Establish the Maximum Tolerated Dose (MTD)
of the novel combination vorinostat and etoposide in pediatric patients with refractory solid tumors including tumors of the central nervous system.
Time frame: 1 year
To Establish the Efficacy (CR (Complete Response) + PR (Partial Response) Rate)
of the novel combination vorinostat and etoposide in pediatric patients with relapsed/refractory sarcoma. Evaluation for response will be determined by Revised RECIST guideline
Time frame: 1 year
To Evaluate the Efficacy (CR (Complete Response) + PR (Partial Response) Rate)
of the novel combination vorinostat and etoposide in pediatric patients enrolled in the phase I component of the study. Evaluation for response will be determined by Revised RECIST guideline.
Time frame: 1 year
To Evaluate the Biologic Effects Using Histone Acetylation, Gene Expression Profiling, and Histone Phosphorylation Profiling.
of the novel combination of vorinostat and etoposide in pediatric patients with refractory solid tumors including central nervous system tumors
Time frame: 2 years
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