The purpose of this research study is to evaluate an investigational drug (Tolcapone) alone and in combination with oxaliplatin, for relapsed and refractory neuroblastoma. Tolcapone is approved by the U.S. Food and Drug Administration (FDA) for adults, but is an investigational drug in this study because it has not been approved in pediatrics for this indication. Oxaliplatin, although a drug approved by the FDA for other cancers, is investigational for treatment of neuroblastoma in this study. This study will look at the safety and tolerability of tolcapone in combination with oxaliplatin as well as the tumors response to this study drug.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
5
Tolcapone is an oral agent that will be administered every day of each 21-day cycle during Cycle 1 and in combination with oxaliplatin during cycles 2-5 given IV on Day 1 of each 21-day cycle.
Oxaliplatin will be given starting in Cycle 2 at 100 mg/m2 IV on Day 1 of each 21-day cycle
Arkansas Children's Hospital
Little Rock, Arkansas, United States
Rady Children's Hospital
San Diego, California, United States
Connecticut Children's Hospital
Hartford, Connecticut, United States
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
To determine the safety and tolerability of tolcapone alone and in combination with oxaliplatin at 4 dose levels of tolcapone
Time frame: 2 years
Determine the Overall Response Rate (ORR) of Participants using RECIST criteria
To determine the overall response rate (ORR) by the presence of radiologically assessable disease by cross-sectional imaging and in MIBG or PET scans.
Time frame: 3 years
Determine the Progression Free Survival (PFS) of Participants using days until progression
To evaluate the activity of tolcapone in combination with oxaliplatin in relapsed or refractory neuroblastoma based on: Progression free survival (PFS)
Time frame: 3 years
To evaluate the drug levels and pharmacokinetics (PK) of Tolcapone from blood samples at multiple time points within the first 24 hours on study based on Plasma half-life (t1/2).
Tolcapone plasma concentration-time data will be determined for all subjects enrolled on study.
Time frame: 24 hours
To evaluate the drug levels and pharmacokinetics (PK) of Tolcapone from blood samples at multiple time points within the first 24 hours on study based on Plasma clearance (Cl).
Tolcapone plasma concentration-time data will be determined for all subjects enrolled on study.
Time frame: 24 hours
To evaluate the drug levels and pharmacokinetics (PK) of Tolcapone from blood samples at multiple time points within the first 24 hours on study based on Vd.
Tolcapone plasma concentration-time data will be determined for all subjects enrolled on study.
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Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, United States
Helen DeVos Children's Hospital
Grand Rapids, Michigan, United States
Cardinal Glennon Children's Medical Center
St Louis, Missouri, United States
Levine Children's Hospital
Charlotte, North Carolina, United States
Penn State Milton S. Hershey Medical Center and Children's Hospital
Hershey, Pennsylvania, United States
Medical University of South Carolina
Charleston, South Carolina, United States
Time frame: 24 hours
To evaluate the drug levels and pharmacokinetics (PK) of Tolcapone from blood samples at multiple time points within the first 24 hours on study based on Peak Plasma Concentration (Cmax)
Tolcapone plasma concentration-time data will be determined for all subjects enrolled on study.
Time frame: 24 hours
To evaluate the drug levels and pharmacokinetics (PK) of Tolcapone from blood samples at multiple time points within the first 24 hours on study based on Area Under the Curve (AUC).
Tolcapone plasma concentration-time data will be determined for all subjects enrolled on study.
Time frame: 24 hours