The purpose of this research study is to evaluate a new investigational drug to prevent reoccurrence of neuroblastoma that is in remission. This study drug is called DFMO. The objectives of this study will be to monitor for safety and look at efficacy of DFMO. The safety of the proposed dosing regimen in this trial will be tested by an on-going risk/benefit assessment during the study. A patient benefiting from treatment, not progressing on therapy, and in the absence of any safety issues associated with DFMO may continue on treatment up to 27 cycles with the expectation that there will be an overall clinical benefit. The procedures involved in this study include Medical history, Physical exam, Vital signs (blood pressure, pulse, temperature), Blood tests, Urine tests, MRI or CT scan of the tumor(s), meta-iodobenzylguanidine (MIBG) scans, and Bone marrow aspirations. All of these tests and procedures are considered standard of care for this population. Drug administration is also part of this protocol, including an investigational new drug called DFMO. The proposed dosing regimen is an oral dose of DFMO tablets two times a day for each day while on study. There will be 27 cycles. Each cycle will be 28 days in length.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
PREVENTION
Masking
NONE
Enrollment
140
Subjects will receive twenty-seven (27) cycles of oral DFMO at a dose of 500 to 1000 mg/m2 BID on each day of a 28 day cycle.
Phoenix Children's Hospital
Phoenix, Arizona, United States
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
Arnold Palmer Hospital for Children
Orlando, Florida, United States
All Children's Hospital Johns Hopkins Medicine
St. Petersburg, Florida, United States
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, United States
Tufts Medical Center
Boston, Massachusetts, United States
Helen DeVos Children's Hospital
Grand Rapids, Michigan, United States
Children's Hospital and Clinics on Minnesota
Minneapolis, Minnesota, United States
...and 12 more locations
Number of Participants With Event Free Survival (EFS) During Study.
To evaluate the preventative activity of DFMO as a single agent in patients that are in remission based on: Event free survival (EFS)
Time frame: 2 Years
Percentage of Participants With Overall Survival (OS)
To evaluate the preventative activity of DFMO as a single agent in patients with neuroblastoma who are in remission based on: Overall Survival (OS)
Time frame: 2 Years
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
To continue to determine the safety and tolerability of DFMO as a single agent and in pediatric and young adult patients with high risk neuroblastoma that is in remission.
Time frame: 2 years
Test the Association of Survival With ODC1 Genotype
Tests (p-value) of the association of survival with ODC1 single nucleotide polymorphism rs2302616 genotype. Blood: microRNA analysis as predictor of DFMO effect, ornithine decarboxylase (ODC) single nucleotide polymorphism (SNP) analysis in DNA isolated from nucleated cells
Time frame: 2 years
Peak Plasma Concentration (Cmax)
Pharmacokinetic assay Cmax/D Samples drawn at 5 timepoints: (0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose) on two different days.
Time frame: Samples drawn at 5 timepoints: (0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose) on two different days
Area Under the Plasma Concentration Versus Time Curve (AUC)
Pharmacokinetic assay AUC(0-6 hr)/D Samples drawn at 5 timepoints: (0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose) on two different days
Time frame: 0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose on two different days
Time to Reach Peak Plasma Concentration (Tmax)
Pharmacokinetic assay- tmax, hr Samples drawn at 5 timepoints: (0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose) on two different days
Time frame: 0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose on two different days
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