This study will combine an oral drug called DFMO with celecoxib (also oral) and two IV chemotherapy medicines called cyclophosphamide and topotecan. * To find the highest dose of DFMO that can be given with celecoxib, cyclophosphamide and topotecan without causing severe side effects. * To find out the side effects seen by giving DFMO at different dose levels with celecoxib, cyclophosphamide and topotecan. * To measure the levels of DFMO in the blood at different dose levels. * To determine if your tumor gets smaller after treatment with DFMO, celecoxib, cyclophosphamide and topotecan. * To determine if specific gene changes in you or your tumor makes you more prone to side effects or affects your tumor's response to the combination of DFMO, celecoxib, cyclophosphamide and topotecan. * To determine if the amount of normal chemicals in your body called polyamines go down in response to DFMO, celecoxib, cyclophosphamide and topotecan, and whether you are more likely to have a good response to the treatment if they do.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Children's Hospital Los Angeles
Los Angeles, California, United States
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States
Children Hospital of Colorado
Aurora, Colorado, United States
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
Atlanta, Georgia, United States
University of Chicago Comer Children's Hospital
Chicago, Illinois, United States
Childrens Hospital Boston, Dana-Farber Cancer Institute.
Boston, Massachusetts, United States
C.S Mott Children's Hospital
Ann Arbor, Michigan, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Cook Children's Medical Center - Fort Worth
Fort Worth, Texas, United States
...and 3 more locations
Number of participants with adverse events as a measure of safety and tolerability.
The standard 3+3 design for dose escalation will be utilized. 3-6 patients will enroll at each of 4 dose levels, but enrollment to a dosing cohort will cease after observation of DLTs in 2 or more patients. A minimum of 2 to a maximum of 24 patients will be enrolled assuming all 4 dose levels require 6 patients before an MTD is determined. A total of 12 patients may be enrolled at the study defined MTD (including those used to define the MTD) to provide additional adverse event data for safety evaluation.
Time frame: Approximately 1 year
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