NANT 2012-01: Phase I Study of Difuoromethylornithine (DFMO) and Celecoxib with
Cyclophosphamide/Topotecan for Patients with Relapsed or Refractory Neuroblastoma
What is the purpose of this study?
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
- 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
Who can participate?
- Patients must be > 2 years and < 30 years of age
when registered on study.
- Patients must have recurrent/progressive high-risk neuroblastoma,
refractory high-risk neuroblastoma that had less than a partial response to
standard treatment or persistent high-risk neuroblastoma that had at least a
partial response to standard treatment.
- All patients must have at least ONE site of evaluable
- Patients must have adequate heart, kidney, liver and bone
- Patients who have bone marrow disease must still have
adequate bone marrow function to enter the study.
- Patients with other ongoing serious medical issues must
be approved by the study chair prior to registration.
- Females of childbearing potential that do not have a
negative pregnancy test.
- Patients that are pregnant, breast feeding, or unwilling
to use effective contraception during the study
- Patients status post allogeneic stem cell transplant.
- Patients who, in the opinion of the investigator, may not
be able to comply with the safety monitoring requirements of the study.
- Patients with disease of any major organ system that
would compromise their ability to withstand therapy
- Patients who are on hemodialysis.
- Patients with an active or uncontrolled infection.
Patients on prolonged antifungal therapy are still eligible if they are culture
and biopsy negative in suspected radiographic lesions and meet other organ
- Patients with active bleeding of the GI tract or patients
who have symptoms associated with stomach irritation (known as gastritis).
- Patients who have had a seizure within 12 months prior to
enrollment and patients receiving anti-convulsant therapy for a seizure
- Patients with known Aspirin-Hypersensitivity triad
(asthma, allergic rhinitis, ASA hypersensitivity).
- Patients with known hypersensitivity to celecoxib or
other NSAIDs, aspirin or sulfonamides.
Where can I find additional information?