Clinical trial NCT02030964: N2012-01: Phase 1 Study of Difluoromethylornithine (DFMO) and Celecoxib With Cyclophosphamide/Topotecan
Official title: N2012-01: Phase 1 Study of Difluoromethylornithine (DFMO) and Celecoxib With Cyclophosphamide/Topotecan for Patients With Relapsed or Refractory Neuroblastoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neuroblastoma
Lead sponsor: New Approaches to Neuroblastoma Therapy Consortium
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2014-01-09
Enrollment: 30
Sex: ALL
Minimum age (years): 2
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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 disease.
* Patients must have adequate heart, kidney, liver and bone marrow function.
* 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.

Exclusion Criteria:

* 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 function criteria.
* 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 disorder.
* Patients with known Aspirin-Hypersensitivity triad (asthma, allergic rhinitis, ASA hypersensitivity).
* Patients with known hypersensitivity to celecoxib or other NSAIDs, aspirin or sulfonamides.

Primary outcomes:
measure: Number of participants with adverse events as a measure of safety and tolerability.
timeFrame: Approximately 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: Children Hospital of Colorado
state: Colorado
city: Atlanta
country: United States
facility: AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Comer Children's Hospital
state: Illinois
city: Boston
country: United States
facility: Childrens Hospital Boston, Dana-Farber Cancer Institute.
state: Massachusetts
city: Ann Arbor
country: United States
facility: C.S Mott Children's Hospital
state: Michigan
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Fort Worth
country: United States
facility: Cook Children's Medical Center - Fort Worth
state: Texas
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center - Seattle
state: Washington
city: Randwick
country: Australia
facility: Sydney Childrens Hospital KCC
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Michael Hogarty, MD
role: STUDY_CHAIR
References: