N2012-01: Phase 1 Study of Difluoromethylornithine (DFMO) and Celecoxib With Cyclophosphamide/Topotecan (DFMO)
|ClinicalTrials.gov Identifier: NCT02030964|
Recruitment Status : Active, not recruiting
First Posted : January 9, 2014
Last Update Posted : January 19, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Neuroblastoma||Drug: DFMO Drug: Celecoxib Drug: Cyclophosphamide Drug: Topotecan||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||N2012-01: Phase 1 Study of Difluoromethylornithine (DFMO) and Celecoxib With Cyclophosphamide/Topotecan for Patients With Relapsed or Refractory Neuroblastoma|
|Study Start Date :||December 2013|
|Estimated Primary Completion Date :||May 2018|
|Estimated Study Completion Date :||December 2018|
Experimental: DFMO, Celecoxib, Cyclophosphamide & Topotecan
Reconstituted DFMO powder by mouth for 14 days and celecoxib capsule by mouth daily in each cycle. Cyclophosphamide and Topotecan IV on days 8-12 in cycle 1 and days 1-5 of cycles 2-17. Patients may continue for up to 17 cycles as long as therapy is tolerated (no DLT) and disease progression does not occur (SD or better). *Cycle 1 will include a 7 day lead-in with DFMO and celecoxib to deplete tumor polyamines.
Other Name: DifluoromethylornithineDrug: Celecoxib
Other Name: CelebrexDrug: Cyclophosphamide
Other Name: CytoxanDrug: Topotecan
Other Name: Hycamtin
- Number of participants with adverse events as a measure of safety and tolerability. [ Time Frame: Approximately 1 year ]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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02030964
|United States, California|
|Children's Hospital Los Angeles|
|Los Angeles, California, United States, 90027-0700|
|Lucile Packard Children's Hospital at Stanford University Medical Center|
|Palo Alto, California, United States, 94304|
|UCSF Helen Diller Family Comprehensive Cancer Center|
|San Francisco, California, United States, 94115|
|United States, Colorado|
|Children Hospital of Colorado|
|Aurora, Colorado, United States, 80045|
|United States, Georgia|
|AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus|
|Atlanta, Georgia, United States, 30322|
|United States, Illinois|
|University of Chicago Comer Children's Hospital|
|Chicago, Illinois, United States, 60637|
|United States, Massachusetts|
|Childrens Hospital Boston, Dana-Farber Cancer Institute.|
|Boston, Massachusetts, United States, 02115|
|United States, Michigan|
|C.S Mott Children's Hospital|
|Ann Arbor, Michigan, United States, 48109|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center|
|Cincinnati, Ohio, United States, 45229-3039|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104-4318|
|United States, Texas|
|Cook Children's Medical Center - Fort Worth|
|Fort Worth, Texas, United States, 76104|
|United States, Washington|
|Children's Hospital and Regional Medical Center - Seattle|
|Seattle, Washington, United States, 98105|
|Sydney Childrens Hospital KCC|
|Randwick, Australia, 2031|
|Hospital for Sick Children|
|Toronto, Ontario, Canada, M5G 1X8|
|Study Chair:||Michael Hogarty, MD||Children's Hospital of Philadelphia|