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N2012-01: Phase 1 Study of Difluoromethylornithine (DFMO) and Celecoxib With Cyclophosphamide/Topotecan

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by New Approaches to Neuroblastoma Therapy Consortium
Information provided by (Responsible Party):
New Approaches to Neuroblastoma Therapy Consortium Identifier:
First received: January 2, 2014
Last updated: August 28, 2014
Last verified: August 2014

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 Intervention Phase
Drug: DFMO
Drug: Celecoxib
Drug: Cyclophosphamide
Drug: Topotecan
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: N2012-01: Phase 1 Study of Difluoromethylornithine (DFMO) and Celecoxib With Cyclophosphamide/Topotecan for Patients With Relapsed or Refractory Neuroblastoma

Resource links provided by NLM:

Further study details as provided by New Approaches to Neuroblastoma Therapy Consortium:

Primary Outcome Measures:
  • Number of participants with adverse events as a measure of safety and tolerability. [ Time Frame: Approximately 1 year ] [ Designated as safety issue: Yes ]
    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.

Estimated Enrollment: 30
Study Start Date: December 2013
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: DFMO
Other Name: Difluoromethylornithine
Drug: Celecoxib
Other Name: Celebrex
Drug: Cyclophosphamide
Other Name: Cytoxan
Drug: Topotecan
Other Name: Hycamtin


Ages Eligible for Study:   2 Years to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02030964

Contact: Araz Marchelian, MD 323-361-5867

United States, California
Children's Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027-0700
Contact: Araz Marachelian, MD    323-361-5687   
Lucile Packard Children's Hospital at Stanford University Medical Center Not yet recruiting
Palo Alto, California, United States, 94304
Contact: Clare Twist, MD    650-723-5535      
UCSF Helen Diller Family Comprehensive Cancer Center Not yet recruiting
San Francisco, California, United States, 94115
Contact: Katherine Matthay, MD    415-476-3831   
United States, Colorado
Children Hospital of Colorado Not yet recruiting
Aurora, Colorado, United States, 80045
Contact: Margaret Macy, MD    720-777-8856   
United States, Georgia
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus Not yet recruiting
Atlanta, Georgia, United States, 30322
Contact: Kelly Goldsmith, MD    404-785-0853   
United States, Illinois
University of Chicago Comer Children's Hospital Recruiting
Chicago, Illinois, United States, 60637
Contact: Susan L. Cohn, MD    773-702-2571   
United States, Massachusetts
Childrens Hospital Boston, Dana-Farber Cancer Institute. Not yet recruiting
Boston, Massachusetts, United States, 02115
Contact: Suzanne - Shusterman, MD    617-632-3725   
United States, Michigan
C.S Mott Children's Hospital Not yet recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Gregory Yanik, MD    734-936-8785   
United States, North Carolina
Duke University Medical Center Not yet recruiting
Durham, North Carolina, United States, 27710
Contact: Susan Kreissman, MD    919-684-3401      
Contact: Michael Armstrong, MD    919-668-9055      
United States, Ohio
Cincinnati Children's Hospital Medical Center Not yet recruiting
Cincinnati, Ohio, United States, 45229-3039
Contact: Brian Weiss, MD    513-636-9863   
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104-4318
Contact: Yael Mosse, MD    215-590-0965   
United States, Texas
Cook Children's Medical Center - Fort Worth Recruiting
Fort Worth, Texas, United States, 76104
Contact: Meaghan Granger, MD    682-885-4007   
United States, Washington
Children's Hospital and Regional Medical Center - Seattle Not yet recruiting
Seattle, Washington, United States, 98105
Contact: Julie R. Park, MD    206-987-1947   
Sponsors and Collaborators
New Approaches to Neuroblastoma Therapy Consortium
  More Information

No publications provided

Responsible Party: New Approaches to Neuroblastoma Therapy Consortium Identifier: NCT02030964     History of Changes
Other Study ID Numbers: N2012-01, P01CA081403
Study First Received: January 2, 2014
Last Updated: August 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral
Alkylating Agents
Analgesics, Non-Narcotic
Anti-Infective Agents
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antiparasitic Agents
Antiprotozoal Agents
Antirheumatic Agents
Central Nervous System Agents
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Immunologic Factors processed this record on November 25, 2014