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

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ClinicalTrials.gov Identifier: NCT02030964
Recruitment Status : Active, not recruiting
First Posted : January 9, 2014
Last Update Posted : September 29, 2022
National Cancer Institute (NCI)
Information provided by (Responsible Party):
New Approaches to Neuroblastoma Therapy Consortium

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.

Condition or disease Intervention/treatment Phase
Neuroblastoma Drug: DFMO Drug: Celecoxib Drug: Cyclophosphamide Drug: Topotecan Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : December 2013
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : June 2023

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02030964

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United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027-0700
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
Canada, Ontario
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Sponsors and Collaborators
New Approaches to Neuroblastoma Therapy Consortium
National Cancer Institute (NCI)
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Study Chair: Michael Hogarty, MD Children's Hospital of Philadelphia
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Responsible Party: New Approaches to Neuroblastoma Therapy Consortium
ClinicalTrials.gov Identifier: NCT02030964    
Other Study ID Numbers: N2012-01
P01CA081403 ( U.S. NIH Grant/Contract )
First Posted: January 9, 2014    Key Record Dates
Last Update Posted: September 29, 2022
Last Verified: September 2022
Additional relevant MeSH terms:
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Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Cyclooxygenase 2 Inhibitors