- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02030964
N2012-01: Phase 1 Study of Difluoromethylornithine (DFMO) and Celecoxib With Cyclophosphamide/Topotecan (DFMO)
February 7, 2024 updated by: New Approaches to Neuroblastoma Therapy Consortium
N2012-01: Phase 1 Study of Difluoromethylornithine (DFMO) and Celecoxib With Cyclophosphamide/Topotecan for Patients With Relapsed or Refractory Neuroblastoma
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.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Estimated)
30
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Randwick, Australia, 2031
- Sydney Childrens Hospital KCC
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Ontario
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Toronto, Ontario, Canada, M5G 1X8
- Hospital for Sick Children
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California
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Los Angeles, California, United States, 90027-0700
- Children's Hospital Los Angeles
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San Francisco, California, United States, 94115
- UCSF Helen Diller Family Comprehensive Cancer Center
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Colorado
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Aurora, Colorado, United States, 80045
- Children Hospital of Colorado
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Georgia
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Atlanta, Georgia, United States, 30322
- AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
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Illinois
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Chicago, Illinois, United States, 60637
- University of Chicago Comer Children's Hospital
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Massachusetts
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Boston, Massachusetts, United States, 02115
- Childrens Hospital Boston, Dana-Farber Cancer Institute.
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Michigan
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Ann Arbor, Michigan, United States, 48109
- C.S Mott Children'S Hospital
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Ohio
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Cincinnati, Ohio, United States, 45229-3039
- Cincinnati Children's Hospital Medical Center
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104-4318
- Children's Hospital of Philadelphia
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Texas
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Fort Worth, Texas, United States, 76104
- Cook Children's Medical Center - Fort Worth
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Washington
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Seattle, Washington, United States, 98105
- Children's Hospital and Regional Medical Center - Seattle
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
7 months to 28 years (Child, Adult)
Accepts Healthy Volunteers
No
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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.
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Other Names:
Other Names:
Other Names:
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of participants with adverse events as a measure of safety and tolerability.
Time Frame: Approximately 1 year
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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.
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Approximately 1 year
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Study Chair: Michael Hogarty, MD, Children's Hospital of Philadelphia
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
January 16, 2014
Primary Completion (Actual)
December 30, 2023
Study Completion (Estimated)
December 30, 2024
Study Registration Dates
First Submitted
January 2, 2014
First Submitted That Met QC Criteria
January 7, 2014
First Posted (Estimated)
January 9, 2014
Study Record Updates
Last Update Posted (Actual)
February 9, 2024
Last Update Submitted That Met QC Criteria
February 7, 2024
Last Verified
February 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Glandular and Epithelial
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroectodermal Tumors, Primitive
- Neuroectodermal Tumors, Primitive, Peripheral
- Neuroblastoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Cyclooxygenase Inhibitors
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Topoisomerase Inhibitors
- Antiprotozoal Agents
- Antiparasitic Agents
- Cyclooxygenase 2 Inhibitors
- Topoisomerase I Inhibitors
- Trypanocidal Agents
- Ornithine Decarboxylase Inhibitors
- Cyclophosphamide
- Celecoxib
- Topotecan
- Eflornithine
Other Study ID Numbers
- N2012-01
- P01CA081403 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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