NeuroblastomaPhase 1DFMONCT02030964
N2012-01: Phase 1 Study of Difluoromethylornithine (DFMO) and Celecoxib With Cyclophosphamide/Topotecan
A Phase 1 study testing DFMO, Celecoxib and Cyclophosphamide in people with Neuroblastoma, run by New Approaches to Neuroblastoma Therapy Consortium at 13 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 30 years
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- DFMO, Celecoxib and Cyclophosphamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 13 sitesin 3 countries
- Study dates
- 16 Jan 2014to 30 Dec 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
13 sites in 3 countries.
13 sites in 3 countries
United States11 sites
C.S Mott Children's Hospital
Ann Arbor, Michigan, 48109
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
Atlanta, Georgia, 30322
Children Hospital of Colorado
Aurora, Colorado, 80045
Childrens Hospital Boston, Dana-Farber Cancer Institute.
Boston, Massachusetts, 02115
University of Chicago Comer Children's Hospital
Chicago, Illinois, 60637
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229-3039
Cook Children's Medical Center - Fort Worth
Fort Worth, Texas, 76104
Children's Hospital Los Angeles
Los Angeles, California, 90027-0700
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104-4318
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94115
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, 98105
About this study
Official title: 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.
- Conditions
- Neuroblastoma
- Being tested
- DFMO, Celecoxib, Cyclophosphamide, Topotecan
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DFMODrug
Also called Difluoromethylornithine
CelecoxibDrug
Also called Celebrex
CyclophosphamideDrug
Also called Cytoxan
TopotecanDrug
Also called Hycamtin
| Study group | Role | What they receive |
|---|---|---|
| DFMO, Celecoxib, Cyclophosphamide & Topotecan | Experimental | 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. Receives: Drug: DFMO; Drug: Celecoxib; Drug: Cyclophosphamide; Drug: Topotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with adverse events as a measure of safety and tolerability.
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.
Measured: Approximately 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2014 (estimated)
- Study start16 Jan 2014
- Primary completion30 Dec 2023
- Study completion30 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeuroblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- New Approaches to Neuroblastoma Therapy Consortium
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Michael Hogarty, MD, Study chair, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02030964
- Sponsor's protocol ID
- N2012-01
- Other IDs
- P01CA081403
- Acronym
- DFMO
- Status last verified
- Feb 2025
- First submitted
- 2 Jan 2014
- Last updated
- 17 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- N2012-01: Phase 1 Study of Difluoromethylornithine (DFMO) and Celecoxib With Cyclophosphamide/Topotecan for Patients With Relapsed or Refractory Neuroblastoma
- ClinicalTrials.gov ID
- NCT02030964
- Acronym / sponsor ID
- DFMO / N2012-01
- Conditions
- Neuroblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- New Approaches to Neuroblastoma Therapy ConsortiumUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 16 Jan 2014 (actual)
- Primary completion
- 30 Dec 2023 (actual)
- Study completion
- 30 Dec 2023 (actual)
- First posted
- 9 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DFMO, Celecoxib, Cyclophosphamide & Topotecan | Experimental | Drug: DFMO, Drug: Celecoxib, Drug: Cyclophosphamide, Drug: TopotecanReconstituted 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. |
Who may qualify
- Ages
- 2 to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DFMOAlso: Difluoromethylornithine | Drug | DFMO, Celecoxib, Cyclophosphamide & Topotecan |
| CelecoxibAlso: Celebrex | Drug | DFMO, Celecoxib, Cyclophosphamide & Topotecan |
| CyclophosphamideAlso: Cytoxan | Drug | DFMO, Celecoxib, Cyclophosphamide & Topotecan |
| TopotecanAlso: Hycamtin | Drug | DFMO, Celecoxib, Cyclophosphamide & Topotecan |
Primary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Hogarty, MD study chair
Children's Hospital of Philadelphia
13 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing DFMO, Celecoxib and Cyclophosphamide in people with Neuroblastoma, run by New Approaches to Neuroblastoma Therapy Consortium at 13 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, Australia, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with adverse events as a measure of safety and tolerability. (time frame: Approximately 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2025.