NeuroblastomaPhase 2NCT02395666
Preventative Trial of Difluoromethylornithine (DFMO) in High Risk Patients With Neuroblastoma That is in Remission
A Phase 2 study testing DFMO in people with Neuroblastoma, run by Giselle Sholler at 22 sites in United States.
Trial summary
The purpose of this research study is to evaluate a new investigational drug to prevent reoccurrence of neuroblastoma that is in remission. This study drug is called DFMO. The objectives of this study will be to monitor for safety and look at efficacy of DFMO. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- DFMO
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 22 sitesUnited States
- Study dates
- 5 Mar 2015to 24 Aug 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age: 0-21 years at the time of diagnosis.
- Diagnosis: histologic verification at either the time of original diagnosis or a previous relapse of high risk neuroblastoma.
- Disease Status: Neuroblastoma that is in remission
- First dose of study medication must be greater than 30 days from completion of cytotoxic and antibody therapy and less than 120 days from previous therapy
- A negative serum or urine pregnancy test is required for female subjects of child bearing potential (onset of menses or ≥13 years of age).
- Both male and female post-pubertal study subjects need to agree to use one of the more effective birth control methods during treatment and for six months after treatment is stopped. These methods include total abstinence (no sex), oral contraceptives ("the pill"), an intrauterine device (IUD), levonorgestrel implants (Norplant), or medroxyprogesterone acetate injections (Depo-provera shots). If one of these cannot be used, contraceptive foam with a condom is recommended.
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- Absolute Neutrophil Count (ANC) > 500/μl and platelet count >50,000/μl
- Organ Function Requirements: Subjects must have adequate liver function as defined by:
- Aspartate Aminotransferase (AST) and Alanine transaminase (ALT) <10x upper limit of normal
- Serum bilirubin must be ≤ 2.0 mg/dl
- Serum creatinine based on age/gender
- Informed Consent: All subjects and/or legal guardians must sign informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines
Who cannot join
- Lansky score < 60%
- Body Surface Area (BSA) (m2) of <0.25
- Investigational Drugs: Subjects who are currently receiving another investigational drug are excluded from participation.
- Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are not eligible. Subjects must have fully recovered from the effects of prior chemotherapy (hematological and bone marrow suppression effects).
- Infection: Subjects who have an uncontrolled infection are not eligible until the infection is judged to be well controlled in the opinion of the investigator.
- Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded.
Trial locations and contacts
22 sites in 1 country.
22 sites in 1 country
United States22 sites
Dell Children's Blood and Cancer Center
Austin, Texas, 78723
Tufts Medical Center
Boston, Massachusetts, 02111
Medical University of South Carolina
Charleston, South Carolina, 29425
Levine Children's Hospital
Charlotte, North Carolina, 28204
Nationwide Children's Hospital
Columbus, Ohio, 43205
Children's Medical Center
Dallas, Texas, 75235
Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503
Connecticut Children's Hospital
Hartford, Connecticut, 06106
Penn State Milton S. Hershey Medical Center and Children's Hospital
Hershey, Pennsylvania, 17033
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96813
Texas Children's Cancer and Hematology Centers
Houston, Texas, 77030
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
Arkansas Children's Hospital
Little Rock, Arkansas, 72202
Children's Hospital and Clinics on Minnesota
Minneapolis, Minnesota, 55404
Monroe Carrell Jr. Children's Hospital at Vanderbilt
Nashville, Tennessee, 37232
Arnold Palmer Hospital for Children
Orlando, Florida, 32806
Phoenix Children's Hospital
Phoenix, Arizona, 85016
Primary Children's Hospital
Salt Lake City, Utah, 84113
Rady Children's Hospital
San Diego, California, 92123
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104
All Children's Hospital Johns Hopkins Medicine
St. Petersburg, Florida, 33701
The Children's Hospital at Montefiore
The Bronx, New York, 10467
About this study
Official title: A Phase II Preventative Trial of DFMO (Eflornithine HCl) as a Single Agent in Patients With High Risk Neuroblastoma in Remission
The purpose of this research study is to evaluate a new investigational drug to prevent reoccurrence of neuroblastoma that is in remission. This study drug is called DFMO. The objectives of this study will be to monitor for safety and look at efficacy of DFMO.
The safety of the proposed dosing regimen in this trial will be tested by an on-going risk/benefit assessment during the study. A patient benefiting from treatment, not progressing on therapy, and in the absence of any safety issues associated with DFMO may continue on treatment up to 27 cycles with the expectation that there will be an overall clinical benefit.
Read more
The procedures involved in this study include Medical history, Physical exam, Vital signs (blood pressure, pulse, temperature), Blood tests, Urine tests, MRI or CT scan of the tumor(s), meta-iodobenzylguanidine (MIBG) scans, and Bone marrow aspirations. All of these tests and procedures are considered standard of care for this population. Drug administration is also part of this protocol, including an investigational new drug called DFMO.
The proposed dosing regimen is an oral dose of DFMO tablets two times a day for each day while on study. There will be 27 cycles. Each cycle will be 28 days in length.
- Conditions
- Neuroblastoma
- Being tested
- DFMO
- Keywords
- Neuroblastoma in remission, Relapsed Neuroblastoma, Refractory Neuroblastoma
- 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 eflornithine HCl, Difluoromethylornithine
Subjects will receive twenty-seven (27) cycles of oral DFMO at a dose of 500 to 1000 mg/m2 BID on each day of a 28 day cycle.
| Study group | Role | What they receive |
|---|---|---|
| DFMO twice daily | Experimental | Subjects will receive twenty-seven (27) cycles of oral DFMO at a dose of 500 to 1000 mg/m2 BID on each day of a 28 day cycle. Receives: Drug: DFMO |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Event Free Survival (EFS) During Study.
To evaluate the preventative activity of DFMO as a single agent in patients that are in remission based on: Event free survival (EFS)
Measured: 2 Years
Secondary outcomes (6)
Percentage of Participants With Overall Survival (OS)
To evaluate the preventative activity of DFMO as a single agent in patients with neuroblastoma who are in remission based on: Overall Survival (OS)
Measured: 2 Years
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
To continue to determine the safety and tolerability of DFMO as a single agent and in pediatric and young adult patients with high risk neuroblastoma that is in remission.
Measured: 2 years
Test the Association of Survival With ODC1 Genotype
Tests (p-value) of the association of survival with ODC1 single nucleotide polymorphism rs2302616 genotype.
Blood: microRNA analysis as predictor of DFMO effect, ornithine decarboxylase (ODC) single nucleotide polymorphism (SNP) analysis in DNA isolated from nucleated cells
Measured: 2 years
Peak Plasma Concentration (Cmax)
Pharmacokinetic assay Cmax/D
Samples drawn at 5 timepoints: (0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose) on two different days.
Measured: Samples drawn at 5 timepoints: (0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose) on two different days
Area Under the Plasma Concentration Versus Time Curve (AUC)
Pharmacokinetic assay AUC(0-6 hr)/D
Samples drawn at 5 timepoints: (0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose) on two different days
Measured: 0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose on two different days
Time to Reach Peak Plasma Concentration (Tmax)
Pharmacokinetic assay- tmax, hr
Samples drawn at 5 timepoints: (0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose) on two different days
Measured: 0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose on two different days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2015 (estimated)
- Study start5 Mar 2015
- Primary completion27 Mar 2018
- Study completion24 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- 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 2
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 140 participants (actual)
Sponsor and investigators
- Lead sponsor
- Giselle Sholler
- Sponsor type
- University, hospital or other
- Collaborators
- Beat NB Cancer Foundation, Because of Ezra, K C Pharmaceuticals Inc.
- Responsible party
- Sponsor-investigator, Giselle Sholler, Milton S. Hershey Medical Center
- Investigators
- Giselle Saulnier-Sholler, MD, Study chair, Beat Childhood Cancer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02395666
- Sponsor's protocol ID
- NMTRC003B
- Status last verified
- Aug 2024
- First submitted
- 5 Mar 2015
- Last updated
- 6 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Duke ES, Bradford D, Sinha AK, Mishra-Kalyani PS, Lerro CC, Rivera D, Wearne E, Miller CP, Leighton J, Sabit H, Zhao H, Lane A, Scepura B, Pazdur R, Singh H, Kluetz PG, Donoghue M, Drezner N. US Food and Drug Administration Approval Summary: Eflornithine for High-Risk Neuroblastoma After Prior Multiagent, Multimodality Therapy. J Clin Oncol. 2024 Sep 1;42(25):3047-3057. doi: 10.1200/JCO.24.00546. Epub 2024 Jun 25.
PubMed 38917371Oesterheld J, Ferguson W, Kraveka JM, Bergendahl G, Clinch T, Lorenzi E, Berry D, Wada RK, Isakoff MS, Eslin DE, Brown VI, Roberts W, Zage P, Harrod VL, Mitchell DS, Hanson D, Saulnier Sholler GL. Eflornithine as Postimmunotherapy Maintenance in High-Risk Neuroblastoma: Externally Controlled, Propensity Score-Matched Survival Outcome Comparisons. J Clin Oncol. 2024 Jan 1;42(1):90-102. doi: 10.1200/JCO.22.02875. Epub 2023 Oct 26.
PubMed 37883734Urban-Wojciuk Z, Graham A, Barker K, Kwok C, Sbirkov Y, Howell L, Campbell J, Woster PM, Poon E, Petrie K, Chesler L. The biguanide polyamine analog verlindamycin promotes differentiation in neuroblastoma via induction of antizyme. Cancer Gene Ther. 2022 Jul;29(7):940-950. doi: 10.1038/s41417-021-00386-6. Epub 2021 Sep 14.
PubMed 34522028Batth IS, Dao L, Satelli A, Mitra A, Yi S, Noh H, Li H, Brownlee Z, Zhou S, Bond J, Wang J, Gill J, Sholler GS, Li S. Cell surface vimentin-positive circulating tumor cell-based relapse prediction in a long-term longitudinal study of postremission neuroblastoma patients. Int J Cancer. 2020 Dec 15;147(12):3550-3559. doi: 10.1002/ijc.33140. Epub 2020 Jun 23.
PubMed 32506485Lewis EC, Kraveka JM, Ferguson W, Eslin D, Brown VI, Bergendahl G, Roberts W, Wada RK, Oesterheld J, Mitchell D, Foley J, Zage P, Rawwas J, Rich M, Lorenzi E, Broglio K, Berry D, Saulnier Sholler GL. A subset analysis of a phase II trial evaluating the use of DFMO as maintenance therapy for high-risk neuroblastoma. Int J Cancer. 2020 Dec 1;147(11):3152-3159. doi: 10.1002/ijc.33044. Epub 2020 May 24.
PubMed 32391579
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Preventative Trial of DFMO (Eflornithine HCl) as a Single Agent in Patients With High Risk Neuroblastoma in Remission
- ClinicalTrials.gov ID
- NCT02395666
- Acronym / sponsor ID
- NMTRC003B
- Conditions
- Neuroblastoma
- Keywords
- Neuroblastoma in remission, Relapsed Neuroblastoma, Refractory Neuroblastoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 140 participants (actual)
- Lead sponsor
- Giselle ShollerUniversity, hospital or other
- Collaborators
- Beat NB Cancer Foundation, Because of Ezra, K C Pharmaceuticals Inc.
- Study start
- 5 Mar 2015 (actual)
- Primary completion
- 27 Mar 2018 (actual)
- Study completion
- 24 Aug 2023 (actual)
- First posted
- 23 Mar 2015 (estimated)
- Results
- Posted 3 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to evaluate a new investigational drug to prevent reoccurrence of neuroblastoma that is in remission. This study drug is called DFMO. The objectives of this study will be to monitor for safety and look at efficacy of DFMO.
The safety of the proposed dosing regimen in this trial will be tested by an on-going risk/benefit assessment during the study. A patient benefiting from treatment, not progressing on therapy, and in the absence of any safety issues associated with DFMO may continue on treatment up to 27 cycles with the expectation that there will be an overall clinical benefit.
The procedures involved in this study include Medical history, Physical exam, Vital signs (blood pressure, pulse, temperature), Blood tests, Urine tests, MRI or CT scan of the tumor(s), meta-iodobenzylguanidine (MIBG) scans, and Bone marrow aspirations. All of these tests and procedures are considered standard of care for this population. Drug administration is also part of this protocol, including an investigational new drug called DFMO.
The proposed dosing regimen is an oral dose of DFMO tablets two times a day for each day while on study. There will be 27 cycles. Each cycle will be 28 days in length.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DFMO twice daily | Experimental | Drug: DFMOSubjects will receive twenty-seven (27) cycles of oral DFMO at a dose of 500 to 1000 mg/m2 BID on each day of a 28 day cycle. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (12 listed)
- Age: 0-21 years at the time of diagnosis.
- Diagnosis: histologic verification at either the time of original diagnosis or a previous relapse of high risk neuroblastoma.
- Disease Status: Neuroblastoma that is in remission
- First dose of study medication must be greater than 30 days from completion of cytotoxic and antibody therapy and less than 120 days from previous therapy
- A negative serum or urine pregnancy test is required for female subjects of child bearing potential (onset of menses or ≥13 years of age).
Key exclusion criteria (6 listed)
- Lansky score < 60%
- Body Surface Area (BSA) (m2) of <0.25
- Investigational Drugs: Subjects who are currently receiving another investigational drug are excluded from participation.
- Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are not eligible. Subjects must have fully recovered from the effects of prior chemotherapy (hematological and bone marrow suppression effects).
- Infection: Subjects who have an uncontrolled infection are not eligible until the infection is judged to be well controlled in the opinion of the investigator.
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: eflornithine HCl, DifluoromethylornithineSubjects will receive twenty-seven (27) cycles of oral DFMO at a dose of 500 to 1000 mg/m2 BID on each day of a 28 day cycle. | Drug | DFMO twice daily |
Primary outcome
Number of Participants With Event Free Survival (EFS) During Study.
Time frame: 2 Years
To evaluate the preventative activity of DFMO as a single agent in patients that are in remission based on: Event free survival (EFS)
6 secondary outcomes
Percentage of Participants With Overall Survival (OS)
Time frame: 2 Years
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Time frame: 2 years
Test the Association of Survival With ODC1 Genotype
Time frame: 2 years
Peak Plasma Concentration (Cmax)
Time frame: Samples drawn at 5 timepoints: (0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose) on two different days
Area Under the Plasma Concentration Versus Time Curve (AUC)
Time frame: 0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose on two different days
Time to Reach Peak Plasma Concentration (Tmax)
Time frame: 0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose on two different days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38917371Duke ES, Bradford D, Sinha AK, Mishra-Kalyani PS, Lerro CC, Rivera D, Wearne E, Miller CP, Leighton J, Sabit H, Zhao H, Lane A, Scepura B, Pazdur R, Singh H, Kluetz PG, Donoghue M, Drezner N. US Food and Drug Administration Approval Summary: Eflornithine for High-Risk Neuroblastoma After Prior Multiagent, Multimodality Therapy. J Clin Oncol. 2024 Sep 1;42(25):3047-3057. doi: 10.1200/JCO.24.00546. Epub 2024 Jun 25.
- Derived from this study: PubMed 37883734Oesterheld J, Ferguson W, Kraveka JM, Bergendahl G, Clinch T, Lorenzi E, Berry D, Wada RK, Isakoff MS, Eslin DE, Brown VI, Roberts W, Zage P, Harrod VL, Mitchell DS, Hanson D, Saulnier Sholler GL. Eflornithine as Postimmunotherapy Maintenance in High-Risk Neuroblastoma: Externally Controlled, Propensity Score-Matched Survival Outcome Comparisons. J Clin Oncol. 2024 Jan 1;42(1):90-102. doi: 10.1200/JCO.22.02875. Epub 2023 Oct 26.
- Derived from this study: PubMed 34522028Urban-Wojciuk Z, Graham A, Barker K, Kwok C, Sbirkov Y, Howell L, Campbell J, Woster PM, Poon E, Petrie K, Chesler L. The biguanide polyamine analog verlindamycin promotes differentiation in neuroblastoma via induction of antizyme. Cancer Gene Ther. 2022 Jul;29(7):940-950. doi: 10.1038/s41417-021-00386-6. Epub 2021 Sep 14.
- Derived from this study: PubMed 32506485Batth IS, Dao L, Satelli A, Mitra A, Yi S, Noh H, Li H, Brownlee Z, Zhou S, Bond J, Wang J, Gill J, Sholler GS, Li S. Cell surface vimentin-positive circulating tumor cell-based relapse prediction in a long-term longitudinal study of postremission neuroblastoma patients. Int J Cancer. 2020 Dec 15;147(12):3550-3559. doi: 10.1002/ijc.33140. Epub 2020 Jun 23.
- Derived from this study: PubMed 32391579Lewis EC, Kraveka JM, Ferguson W, Eslin D, Brown VI, Bergendahl G, Roberts W, Wada RK, Oesterheld J, Mitchell D, Foley J, Zage P, Rawwas J, Rich M, Lorenzi E, Broglio K, Berry D, Saulnier Sholler GL. A subset analysis of a phase II trial evaluating the use of DFMO as maintenance therapy for high-risk neuroblastoma. Int J Cancer. 2020 Dec 1;147(11):3152-3159. doi: 10.1002/ijc.33044. Epub 2020 May 24.
- Beat Childhood Cancer Consortium websiteLink provided by the sponsor.
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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.
Giselle Saulnier-Sholler, MD study chair
Beat Childhood Cancer
22 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing DFMO in people with Neuroblastoma, run by Giselle Sholler at 22 sites in United States.
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 12 inclusion and 6 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 6 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Event Free Survival (EFS) During Study. (time frame: 2 Years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02395666, which also lists 5 linked publications.
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 6 Aug 2024.