A Phase 2 interventional study of DFMO in Neuroblastoma, sponsored by Giselle Sholler. Completed at 22 sites in United States. Open to participants aged Up to 21 Years. Per ClinicalTrials.gov, last updated 2024-08-06.
Sponsored by Giselle Sholler · Phase 2, Interventional, and Prevention
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.
625 studies on the registry are indexed under Neuroblastoma; 122 are open to participants now.
This study's enrollment of 140 is above the median of 32 across 475 interventional studies indexed under Neuroblastoma.
Browse Neuroblastoma studies →Giselle Sholler is the lead sponsor of 22 studies on the registry; 6 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Organ Function Requirements: Subjects must have adequate liver function as defined by:
Exclusion Criteria:
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.
Drug: DFMO
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.
Also known as: eflornithine HCl, Difluoromethylornithine
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)
Time frame: 2 Years
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)
Time frame: 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.
Time frame: 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
Time frame: 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.
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)
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
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)
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
Time frame: 0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose on two different days
| Milestone | Stratum 1 | Stratum 2 |
|---|---|---|
| Started | 101 | 39 |
| Completed | 95 | 38 |
| Not completed | 6 | 1 |
| Withdrew: Physician decision | 3 | 0 |
| Withdrew: Lost to follow-up | 1 | 0 |
| Withdrew: Withdrawal by subject | 2 | 1 |
To evaluate the preventative activity of DFMO as a single agent in patients that are in remission based on: Event free survival (EFS)
| percentage of subjects without an event | Stratum 1 | Stratum 2 |
|---|---|---|
| Number of Participants With Event Free Survival (EFS) During Study. | 84 (80 to 88) | 51 (43 to 59) |
To evaluate the preventative activity of DFMO as a single agent in patients with neuroblastoma who are in remission based on: Overall Survival (OS)
| percentage of subjects without an event | Stratum 1 | Stratum 2 |
|---|---|---|
| Percentage of Participants With Overall Survival (OS) | 97 (95 to 99) | 84 (78 to 90) |
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.
| Participants | DFMO Twice Daily |
|---|---|
| Number of Participants With Adverse Events as a Measure of Safety and Tolerability | 57 |
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
| p-value | GG, GT, TT | GG or GT, TT | GG, GT or TT |
|---|---|---|---|
| Test the Association of Survival With ODC1 Genotype | 0.96 | 0.58 | 0.67 |
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.
| ng/mL | Study Subjects Consented to PK Collection |
|---|---|
| Peak Plasma Concentration (Cmax) | 11958 (5123 to 18793) |
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
| hr*ng/mL | Study Subjects Consented to PK Collection |
|---|---|
| Area Under the Plasma Concentration Versus Time Curve (AUC) | 47024 (23868 to 70180) |
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
| hours | Study Subjects Consented to PK Collection |
|---|---|
| Time to Reach Peak Plasma Concentration (Tmax) | 3.3 (1.9 to 4.7) |
Collected over Through study completion plus 30 days, an average of 2 years.. Non-serious events are listed at a 4% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| All Study Subjects | 0/140 (0%) | 23/140 (16.4%) | 41/140 (29.3%) |
| Event | All Study Subjects |
|---|---|
| InfectionInfections and infestations | 8/140 |
| VomitingGastrointestinal disorders | 3/140 |
| DiarrheaGastrointestinal disorders | 3/140 |
| PainGeneral disorders | 1/140 |
| FeverGeneral disorders | 1/140 |
| HyponatremiaInvestigations | 1/140 |
| Benign vascular lesionVascular disorders | 1/140 |
| Swelling of EyeEye disorders | 1/140 |
| HypoglycemiaMetabolism and nutrition disorders | 1/140 |
| UrticariaSkin and subcutaneous tissue disorders | 1/140 |
| Event | All Study Subjects |
|---|---|
| ALT elevationHepatobiliary disorders | 14/140 |
| Neutrophil count decreaseBlood and lymphatic system disorders | 11/140 |
| AST elevationHepatobiliary disorders | 10/140 |
| DiarrheaGastrointestinal disorders | 9/140 |
| Hearing LossEar and labyrinth disorders | 9/140 |
| AnemiaBlood and lymphatic system disorders | 6/140 |
| Otitis MediaInfections and infestations | 6/140 |
| Age, Continuous(years) | Stratum 1 | Stratum 2 | Total |
|---|---|---|---|
| Mean | 4.4 (1 to 17) | 6.8 (1 to 14) | 5.1 (1 to 17) |
| Sex: Female, Male(Participants) | Stratum 1 | Stratum 2 | Total |
|---|---|---|---|
| Female | 44 | 11 | 55 |
| Male | 57 | 28 | 85 |
| Race (NIH/OMB)(Participants) | Stratum 1 | Stratum 2 | Total |
|---|---|---|---|
| American Indian or Alaska Native | 2 | 1 | 3 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 7 | 3 | 10 |
| White | 82 | 32 | 114 |
| More than one race | 3 | 0 | 3 |
| Unknown or Not Reported | 7 | 3 | 10 |
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Giselle Sholler