NCT02395666 · CITED IN SOURCE DOCUMENTS

Preventative Trial of Difluoromethylornithine (DFMO) in High Risk Patients With Neuroblastoma That is in Remission

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE2
Status at capture: COMPLETED
Registry last update: 2024-08-06

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number of Participants With Event Free Survival (EFS) During Study.

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outcome · POSTED

Percentage of Participants With Overall Survival (OS)

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outcome · POSTED

Number of Participants With Adverse Events as a Measure of Safety and Tolerability

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outcome · POSTED

Test the Association of Survival With ODC1 Genotype

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outcome · POSTED

Peak Plasma Concentration (Cmax)

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outcome · POSTED

Area Under the Plasma Concentration Versus Time Curve (AUC)

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outcome · POSTED

Time to Reach Peak Plasma Concentration (Tmax)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * 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. * 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 Exclusion Criteria: * 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.
healthy Volunteers: false
maximum Age: 21 Years
sex: ALL
std Ages: CHILD
ADULT

Treatment arms and interventions

arm Groups

description
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.
intervention Names
Drug: DFMO
label
DFMO twice daily
type
EXPERIMENTAL

interventions

arm Group Labels
DFMO twice daily
description
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.
name
DFMO
other Names
eflornithine HCl
Difluoromethylornithine
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

PREVENTION

Enrollment

count: 140
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
To evaluate the preventative activity of DFMO as a single agent in patients that are in remission based on: Event free survival (EFS)
measure
Number of Participants With Event Free Survival (EFS) During Study.
time Frame
2 Years

secondary Outcomes

description
To evaluate the preventative activity of DFMO as a single agent in patients with neuroblastoma who are in remission based on: Overall Survival (OS)
measure
Percentage of Participants With Overall Survival (OS)
time Frame
2 Years
description
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.
measure
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
time Frame
2 years
description
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
measure
Test the Association of Survival With ODC1 Genotype
time Frame
2 years
description
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.
measure
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
description
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
measure
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
description
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
measure
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

Full study description

brief 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. 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.

Source references

references

citation
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.
pmid
38917371
type
DERIVED
citation
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pmid
37883734
type
DERIVED
citation
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pmid
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type
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citation
Batth 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.
pmid
32506485
type
DERIVED
citation
Lewis 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.
pmid
32391579
type
DERIVED