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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02395666
Recruitment Status : Active, not recruiting
First Posted : March 23, 2015
Last Update Posted : July 10, 2018
Beat NB Cancer Foundation
Because of Ezra
Information provided by (Responsible Party):
Giselle Sholler, Spectrum Health Hospitals

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.

Condition or disease Intervention/treatment Phase
Neuroblastoma Drug: DFMO Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 142 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Phase II Preventative Trial of DFMO (Eflornithine HCl) as a Single Agent in Patients With High Risk Neuroblastoma in Remission
Study Start Date : March 2015
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : March 2021

Arm Intervention/treatment
Experimental: DFMO twice daily
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.
Other Names:
  • eflornithine HCl
  • Difluoromethylornithine

Primary Outcome Measures :
  1. 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)

Secondary Outcome Measures :
  1. Length of time that participants experience Overall Survival (OS) [ Time Frame: 2 Years ]
    To evaluate the preventative activity of DFMO as a single agent in patients with neuroblastoma who are in remission based on: Overall Survival (OS)

  2. Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 2 years ]
    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.

  3. Number of participants with ODC single nucleotide polymorphisms. [ Time Frame: 2 years ]
    Blood: microRNA analysis as predictor of DFMO effect, ornithine decarboxylase (ODC) single nucleotide polymorphism (SNP) analysis in DNA isolated from nucleated cells

  4. Polyamine Levels in Urine and blood [ Time Frame: 2 years ]
    Urine: polyamine levels and blood inflammatory markers

  5. Biomarker Analysis using antibody array analysis [ Time Frame: 2 years ]
    explorative biomarker analysis

  6. Circulating Tumor Cell Analysis [ Time Frame: 2 years ]
    circulating tumor cell analysis

  7. Immunophenotyping of bone marrow samples [ Time Frame: 2 years ]
    Immunophenotyping of bone marrow samples for evaluation of minimal residual disease present in bone marrow.

  8. Peak Plasma Concentration (Cmax) [ Time Frame: 2 years ]
    Pharmacokinetic assay

  9. Area under the plasma concentration versus time curve (AUC) [ Time Frame: 2 years ]
    Pharmacokinetic assay

  10. Time to reach Peak Plasma Concentration (Tmax) [ Time Frame: 2 years ]
    Pharmacokinetic assay

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02395666

  Show 21 Study Locations
Sponsors and Collaborators
Giselle Sholler
Beat NB Cancer Foundation
Because of Ezra
Study Chair: Giselle Saulnier-Sholler, MD The Spectrum Health Group

Responsible Party: Giselle Sholler, NMTRC Chair, Spectrum Health Hospitals Identifier: NCT02395666     History of Changes
Other Study ID Numbers: NMTRC003B
First Posted: March 23, 2015    Key Record Dates
Last Update Posted: July 10, 2018
Last Verified: July 2018

Keywords provided by Giselle Sholler, Spectrum Health Hospitals:
Neuroblastoma in remission
Relapsed Neuroblastoma
Refractory Neuroblastoma

Additional relevant MeSH terms:
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Antineoplastic Agents
Trypanocidal Agents
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Ornithine Decarboxylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action