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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2016 by Spectrum Health Hospitals
Sponsor:
Collaborators:
Beat NB Cancer Foundation
Because of Ezra
Information provided by (Responsible Party):
Giselle Sholler, Spectrum Health Hospitals
ClinicalTrials.gov Identifier:
NCT02395666
First received: March 5, 2015
Last updated: February 16, 2016
Last verified: February 2016
  Purpose

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 Intervention Phase
Neuroblastoma
Drug: DFMO
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Spectrum Health Hospitals:

Primary Outcome Measures:
  • Number of participants with event free survival (EFS) during study. [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
    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:
  • Length of time that participants experience Overall Survival (OS) [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
    To evaluate the preventative activity of DFMO as a single agent in patients with neuroblastoma who are in remission based on: Overall Survival (OS)

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

  • Number of participants with ODC single nucleotide polymorphisms. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Blood: microRNA analysis as predictor of DFMO effect, ornithine decarboxylase (ODC) single nucleotide polymorphism (SNP) analysis in DNA isolated from nucleated cells

  • Polyamine Levels in Urine and blood [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Urine: polyamine levels and blood inflammatory markers

  • Biomarker Analysis using antibody array analysis [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    explorative biomarker analysis

  • Circulating Tumor Cell Analysis [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    circulating tumor cell analysis

  • Immunophenotyping of bone marrow samples [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Immunophenotyping of bone marrow samples for evaluation of minimal residual disease present in bone marrow.

  • Peak Plasma Concentration (Cmax) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Pharmacokinetic assay

  • Area under the plasma concentration versus time curve (AUC) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Pharmacokinetic assay

  • Time to reach Peak Plasma Concentration (Tmax) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Pharmacokinetic assay


Estimated Enrollment: 160
Study Start Date: March 2015
Estimated Study Completion Date: March 2021
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02395666

Contacts
Contact: Genevieve Bergendahl, RN 616-267-0335 genevieve.bergendahl@helendevoschildrens.org
Contact: Alyssa VanderWerff (616) 267-0327 alyssa.vanderwerff@helendevoschildrens.org

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

Additional Information:
Responsible Party: Giselle Sholler, NMTRC Chair, Spectrum Health Hospitals
ClinicalTrials.gov Identifier: NCT02395666     History of Changes
Other Study ID Numbers: NMTRC003B 
Study First Received: March 5, 2015
Last Updated: February 16, 2016
Health Authority: United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on August 25, 2016