Preventative Trial of DFMO in Patients With High Risk Neuroblastoma in Remission

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Cancer Prevention Pharmaceuticals, Inc.
University of Arizona
University of Hawaii
University of Vermont
Beat NB Cancer Foundation
Information provided by (Responsible Party):
Giselle Sholler, Spectrum Health Hospitals
ClinicalTrials.gov Identifier:
NCT01586260
First received: April 24, 2012
Last updated: April 1, 2015
Last verified: April 2015
  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), 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 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:
  • 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 ] [ Designated as safety issue: No ]
    3.1.1 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:
  • 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 ] [ 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.

  • Biology studies [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Biological Correlates to minimally include: 1) Urine: polyamine levels and blood inflammatory markers, 2) Blood: microRNA analysis as predictor of DFMO effect, ODC SNP analysis in DNA isolated from nucleated cells, explorative biomarker analysis 3) Bone Marrow: flow cytometry of minimal residual disease of tumor; explorative biomarker analysis


Estimated Enrollment: 160
Study Start Date: June 2012
Estimated Study Completion Date: June 2020
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
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
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
  • Greater than 30 days from completion of cytotoxic and biologic therapy and less than 120 days from previous therapy.
  • A negative 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), levonorgestrol implants (Norplant), or medroxyprogesterone acetate injections (Depo-provera shots). If one of these cannot be used, contraceptive foam with a condom is recommended.
  • ANC > 500/μl and platelet count >50,000/μl
  • Organ Function Requirements: Subjects must have adequate liver function as defined by:

    • AST and 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%
  • 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: NCT01586260

Locations
United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States, 85016
United States, California
Rady Children's Hospital
San Diego, California, United States, 92123
United States, Connecticut
Connecticut Children's Hospital
Hartford, Connecticut, United States, 06106
United States, Florida
Arnold Palmer Hospital for Children- MD Anderson
Orlando, Florida, United States, 32806
United States, Hawaii
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, United States, 96813
United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States, 02111
United States, Michigan
Helen DeVos Children's Hospital
Grand Rapids, Michigan, United States, 49503
United States, Minnesota
Children's Hospital and Clinics on Minnesota
Minneapolis, Minnesota, United States, 55404
United States, Missouri
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, United States, 64108
Cardinal Glennon Children's Medical Center
St. Louis, Missouri, United States, 63104
United States, North Carolina
Levine Children's Hospital
Charlotte, North Carolina, United States, 28204
United States, Pennsylvania
Penn State Milton S. Hershey Medical Center and Children's Hospital
Hershey, Pennsylvania, United States, 17033
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Texas
Dell Children's Blood and Cancer Center
Austin, Texas, United States, 78723
Children's Medical Center
Dallas, Texas, United States, 75235
Texas Children's Cancer and Hematology Centers
Houston, Texas, United States, 77030
United States, Utah
Primary Children's Hospital
Salt Lake City, Utah, United States, 84113
Sponsors and Collaborators
Giselle Sholler
Cancer Prevention Pharmaceuticals, Inc.
University of Arizona
University of Hawaii
University of Vermont
Beat NB Cancer Foundation
Investigators
Study Chair: Giselle Sholler, MD The Spectrum Health Group
  More Information

Additional Information:
No publications provided

Responsible Party: Giselle Sholler, Study Chair, Spectrum Health Hospitals
ClinicalTrials.gov Identifier: NCT01586260     History of Changes
Other Study ID Numbers: NMTRC 003
Study First Received: April 24, 2012
Last Updated: April 1, 2015
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
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral
Eflornithine
Anti-Infective Agents
Antineoplastic Agents
Antiparasitic Agents
Antiprotozoal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Trypanocidal Agents

ClinicalTrials.gov processed this record on July 30, 2015