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

Phase 2

Completed

• Conditions: Neuroblastoma
• Interventions: Drug: DFMO

• Registration Number: NCT02395666
• Lead Sponsor: Giselle Sholler

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Related News

Study Timeline

• Study Start: 2015-03-05
• Study First Submitted: 2015-03-05
• Study First Submitted QC: 2015-03-20
• Study First Posted: 2015-03-23
• Primary Completion: 2018-03-27
• Results First Submitted: 2020-02-14
• Results First Submitted QC: 2020-04-01
• Results First Posted: 2020-04-03
• Study Completion: 2023-08-24
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-02
• Last Update Posted: 2024-08-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 140

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
DFMO twice daily	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.

Primary Outcome Measures

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

Name	Time	Method
Test the Association of Survival With ODC1 Genotype	2 years	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
Number of Participants With Adverse Events as a Measure of Safety and Tolerability	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.
Percentage of Participants With Overall Survival (OS)	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)
Area Under the Plasma Concentration Versus Time Curve (AUC)	0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose on two different days	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 to Reach Peak Plasma Concentration (Tmax)	0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose on two different days	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
Peak Plasma Concentration (Cmax)	Samples drawn at 5 timepoints: (0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose) on two different days	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.

Trial Locations

Locations (22)

Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States

Rady Children's Hospital; 🇺🇸 San Diego, California, United States

Children's Hospital and Clinics on Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

Monroe Carrell Jr. Children's Hospital at Vanderbilt; 🇺🇸 Nashville, Tennessee, United States

Dell Children's Blood and Cancer Center; 🇺🇸 Austin, Texas, United States

Helen DeVos Children's Hospital; 🇺🇸 Grand Rapids, Michigan, United States

All Children's Hospital Johns Hopkins Medicine; 🇺🇸 Saint Petersburg, Florida, United States

Cardinal Glennon Children's Medical Center; 🇺🇸 Saint Louis, Missouri, United States

Levine Children's Hospital; 🇺🇸 Charlotte, North Carolina, United States

Penn State Milton S. Hershey Medical Center and Children's Hospital; 🇺🇸 Hershey, Pennsylvania, United States

Children's Medical Center; 🇺🇸 Dallas, Texas, United States

Texas Children's Cancer and Hematology Centers; 🇺🇸 Houston, Texas, United States

Primary Children's Hospital; 🇺🇸 Salt Lake City, Utah, United States

Arnold Palmer Hospital for Children; 🇺🇸 Orlando, Florida, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

Children's Mercy Hospitals and Clinics; 🇺🇸 Kansas City, Missouri, United States

Arkansas Children's Hospital; 🇺🇸 Little Rock, Arkansas, United States

Nationwide Children's Hospital; 🇺🇸 Columbus, Ohio, United States

Phoenix Children's Hospital; 🇺🇸 Phoenix, Arizona, United States

Connecticut Children's Hospital; 🇺🇸 Hartford, Connecticut, United States

Kapiolani Medical Center for Women and Children; 🇺🇸 Honolulu, Hawaii, United States

The Children's Hospital at Montefiore; 🇺🇸 Bronx, New York, United States