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

Neuroblastoma Clinical Trial

Official title:

A Phase II Preventative Trial of DFMO (Eflornithine HCl) as a Single Agent in Patients With High Risk Neuroblastoma in Remission

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02395666
• Other study ID #: NMTRC003B
• Status: Completed
• Phase: Phase 2
• Start date: March 5, 2015
• Est. completion date: August 24, 2023

Study information

• Verified date: April 2024
• Source: Milton S. Hershey Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Other known NCT identifiers

• NCT01586260

Recruitment information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: August 24, 2023
• Est. primary completion date: March 27, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Years

Eligibility

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.

Related Conditions & MeSH terms

• Neuroblastoma

Intervention

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.

Locations

Country	Name	City	State
United States	Dell Children's Blood and Cancer Center	Austin	Texas
United States	Tufts Medical Center	Boston	Massachusetts
United States	The Children's Hospital at Montefiore	Bronx	New York
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Levine Children's Hospital	Charlotte	North Carolina
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Children's Medical Center	Dallas	Texas
United States	Helen DeVos Children's Hospital	Grand Rapids	Michigan
United States	Connecticut Children's Hospital	Hartford	Connecticut
United States	Penn State Milton S. Hershey Medical Center and Children's Hospital	Hershey	Pennsylvania
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Texas Children's Cancer and Hematology Centers	Houston	Texas
United States	Children's Mercy Hospitals and Clinics	Kansas City	Missouri
United States	Arkansas Children's Hospital	Little Rock	Arkansas
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	Arnold Palmer Hospital for Children	Orlando	Florida
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Cardinal Glennon Children's Medical Center	Saint Louis	Missouri
United States	All Children's Hospital Johns Hopkins Medicine	Saint Petersburg	Florida
United States	Primary Children's Hospital	Salt Lake City	Utah
United States	Rady Children's Hospital	San Diego	California

Sponsors (4)

Lead Sponsor	Collaborator
Giselle Sholler	Beat NB Cancer Foundation, Because of Ezra, K C Pharmaceuticals Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Event Free Survival (EFS) During Study.	To evaluate the preventative activity of DFMO as a single agent in patients that are in remission based on: Event free survival (EFS)	2 Years
Secondary	Percentage of Participants With Overall Survival (OS)	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 Years
Secondary	Number of Participants With Adverse Events as a Measure of Safety and Tolerability	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.	2 years
Secondary	Test the Association of Survival With ODC1 Genotype	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	2 years
Secondary	Peak Plasma Concentration (Cmax)	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.	Samples drawn at 5 timepoints: (0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose) on two different days
Secondary	Area Under the Plasma Concentration Versus Time Curve (AUC)	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	0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose on two different days
Secondary	Time to Reach Peak Plasma Concentration (Tmax)	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	0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose on two different days

External Links

•   Beat Childhood Cancer Consortium website