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

NCT02395666 | Completed Phase 2 Results DMC

• 1 other identifier: NMTRC003B
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 22

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.

Conditions

Neuroblastoma

Keywords

Neuroblastoma in remission; Relapsed Neuroblastoma; Refractory Neuroblastoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Percentage of Participants With Overall Survival (OS)

  2 Years

• Number of Participants With Adverse Events as a Measure of Safety and Tolerability

  2 years

• Test the Association of Survival With ODC1 Genotype

  2 years

• 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

• 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

Study Arms (1)

DFMO twice daily

EXPERIMENTAL

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

Interventions

DFMO DRUG

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.

Also known as: eflornithine HCl, Difluoromethylornithine

DFMO twice daily

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Giselle Sholler: lead
• Beat NB Cancer Foundation: collaborator
• Because of Ezra: collaborator
• K C Pharmaceuticals Inc.: collaborator

Study Sites (22)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Rady Children's Hospital

San Diego, California, 92123, United States

Location

Connecticut Children's Hospital

Hartford, Connecticut, 06106, United States

Location

Arnold Palmer Hospital for Children

Orlando, Florida, 32806, United States

Location

All Children's Hospital Johns Hopkins Medicine

St. Petersburg, Florida, 33701, United States

Location

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, 96813, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Helen DeVos Children's Hospital

Grand Rapids, Michigan, 49503, United States

Location

Children's Hospital and Clinics on Minnesota

Minneapolis, Minnesota, 55404, United States

Location

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, 64108, United States

Location

Cardinal Glennon Children's Medical Center

St Louis, Missouri, 63104, United States

Location

The Children's Hospital at Montefiore

The Bronx, New York, 10467, United States

Location

Levine Children's Hospital

Charlotte, North Carolina, 28204, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Penn State Milton S. Hershey Medical Center and Children's Hospital

Hershey, Pennsylvania, 17033, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Monroe Carrell Jr. Children's Hospital at Vanderbilt

Nashville, Tennessee, 37232, United States

Location

Dell Children's Blood and Cancer Center

Austin, Texas, 78723, United States

Location

Children's Medical Center

Dallas, Texas, 75235, United States

Location

Texas Children's Cancer and Hematology Centers

Houston, Texas, 77030, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

Related Publications (5)

• Duke ES, Bradford D, Sinha AK, Mishra-Kalyani PS, Lerro CC, Rivera D, Wearne E, Miller CP, Leighton J, Sabit H, Zhao H, Lane A, Scepura B, Pazdur R, Singh H, Kluetz PG, Donoghue M, Drezner N. US Food and Drug Administration Approval Summary: Eflornithine for High-Risk Neuroblastoma After Prior Multiagent, Multimodality Therapy. J Clin Oncol. 2024 Sep 1;42(25):3047-3057. doi: 10.1200/JCO.24.00546. Epub 2024 Jun 25.

  PMID: 38917371 DERIVED

• Oesterheld J, Ferguson W, Kraveka JM, Bergendahl G, Clinch T, Lorenzi E, Berry D, Wada RK, Isakoff MS, Eslin DE, Brown VI, Roberts W, Zage P, Harrod VL, Mitchell DS, Hanson D, Saulnier Sholler GL. Eflornithine as Postimmunotherapy Maintenance in High-Risk Neuroblastoma: Externally Controlled, Propensity Score-Matched Survival Outcome Comparisons. J Clin Oncol. 2024 Jan 1;42(1):90-102. doi: 10.1200/JCO.22.02875. Epub 2023 Oct 26.

  PMID: 37883734 DERIVED

• Urban-Wojciuk Z, Graham A, Barker K, Kwok C, Sbirkov Y, Howell L, Campbell J, Woster PM, Poon E, Petrie K, Chesler L. The biguanide polyamine analog verlindamycin promotes differentiation in neuroblastoma via induction of antizyme. Cancer Gene Ther. 2022 Jul;29(7):940-950. doi: 10.1038/s41417-021-00386-6. Epub 2021 Sep 14.

  PMID: 34522028 DERIVED

• Batth IS, Dao L, Satelli A, Mitra A, Yi S, Noh H, Li H, Brownlee Z, Zhou S, Bond J, Wang J, Gill J, Sholler GS, Li S. Cell surface vimentin-positive circulating tumor cell-based relapse prediction in a long-term longitudinal study of postremission neuroblastoma patients. Int J Cancer. 2020 Dec 15;147(12):3550-3559. doi: 10.1002/ijc.33140. Epub 2020 Jun 23.

  PMID: 32506485 DERIVED

• Lewis EC, Kraveka JM, Ferguson W, Eslin D, Brown VI, Bergendahl G, Roberts W, Wada RK, Oesterheld J, Mitchell D, Foley J, Zage P, Rawwas J, Rich M, Lorenzi E, Broglio K, Berry D, Saulnier Sholler GL. A subset analysis of a phase II trial evaluating the use of DFMO as maintenance therapy for high-risk neuroblastoma. Int J Cancer. 2020 Dec 1;147(11):3152-3159. doi: 10.1002/ijc.33044. Epub 2020 May 24.

  PMID: 32391579 DERIVED

Related Links

• Beat Childhood Cancer Consortium website

MeSH Terms

Conditions

Neuroblastoma

Interventions

Eflornithine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Ornithine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino

Results Point of Contact

• Title: Dr. Giselle Sholler
• Organization: Beat Childhood Cancer

Giselle.Saulniersholler@atriumhealth.org

704-381-9900

Study Officials

• Giselle Saulnier-Sholler, MD

  Beat Childhood Cancer

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Beat Childhood Cancer Chair

Study Record Dates

• First Submitted: March 5, 2015
• First Posted: March 23, 2015
• Study Start: March 5, 2015
• Primary Completion: March 27, 2018
• Study Completion: August 24, 2023
• Last Updated: August 6, 2024
• Results First Posted: April 3, 2020

Record last verified: 2024-08

Locations

US (22)