DFMO as Maintenance Therapy for Molecular High/Very High Risk and Relapsed Medulloblastoma

NCT04696029 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: BCC016
• Study Type: interventional
• Target: 118
• Locations: 2 countries
• Sites: 24

Brief Summary

Difluoromethylornithine (DFMO) will be used in an open label, multicenter, study as Maintenance Therapy for Molecular High Risk/Very High Risk and Relapsed/Refractory Medulloblastoma.

Conditions

Medulloblastoma

Outcome Measures

Primary Outcomes (1)

• Number of participants with event free survival (EFS) during study

  o To evaluate the efficacy of difluoromethylornithine (DFMO) as a single agent in preventing relapse in patients with molecular high risk and very high risk medulloblastoma, and relapsed/refractory medulloblastoma based upon the 2-year progression-free survival rate (PFS) compared to relevant historical controls.

  2 years plus 5 years follow up

Secondary Outcomes (4)

• Length of time that participants experience Overall Survival (OS)

  7 years

• Determine the Overall Response Rate (ORR) of Participants using Modified RANO Criteria

  2 years

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

  2 years plus 30 days

• Determine amount of DFMO in the CSF at 3 hours post dose

  2 years

Study Arms (1)

Difluoromethylornithine (DFMO)

EXPERIMENTAL

study subjects will receive 730 Days of oral difluoromethylornithine (DFMO) at a dose of 2500 mg/m2 BID on each day of study.

Drug: Difluoromethylornithine

Interventions

Difluoromethylornithine DRUG

DFMO (difluoromethylornithine is an inhibitor of ornithine decarboxylase (ODC) designated chemically as 2-(difluoromethyl)-DL-ornithine monohydrochloride monohydrate. The dosage form to be used in this study is provided as a convex tablet containing 192 mg eflornithine (equivalent to 250 mg of eflornithine HCl, monohydrate). The tablets are packaged and sealed in opaque white HDPE bottles, and each bottle contains 100 tablets. The DMFO tablets are supplied by USWorldMeds (USWM). The tablets are to be stored at room temperature (20-250C).

Also known as: Eflornithine, DFMO

Difluoromethylornithine (DFMO)

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 of age at diagnosis
• Pathology All patients must either have a pathologically confirmed diagnosis of medulloblastoma with molecular grouping identified by either Nanostring or methylation profiling.
• Cohort 1- Molecular High Risk:
• Metastatic non-MYC amplified Group 3
• Metastatic Group 4
• Metastatic non-WNT/non-SHH (Must be non-MYC amplified)
• Cohort 2- Molecular Very High Risk
• Metastatic OR MYCN amplified OR TP53 mutant non-infant (\>3 yrs) SHH
• MYC amplified Group 3
• Non-WNT, non-SHH infant (\< 3 yrs)
• Cohort 3: Relapsed/Refractory Medulloblastoma
• Pre-enrollment tumor survey:
• Prior to enrollment on this study, a determination of mandatory disease staging must be performed:
• Tumor imaging studies including: Brain and spine MRI
• Lumbar Puncture only if previously positive

You may not qualify if:

• BSA of \<0.25 m2
• Metastatic disease outside of CNS
• Relapsed/refractory patients who are radiation-naïve and age 5 years or older at time of enrollment
• 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 hematological and bone marrow suppression effects of prior chemotherapy.
• 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

Study Sites (24)

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

RECRUITING

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

RECRUITING

Rady Children's Hospital

San Diego, California, 92123, United States

RECRUITING

Stanford University

Stanford, California, 94305, United States

RECRUITING

Connecticut Children's Hospital

Hartford, Connecticut, 06106, United States

RECRUITING

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

RECRUITING

Arnold Palmer Hospital for Children

Orlando, Florida, 32806, United States

RECRUITING

All Children's Hospital Johns Hopkins Medicine

St. Petersburg, Florida, 33701, United States

RECRUITING

St. Joseph's Children's Hospital

Tampa, Florida, 33607, United States

RECRUITING

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, 96813, United States

RECRUITING

Advocate Aurora Research Institute

Chicago, Illinois, 60453, United States

RECRUITING

Kentucky Children's Hospital

Lexington, Kentucky, 40502, United States

RECRUITING

Norton Children's Research Institute/Affiliated with University of Louisville School of Medicine

Louisville, Kentucky, 40202, United States

RECRUITING

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, 64108, United States

RECRUITING

Cardinal Glennon Children's Medical Center

St Louis, Missouri, 63104, United States

RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

RECRUITING

Levine Children's Hospital

Charlotte, North Carolina, 28204, United States

RECRUITING

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Randall Children's Hospital

Portland, Oregon, 97227, United States

RECRUITING

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

Hershey, Pennsylvania, 17033, United States

RECRUITING

Hasbro Children's Hospital

Providence, Rhode Island, 02903, United States

RECRUITING

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

Dell Children's Blood and Cancer Center

Austin, Texas, 78723, United States

RECRUITING

CHUQ

Québec, Quebec, QC G1V 4W6, Canada

RECRUITING

Related Links

• Beat Childhood Cancer Consortium website

MeSH Terms

Conditions

Medulloblastoma

Interventions

Eflornithine

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors, Primitive; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

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

Study Officials

• Michael A Huang, MD

  Beat Childhood Cancer

  STUDY CHAIR

Central Study Contacts

BCC Enroll

CONTACT

7175310003; BCCEnroll@pennstatehealth.psu.edu

Study Design

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

Study Record Dates

• First Submitted: January 4, 2021
• First Posted: January 6, 2021
• Study Start: March 29, 2021
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2029
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (23)