- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04696029
DFMO as Maintenance Therapy for Molecular High/Very High Risk and Relapsed Medulloblastoma
Phase II Trial of Eflornithine/DFMO as Maintenance Therapy for Molecular High Risk/Very High Risk and Relapsed/Refractory Medulloblastoma
Study Overview
Detailed Description
In this study subjects will receive 730 Days of oral difluoromethylornithine (DFMO) at a dose of 2500 mg/m2 BID on each day of study.
Subjects will be evaluated in 3 Cohorts:
Cohort 1: Molecular High Risk Medulloblastoma Cohort 2: Molecular Very High Risk Medulloblastoma Cohort 3: Relapsed/Refractory Medulloblastoma
A total of 118 subjects across all cohorts will be enrolled to ensure that there will be 107 evaluable subjects (32-39 per cohort)
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Genevieve Bergendahl, MSN
- Phone Number: 7175310003
- Email: gbergendahl@pennstatehealth.psu.edu
Study Locations
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Arkansas
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Little Rock, Arkansas, United States, 72202
- Recruiting
- Arkansas Children's Hospital
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Principal Investigator:
- Kevin Bielamowicz, MD
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Contact:
- Susan Hall
- Phone Number: 501-364-2760
- Email: HallSF@archildrens.org
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California
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Oakland, California, United States, 94609
- Recruiting
- UCSF Benioff Children's Hospital Oakland-
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Contact:
- Group Contact
- Email: PedOncRschOAK@ucsf.edu
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Principal Investigator:
- Jennifer Michlitsch, MD
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San Diego, California, United States, 92123
- Recruiting
- Rady Children's Hospital
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Principal Investigator:
- William Roberts, MD
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Contact:
- Franchesca Ramirez
- Phone Number: 858-966-8155
- Email: framirez@rchsd.org
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Connecticut
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Hartford, Connecticut, United States, 06106
- Not yet recruiting
- Connecticut Children's Hospital
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Principal Investigator:
- Michael Isakoff, MD
-
Contact:
- Nicole McCracken
- Phone Number: 860-545-9337
- Email: NMccracken@connecticutchildrens.org
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Florida
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Orlando, Florida, United States, 32806
- Recruiting
- Arnold Palmer Hospital for Children
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Principal Investigator:
- Amy Smith, MD
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Contact:
- Michelle Pellet
- Phone Number: 321-841-8588
- Email: Michelle.Pellett@orlandohealth.com
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Tampa, Florida, United States, 33607
- Recruiting
- St. Joseph's Children's Hospital
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Principal Investigator:
- Don Eslin, MD
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Contact:
- Jennifer Manns
- Email: Jennifer.Manns@baycare.org
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Kentucky
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Lexington, Kentucky, United States, 40502
- Recruiting
- Kentucky Children's Hospital
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Contact:
- Brittany Fuller
- Email: blfull2@email.uky.edu
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Principal Investigator:
- Tom Badgett, MD
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Louisville, Kentucky, United States, 40202
- Recruiting
- University of Louisville/Norton's Children's
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Contact:
- Michael A Huang, MD
- Phone Number: 502.852.8450
- Email: michael.huang@louisville.edu
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Principal Investigator:
- Huang A Michael, MD
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Contact:
- Jennifer Miller
- Email: Jennifer.Miller4@nortonhealthcare.org
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Missouri
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Kansas City, Missouri, United States, 64108
- Recruiting
- Children's Mercy Hospitals and Clinics
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Contact:
- Nicole Harvey
- Phone Number: 816-302-6893
- Email: ndharvey@cmh.edu
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Principal Investigator:
- Kevin Ginn, MD
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Saint Louis, Missouri, United States, 63104
- Not yet recruiting
- Cardinal Glennon Children's Medical Center
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Principal Investigator:
- William Ferguson, MD
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Contact:
- Gina Martin, RN
- Phone Number: 314-268-4000
- Email: gina.martin@health.slu.edu
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New Jersey
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Hackensack, New Jersey, United States, 07601
- Recruiting
- Hackensack University Medical Center
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Contact:
- Sherri Mayans
- Email: sherri.mayans@hmhn.org
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Principal Investigator:
- Derek Hanson, MD
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North Carolina
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Charlotte, North Carolina, United States, 28204
- Recruiting
- Levine Children's Hospital
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Principal Investigator:
- Thomas Russell, MD
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Contact:
- Jontyce Green
- Phone Number: 980-442-2356
- Email: jontyce.green@atriumhealth.org
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Pennsylvania
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Hershey, Pennsylvania, United States, 17033
- Recruiting
- Penn State Milton S. Hershey Medical Center and Children's Hospital
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Contact:
- Suzanne Treadway
- Email: streadway@hmc.psu.edu
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Principal Investigator:
- Valerie Brown, MD
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South Carolina
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Charleston, South Carolina, United States, 29425
- Recruiting
- Medical University of South Carolina
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Principal Investigator:
- Jaqueline Kraveka, MD
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Contact:
- Shanta Salzar, MD
- Phone Number: 843-792-2957
- Email: salzers@musc.edu
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Texas
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Austin, Texas, United States, 78723
- Recruiting
- Dell Children's Blood and Cancer Center
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Principal Investigator:
- Virginia Harrod, MD
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Contact:
- Rhea Robinson, RN
- Phone Number: 512-628-1902
- Email: TXAUS-DL-SFCHemonc.research@ascension.org
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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
- Bone Marrow aspiration/biopsy only if previously positive
- This disease assessment is required for eligibility and preferably should be done within 2 weeks prior to first dose of study drug, but must be done within a maximum of 4 weeks before first dose of study drug.
Disease Status: Subjects must have no evidence of disease, or stable* residual nonbulky** disease.
*Stable residual disease defined as non-progression over 2 separate imaging studies at least 6 weeks apart
**Non-bulky disease defined as maximal cross-sectional area < 3cm^2 at enrollment. Patients with leptomeningeal disease are allowed to participate on study.
Timing from prior therapy:
Enrollment (first dose of DFMO) no later than 60 days after last dose of conventional chemotherapy. Patients who have undergone high dose chemotherapy (HDCT) with autologous stem cell transplantation (SCT) are eligible if more than 45 days have elapsed since date of last SCT.
- Patients must have a Lansky or Karnofsky Performance Scale score of ≥ 50% (see Appendix II) and patients must have a life expectancy of ≥ 2 months.
- All clinical and laboratory studies for organ functions to determine eligibility must be performed within 7 days prior to first dose of study drug unless otherwise indicated below.
Patients must have adequate organ functions at the time of registration:
- Hematological: Hematological recovery as defined by ANC ≥750/μL, platelets ≥30 (non-transfused x 7 days)
- Liver: Adequate liver function as defined by AST and ALT <10x upper limit of normal
- Renal: Adequate renal function defined as (perform one of the following): Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m2 or a serum creatinine based on age/gender
- Females of childbearing potential must have a negative pregnancy test. Patients of childbearing potential must agree to use an effective birth control method. Female patients who are lactating must agree to stop breast-feeding.
- Written informed consent in accordance with institutional and FDA guidelines must be obtained from all subjects (or patients' legal representative).
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Difluoromethylornithine (DFMO)
study subjects will receive 730 Days of oral difluoromethylornithine (DFMO) at a dose of 2500 mg/m2 BID on each day of study.
|
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).
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of participants with event free survival (EFS) during study
Time Frame: 2 years plus 5 years follow up
|
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.
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2 years plus 5 years follow up
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Length of time that participants experience Overall Survival (OS)
Time Frame: 7 years
|
o To evaluate the efficacy of difluoromethylornithine (DFMO) as a single agent in patients with molecular high risk and very high risk medulloblastoma, and relapsed/refractory medulloblastoma based upon overall survival
|
7 years
|
Determine the Overall Response Rate (ORR) of Participants using Modified RANO Criteria
Time Frame: 2 years
|
To evaluate the efficacy of difluoromethylornithine (DFMO) as a single agent in patients with molecular high risk and very high risk medulloblastoma, and relapsed/refractory medulloblastoma based upon Response Rate for patients with non-bulky residual disease present.
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2 years
|
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time Frame: 2 years plus 30 days
|
To develop a complete safety and tolerability profile of difluoromethylornithine (DFMO) in pediatric and young adult subjects with medulloblastoma.
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2 years plus 30 days
|
Determine amount of DFMO in the CSF at 3 hours post dose
Time Frame: 2 years
|
o To measure CSF penetration after DFMO administration in pediatric subjects with medulloblastoma
|
2 years
|
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Michael A Huang, MD, Beat Childhood Cancer at Atrium Health
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Glandular and Epithelial
- Glioma
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroectodermal Tumors, Primitive
- Medulloblastoma
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antineoplastic Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Trypanocidal Agents
- Ornithine Decarboxylase Inhibitors
- Eflornithine
Other Study ID Numbers
- BCC016
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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