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

Sponsor
Wake Forest University Health Sciences (Other)
Overall Status
Recruiting
CT.gov ID
NCT04696029
Collaborator
(none)
118
Enrollment
13
Locations
1
Arm
95.1
Anticipated Duration (Months)
9.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Anticipated Enrollment :
118 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II Trial of Eflornithine/DFMO as Maintenance Therapy for Molecular High Risk/Very High Risk and Relapsed/Refractory Medulloblastoma
Actual Study Start Date :
Mar 29, 2021
Anticipated Primary Completion Date :
Mar 1, 2028
Anticipated Study Completion Date :
Mar 1, 2029

Arms and Interventions

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.

Drug: Difluoromethylornithine
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:
  • Eflornithine
  • DFMO

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of participants with event free survival (EFS) during study [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.

    Secondary Outcome Measures

    1. Length of time that participants experience Overall Survival (OS) [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

    2. Determine the Overall Response Rate (ORR) of Participants using Modified RANO Criteria [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.

    3. Number of Participants with Adverse Events as a Measure of Safety and Tolerability [2 years plus 30 days]

      To develop a complete safety and tolerability profile of difluoromethylornithine (DFMO) in pediatric and young adult subjects with medulloblastoma.

    4. Determine amount of DFMO in the CSF at 3 hours post dose [2 years]

      o To measure CSF penetration after DFMO administration in pediatric subjects with medulloblastoma

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A to 21 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Age: 0-21 years of age at diagnosis

    2. 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

    1. 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.

    1. 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.

    1. 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.

    1. 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.

    2. 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.

    3. 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

    1. 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.

    2. Written informed consent in accordance with institutional and FDA guidelines must be obtained from all subjects (or patients' legal representative).

    Exclusion Criteria:

    1. BSA of <0.25 m2

    2. Metastatic disease outside of CNS

    3. Relapsed/refractory patients who are radiation-naïve and age 5 years or older at time of enrollment

    4. Investigational Drugs: Subjects who are currently receiving another investigational drug are excluded from participation.

    5. 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.

    6. 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.

    7. 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Arkansas Children's Hospital Little Rock Arkansas United States 72202
    2 UCSF Benioff Children's Hospital Oakland- Oakland California United States 94609
    3 Connecticut Children's Hospital Hartford Connecticut United States 06106
    4 Arnold Palmer Hospital for Children Orlando Florida United States 32806
    5 St. Joseph's Children's Hospital Tampa Florida United States 33607
    6 Norton Children's Hospital/University of Louisville Louisville Kentucky United States 40202
    7 Children's Mercy Hospitals and Clinics Kansas City Missouri United States 64108
    8 Cardinal Glennon Children's Medical Center Saint Louis Missouri United States 63104
    9 Hackensack University Medical Center Hackensack New Jersey United States 07601
    10 Levine Children's Hospital Charlotte North Carolina United States 28204
    11 Penn State Milton S. Hershey Medical Center and Children's Hospital Hershey Pennsylvania United States 17033
    12 Medical University of South Carolina Charleston South Carolina United States 29425
    13 Dell Children's Blood and Cancer Center Austin Texas United States 78723

    Sponsors and Collaborators

    • Wake Forest University Health Sciences

    Investigators

    • Study Chair: Michael A Huang, MD, Beat Childhood Cancer at Atrium Health

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Wake Forest University Health Sciences
    ClinicalTrials.gov Identifier:
    NCT04696029
    Other Study ID Numbers:
    • BCC016
    First Posted:
    Jan 6, 2021
    Last Update Posted:
    Aug 4, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Medulloblastoma
    Eflornithine

    Study Results

    No Results Posted as of Aug 4, 2022