DFMO as Maintenance Therapy for Molecular High/Very High Risk and Relapsed Medulloblastoma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04696029|
Recruitment Status : Recruiting
First Posted : January 6, 2021
Last Update Posted : June 6, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Medulloblastoma||Drug: Difluoromethylornithine||Phase 2|
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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||118 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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 :||March 29, 2021|
|Estimated Primary Completion Date :||March 2028|
|Estimated Study Completion Date :||March 2029|
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).
- 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.
- 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
- 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.
- 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.
- 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||up to 21 Years (Child, Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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).
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04696029
|Contact: Genevieve Bergendahl, MSNfirstname.lastname@example.org|
|United States, Arkansas|
|Arkansas Children's Hospital||Not yet recruiting|
|Little Rock, Arkansas, United States, 72202|
|Contact: Susan Hall 501-364-2760 HallSF@archildrens.org|
|Principal Investigator: Kevin Bielamowicz, MD|
|United States, California|
|UCSF Benioff Children's Hospital Oakland-||Recruiting|
|Oakland, California, United States, 94609|
|Contact: Effie Bourgin EBourgin@mail.cho.org|
|Principal Investigator: Anurag Agrawal, MD|
|United States, Connecticut|
|Connecticut Children's Hospital||Not yet recruiting|
|Hartford, Connecticut, United States, 06106|
|Contact: Amy Newton 860-545-9337 ANewton@connecticutchildrens.org|
|Principal Investigator: Michael Isakoff, MD|
|United States, Florida|
|Arnold Palmer Hospital for Children||Not yet recruiting|
|Orlando, Florida, United States, 32806|
|Contact: Jessica El-Shami 321-841-8588 Jessica.El-Shami@orlandohealth.com|
|Principal Investigator: Amy Smith, MD|
|St. Joseph's Children's Hospital||Recruiting|
|Tampa, Florida, United States, 33607|
|Contact: Jennifer Manns Jennifer.Manns@baycare.org|
|Contact: Connie Nickerson email@example.com|
|Principal Investigator: Don Eslin, MD|
|United States, Kentucky|
|Norton Children's Hospital/University of Louisville||Recruiting|
|Louisville, Kentucky, United States, 40202|
|Contact: Jennifer Thomas Jennifer.Thomas@nortonhealthcare.org|
|Contact: Michael A Huang, MD 502.852.8450 firstname.lastname@example.org|
|Principal Investigator: Huang A Michael, MD|
|United States, Missouri|
|Children's Mercy Hospitals and Clinics||Recruiting|
|Kansas City, Missouri, United States, 64108|
|Contact: Michelle Dinkins 816-302-6893 MDinkins@cmh.edu|
|Principal Investigator: Keith August, MD|
|Cardinal Glennon Children's Medical Center||Not yet recruiting|
|Saint Louis, Missouri, United States, 63104|
|Contact: Katherine Maxwell, RN 314-268-4000|
|Principal Investigator: William Ferguson, MD|
|United States, New Jersey|
|Hackensack University Medical Center||Recruiting|
|Hackensack, New Jersey, United States, 07601|
|Contact: Chreyl Falls Cheryl.Falls@hackensackmeridian.org|
|Principal Investigator: Derek Hanson, MD|
|United States, North Carolina|
|Levine Children's Hospital||Recruiting|
|Charlotte, North Carolina, United States, 28204|
|Contact: Jontyce Green 980-442-2356 email@example.com|
|Principal Investigator: Thomas Russell, MD|
|United States, Pennsylvania|
|Penn State Milton S. Hershey Medical Center and Children's Hospital||Recruiting|
|Hershey, Pennsylvania, United States, 17033|
|Contact: Suzanne Treadway firstname.lastname@example.org|
|Principal Investigator: Valerie Brown, MD|
|United States, South Carolina|
|Medical University of South Carolina||Recruiting|
|Charleston, South Carolina, United States, 29425|
|Contact: Sydney Bargeloh 843-792-2957 BROWNSY@musc.edu|
|Principal Investigator: Jaqueline Kraveka, MD|
|United States, Texas|
|Dell Children's Blood and Cancer Center||Recruiting|
|Austin, Texas, United States, 78723|
|Contact: Rhea Robinson, RN 512-628-1902 TXAUS-DL-SFCHemonc.email@example.com|
|Principal Investigator: Virginia Harrod, MD|
|Study Chair:||Michael A Huang, MD||Beat Childhood Cancer at Atrium Health|
|Responsible Party:||Wake Forest University Health Sciences|
|Other Study ID Numbers:||
|First Posted:||January 6, 2021 Key Record Dates|
|Last Update Posted:||June 6, 2023|
|Last Verified:||June 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neuroectodermal Tumors, Primitive
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Ornithine Decarboxylase Inhibitors
Molecular Mechanisms of Pharmacological Action