Phase II Trial of Eflornithine/DFMO as Maintenance Therapy for Molecular High Risk/Very High Risk and Relapsed/Refractory Medulloblastoma
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Giselle Sholler
- Enrollment
- 118
- Locations
- 24
- Primary Endpoint
- Number of participants with event free survival (EFS) during study
Overview
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.
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
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- — to 21 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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)
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.
Arms & Interventions
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.
Intervention: Difluoromethylornithine (Drug)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Determine the Overall Response Rate (ORR) of Participants using Modified RANO Criteria(2 years)
- Determine amount of DFMO in the CSF at 3 hours post dose(2 years)
- Length of time that participants experience Overall Survival (OS)(7 years)
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability(2 years plus 30 days)
Investigators
Giselle Sholler
Beat Childhood Cancer Chair
Milton S. Hershey Medical Center