A Combination Therapy Trial Using an Adaptive Platform Design for Children and Young Adults With Diffuse Midline Gliomas (DMGs) Including Diffuse Intrinsic Pontine Gliomas (DIPGs) at Initial Diagnosis, Post-Radiation Therapy and at Time of Progression
University of California, San Francisco
Summary
This phase II trial determines if the combination of ONC201 with different drugs is effective for treating participants with diffuse midline gliomas (DMGs). Despite years of research, little to no progress has been made to improve outcomes for participants with DMGs, and there are few treatment options. This trial will utilize an adaptive platform design in that the different treatment arms for each cohort will be opened and closed based on ongoing preclinical investigation as well as evolving outcome data from the trial. Novel agents will be continuously added to this study as pre-clinical data emerge to suggest additive or synergistic activity when combined ONC201. Should a novel agent not have an RP2D at the time of incorporation into this study, a phase 1 lead-in will be performed prior to initiation of combination therapy (via study amendment).
Description
OUTLINE: This is a multi-arm/cohort, multi-institutional, open-label trial. The study is divided into cohorts based on stage of disease (newly-diagnosed, post-radiation therapy without disease progression, and at disease progression). ---THIS STUDY IS NOT ENROLLING ON COHORTS 1, 2, AND 3 -- ENROLLING: * Cohort 4: Participants in Cohort 4 will be treated with escalating doses of ONC201 based on evolving pharmacokinetic (PK) data available for ONC201. * Cohort 5: Participants in Cohort 5 will be treated with escalating doses of ONC201 based on evolving PK data and in combination with targete…
Eligibility
- Age range
- 2–39 years
- Sex
- All
- Healthy volunteers
- No
--COHORTS 1, 2, AND 3 CLOSED--- INCLUSION CRITERIA: COHORT 1A AND 1B: * New diagnosis of DMG with imaging and/or pathology consistent with a DMG, including spinal cord tumors. In cohort 1B, previous tumor tissue confirmation of DMG is mandatory and pathology must be consistent with a DMG including diffuse midline glioma Histone 3 lysine 27 - mutant (H3K27M); World Health Organization (WHO) grade III and IV H3 wildtype gliomas. * Must be within 6 weeks of diagnosis to begin standard of care radiation therapy on study. COHORT 2A AND 2B: * Diagnosis of DMG with imaging and/or pathology consi…
Interventions
- DrugONC201
Given orally (PO)
- RadiationRadiation Therapy
Undergo radiation therapy
- DrugPaxalisib
Given PO
- DrugDNX-2401
DNX-2401 is an oncolytic adenovirus that will be administered through direct intratumoral infusion of DNX-2401 via a specialized Neuro Ventricular Cannula.
Locations (32)
- University of Alabama at BirminghamBirmingham, Alabama
- Children's Hospital Los AngelesLos Angeles, California
- University of California, San Diego / Rady Children's Hospital, San DiegoSan Diego, California
- University of California, San FranciscoSan Francisco, California
- Children's National HospitalWashington D.C., District of Columbia
- Ann & Robert H. Lurie Children's Hospital of ChicagoChicago, Illinois