Combination Therapy for the Treatment of Diffuse Midline Gliomas

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).

Conditions

• Diffuse Intrinsic Pontine Glioma
• Diffuse Midline Glioma, H3 K27M-Mutant
• Recurrent Diffuse Intrinsic Pontine Glioma
• Recurrent Diffuse Midline Glioma, H3 K27M-Mutant
• Recurrent WHO Grade III Glioma
• WHO Grade III Glioma

Interventions

DRUG

ONC201

Given orally (PO)

RADIATION

Radiation Therapy

Undergo radiation therapy

DRUG

Paxalisib

Given PO

DRUG

DNX-2401

DNX-2401 is an oncolytic adenovirus that will be administered through direct intratumoral infusion of DNX-2401 via a specialized Neuro Ventricular Cannula.

Sponsors & Collaborators

• The Chad-Tough Defeat DIPG Foundation

  collaborator UNKNOWN

• Mithil Prasad Foundation

  collaborator UNKNOWN

• Storm the Heavens Fund

  collaborator UNKNOWN

• National Institute of Neurological Disorders and Stroke (NINDS)

  collaborator NIH

• Jazz Pharmaceuticals

  collaborator INDUSTRY

• Neeve Kolte and Brave Ronil Foundation

  collaborator UNKNOWN

• Will Meeker Foundation

  collaborator UNKNOWN

• CV Biomanufacturing

  collaborator UNKNOWN

• University of California, San Francisco

  lead OTHER

Principal Investigators

• Sabine Mueller, MD, PhD · University of California, San Francisco

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

2 Years

Max Age

39 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-10-20

Primary Completion

2027-12-31

Completion

2029-06-30

FDA Drug

Yes

Countries

• United States
• Australia
• Israel
• Netherlands
• New Zealand
• Switzerland

Study Locations