NCT05009992 · University of California, San Francisco
Combination Therapy for the Treatment of Diffuse Midline Gliomas
(PNOC022)
What this study is about
This phase II trial determines if the combination of ONC201 with different drugs, panobinostat or paxalisib, 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.
View original scientific description
This phase II trial determines if the combination of ONC201 with different drugs, panobinostat or paxalisib, 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. ONC201, panobinostat, and paxalisib are all enzyme inhibitors that may stop the growth of tumor cells by clocking some of the enzymes needed for cell growth.
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.
Primary outcome measures
Progression-free survival at 6 months (PFS6) - Cohorts 1A, 1B Only
Time frame: 6 months after diagnosis
Percentage of participants alive and free from progression at 6 months after the diagnosis. The primary analysis for PFS6 is based on the intention to treat (ITT) population, according to treatment arm assignment. PFS6 is estimated using the Kaplan-Meier method with exact confidence intervals for each cohort and arm. Participants with unknown progression status at 6 months are considered failures (i.e., progressed) for the PFS6 analysis.
Progression-free survival at 6 months (PFS6) - Cohorts 2A, 2B Only
Time frame: 6 months after diagnosis
Percentage of participants alive and free from progression at 6 months after diagnosis. The primary analysis for PFS6 is based on the intention to treat (ITT) population, according to treatment arm assignment. PFS6 is estimated using the Kaplan-Meier method with exact confidence intervals for each cohort and arm. Participants with unknown progression status at 6 months are considered failures (i.e., progressed) for the PFS6 analysis.
Overall survival at 7 months (OS7) - Cohort 3A & 3B Only
Time frame: 7 months after administration of ONC201 in the maintenance phase
OS7 is defined as the percentage of participants alive at 7 months after the initiation of the combination of the backbone (i.e., ONC201) with a novel agent given in the maintenance phase of therapy. The primary analysis for OS7 is based on the ITT population, according to treatment arm assignment. OS7 is estimated using the Kaplan-Meier method with exact confidence intervals for each cohort and arm. Participants with unknown survival status at 7 months are considered failures (i.e., dead) for the OS7 analysis.
Proportion of participants reporting dose-limiting toxicities (DLTs) (Cohort 4)
Time frame: Up through the first cycle of maintenance therapy, approximately 8 months
The safety and tolerability of ONC201 at a previously untested dose will be measured by the proportion of participants reporting a DLT within the first cycle of treatment.
Number of participants requiring dose modification through first cycle of maintenance (Cohort 5)
Time frame: Up through the first cycle of maintenance therapy, approximately 8 months
The safety and tolerability of ONC201 in combination with targeted therapies will be measured by the number of participants reporting dose modification during first cycle.
Maximum tolerated number of intratumor infusions of DNX-2401, with a maximum of 6, in participants with thalamic or pontine DMG who have completed radiotherapy (Cohort 6)
Time frame: A maximum of 6 infusions will be administered every 30 days - approximately 8 months
The safety and tolerability of DNX-2401 at Dose Level 1 (5 × 10\^10 viral particles) will be measured by the proportion of participants reporting a DLT.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- CLOSED TO ENROLLMENT: COHORT 1A AND 1B: (participants with newly diagnosed DMG prior to radiation therapy)
- 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. CLOSED TO ENROLLMENT: : COHORT 2A AND 2B: (participants with DMG who have completed radiation therapy)
- Diagnosis of DMG with imaging and/or pathology consistent with a DMG, including spinal cord tumors, who have complete standard-of-care radiation therapy. In Cohort 2B, previous tumor tissue confirmation of DMG is mandatory and pathology must be consistent with a DMG including diffuse midline glioma H3K27M muta
Where
- Birmingham, Alabama
- Los Angeles, California
- San Diego, California
- San Francisco, California
- Washington D.C., District of Columbia
- Chicago, Illinois
- Indianapolis, Indiana
- Baltimore, Maryland
- Boston, Massachusetts
- Ann Arbor, Michigan
- Minneapolis, Minnesota
- St Louis, Missouri
And 7 more locations — see the full list below.
Collaborators
The Chad-Tough Defeat DIPG Foundation, Mithil Prasad Foundation, Storm the Heavens Fund, National Institute of Neurological Disorders and Stroke (NINDS), Jazz Pharmaceuticals, Neeve Kolte and Brave Ronil Foundation, Will Meeker Foundation, CV Biomanufacturing, Tough2gether Foundation
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jun 26, 2026 · Source of record for eligibility and locations