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Enzyme Inhibitor

Combination Therapy for Brain Cancer

Phase 2
Recruiting
Led By Sabine Mueller, MD, PhD
Research Sponsored by University of California, San Francisco
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Diarrhea < grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0
No history of congestive heart failure or family history of long QT syndrome.
Must not have
COHORT 1A AND 1B: Thalamic H3K27M DMG.
Evidence of disseminated disease, including diffuse leptomeningeal disease or evidence of CSF dissemination
Timeline
Screening 3 weeks
Treatment Varies
Follow Up 6 months after administration of onc201 in the maintenance phase
Awards & highlights
No Placebo-Only Group

Summary

This trial is testing a combination of three drugs to treat a specific type of brain tumor called diffuse midline gliomas (DMGs). These drugs aim to stop the tumor from growing by blocking enzymes that the cancer cells need. The trial focuses on patients with DMGs because current treatments are not very effective for them.

Who is the study for?
This trial is for patients aged 2 to 39 with diffuse midline gliomas, including those with spinal cord tumors. They must have completed standard radiation therapy and not be pregnant or breastfeeding. Participants need stable vital signs, controlled seizures if present, and agree to use contraception. Those with immune disorders or uncontrolled illnesses are excluded.
What is being tested?
The phase II trial tests ONC201 combined with panobinostat or paxalisib in treating diffuse midline gliomas (DMGs). These drugs inhibit enzymes that may stop tumor growth. The effectiveness of different drug combinations will be assessed for patients who've had little success with other treatments.
What are the potential side effects?
Potential side effects include issues related to enzyme inhibition which could affect cell growth and organ function, as well as typical reactions from cancer therapies such as fatigue, digestive problems, blood-related issues, and increased risk of infection.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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My diarrhea is mild and not severe.
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I have never had heart failure and no family history of long QT syndrome.
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I weigh more than 10 kg, making me eligible for ONC201 treatment.
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My heart is healthy enough for the trial, confirmed by an echocardiogram.
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My blood tests show enough neutrophils and platelets without recent transfusions.
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I don't have shortness of breath at rest, can exercise without lung problems, and my oxygen level is above 92%.
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My heart's electrical activity (QTC) is less than 470 msec.
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My blood sugar is under 125 mg/dL without diabetes medication.
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I am between 2 and 39 years old.
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I have a confirmed diagnosis of recurrent DMG, including spinal cord tumors, and have completed standard radiation therapy.
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My kidney function is normal or only slightly below normal.
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I have DMG, completed standard radiation, and for 2B, confirmed H3K27M or WHO III/IV.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
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My brain tumor is a thalamic H3K27M diffuse midline glioma.
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My cancer has spread to the lining of my brain or spinal cord.
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My diagnosis is a grade II diffuse astrocytoma without H3 mutation.
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I am considered not suitable for a surgical biopsy.
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I have had radiation before for tumor growth.
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I do not have any uncontrolled infections or illnesses.
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I have previously undergone radiation therapy.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~6 months after administration of onc201 in the maintenance phase
This trial's timeline: 3 weeks for screening, Varies for treatment, and 6 months after administration of onc201 in the maintenance phase for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.
Primary study objectives
Number of participants requiring dose modification through first cycle of maintenance (Cohort 5)
Overall survival at 7 months (OS7) - Cohort 3A & 3B Only
Progression-free survival at 6 months (PFS6) - Cohorts 1A, 1B Only
+2 more

Side effects data

From 2021 Phase 2 trial • 30 Patients • NCT03394027
60%
Fatigue
40%
Alkaline phosphatase increased
40%
Aspartate aminotransferase increased
40%
Lymphocyte count decreased
40%
Dizziness
30%
Alanine aminotransferase increased
30%
Diarrhea
20%
Hypophosphatemia
20%
Abdominal pain
20%
Anemia
20%
Nausea
20%
Dyspnea
10%
Edema limbs
10%
Paresthesia
10%
Vaginal discharge
10%
Pain
10%
Sepsis
10%
Lethargy
10%
Vaginal hemorrhage
10%
Proteinuria
10%
Pleural effusion
10%
Flu like symptoms
10%
Gastroesophageal reflux disease
10%
Headache
10%
Atrial flutter
10%
Cardiac arrest
10%
Dehydration
10%
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Death
10%
Sinus tachycardia
10%
Stroke
10%
Thromboembolic event
10%
Urinary tract infection
10%
Anorexia
10%
Arthralgia
10%
Back pain
10%
Constipation
10%
Lymphedema
10%
Malaise
10%
Mucosal infection
10%
Myalgia
10%
Rash maculo-papular
10%
Rhinorrhea
10%
Vascular access complication
10%
Weight loss
10%
Cough
10%
Creatinine increased
100%
80%
60%
40%
20%
0%
Study treatment Arm
Cohort 3-Endometrial Cancer (Female Only)
Cohort 1-Hormone Receptor (HR) + Breast Cancer (Male and Female)
Cohort 2-Triple Negative Breast Cancer (Male and Female)

Awards & Highlights

No Placebo-Only Group
All patients enrolled in this study will receive some form of active treatment.

Trial Design

5Treatment groups
Experimental Treatment
Group I: NOT CURRENTLY ENROLLING - ARM 6: Paxalisib (Day -1), Radiation+Paxalisib , Paxalisib+ONC201Experimental Treatment3 Interventions
Participants may receive a safety lead in of ONC201. During trial validation phase, participants without prior biopsy receive paxalisib PO on day -1 prior to standard of care biopsy. During the radiation/re-irradiation phase, participants without prior radiation therapy or have disease progression after radiation therapy undergo weekly radiation therapy and receive paxalisib PO daily during radiation therapy. During the maintenance phase, participants receive ONC201 PO weekly and paxalisib PO QD. Cycles repeat every 28 days (4 weeks) in the absence of adverse events of unacceptable toxicity
Group II: NOT CURRENTLY ENROLLING - ARM 4: ONC201 (Day -1,-2), Radiation+ONC201, Paxalisib+ONC201Experimental Treatment3 Interventions
Participants may receive a safety lead in of ONC201. During the trial validation phase, participants without prior biopsy receive ONC201 PO on days -2 and -1 prior to standard of care biopsy. During the radiation/re-irradiation phase, participants may receive ONC201 PO weekly during radiation therapy. During the maintenance phase, participants receive ONC201 PO weekly and paxalisib PO QD. Cycles repeat every 28 days (4 weeks) in the absence of adverse events or unacceptable toxicity
Group III: NOT CURRENTLY ENROLLING - ARM 2: ONC201 (Day -1), Radiation+ONC201, Paxalisib+ONC201Experimental Treatment3 Interventions
Participants may receive a safety lead in of ONC201. During the trial validation phase, participants without prior biopsy receive ONC201 PO on day -1 prior to standard of care biopsy. During the radiation/re-irradiation phase, participants without prior radiation therapy or have disease progression after radiation therapy undergo weekly radiation therapy and receive ONC201 PO weekly during radiation therapy. During the maintenance phase, participants receive ONC201 PO weekly and paxalisib PO daily (QD). Cycles repeat every 28 days (4 weeks) in the absence of adverse events of unacceptable toxicity
Group IV: Cohort 5 - ONC201 + Targeted therapiesExperimental Treatment2 Interventions
Participants will receive a starting dose of 625mg of ONC201 weekly on Day 1 and 2 during any non-interventional radiation/re-irradiation per standard of care treatment, and in combination with targeted agents to be selected from approved/available agents based on a rational therapy approach guided by molecular data from the tumor tissue or cerebral spinal fluid (CSF). Each individual targeted agent will be dosed at the recommended therapeutic dose, if a dose has been issued for the participant's age group. Observations and schedule of events will be issued based on the chosen agent determined to best fit the molecular profile (e.g. BRAFV600E, PDGFRA, FGFR1, NF1).
Group V: Cohort 4 - Dose Escalation, Starting Dose 2 (625mg ONC201)Experimental Treatment2 Interventions
Participants will receive a safety lead in of 625mg ONC201. During the trial validation phase, participants without prior biopsy receive ONC201 PO on days -2 and -1 prior to standard of care biopsy. During any non-interventional radiation/re-irradiation per standard of care treatment, participants will receive 625 mg as the starting dose of ONC201 Days 1 and 2 on a weekly basis. Cycles repeat every 28 days (4 weeks) in the absence of adverse events or unacceptable toxicity
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
ONC201
2017
Completed Phase 2
~60
Radiation Therapy
2017
Completed Phase 3
~7250

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.
Mechanism Of Action
Side Effect Profile
Prior Approvals
Other Research
The most common treatments for gliomas, particularly those involving enzyme inhibition, include drugs like ONC201, Panobinostat, and Paxalisib. ONC201 works by targeting the dopamine receptor D2 (DRD2) and ClpP, leading to tumor cell apoptosis. Panobinostat is a histone deacetylase (HDAC) inhibitor that disrupts the function of proteins involved in cancer cell growth and survival. Paxalisib inhibits the PI3K/Akt/mTOR pathway, which is crucial for cell proliferation and survival. These mechanisms are significant for glioma patients as they target specific pathways that are often dysregulated in gliomas, potentially reducing tumor growth and improving patient outcomes.

Find a Location

Who is running the clinical trial?

National Institute of Neurological Disorders and Stroke (NINDS)NIH
1,376 Previous Clinical Trials
651,125 Total Patients Enrolled
University of California, San FranciscoLead Sponsor
2,585 Previous Clinical Trials
15,083,829 Total Patients Enrolled
Mithil Prasad FoundationUNKNOWN
1 Previous Clinical Trials
208 Total Patients Enrolled

Media Library

ONC201 (Enzyme Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT05009992 — Phase 2
Brain Tumor Research Study Groups: NOT CURRENTLY ENROLLING - ARM 2: ONC201 (Day -1), Radiation+ONC201, Paxalisib+ONC201, NOT CURRENTLY ENROLLING - ARM 4: ONC201 (Day -1,-2), Radiation+ONC201, Paxalisib+ONC201, NOT CURRENTLY ENROLLING - ARM 6: Paxalisib (Day -1), Radiation+Paxalisib , Paxalisib+ONC201, Cohort 4 - Dose Escalation, Starting Dose 2 (625mg ONC201), Cohort 5 - ONC201 + Targeted therapies
Brain Tumor Clinical Trial 2023: ONC201 Highlights & Side Effects. Trial Name: NCT05009992 — Phase 2
ONC201 (Enzyme Inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT05009992 — Phase 2
~94 spots leftby Dec 2025