High Grade GliomaPhase 1NCT03605550
A Phase 1b Study of PTC596 in Children With Newly Diagnosed Diffuse Intrinsic Pontine Glioma and High Grade Glioma
A Phase 1 study testing PTC596 and Radiotherapy in people with High Grade Glioma and Diffuse Intrinsic Pontine Glioma, run by Nationwide Children's Hospital at 10 sites in United States.
Trial summary
The goal of this study is to evaluate the safety of the study drug PTC596 (Unesbulin) taken in combination with radiotherapy (RT) when given to pediatric patients newly diagnosed with High-Grade Glioma (HGG) including diffuse intrinsic pontine glioma (DIPG). Read more about this study
- Who is it for?
- Ages 12 months to 21 years
- Conditions the study is for
- High Grade Glioma, Diffuse Intrinsic Pontine Glioma
- What is being tested?
- PTC596 and Radiotherapy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 10 sitesUnited States
- Study dates
- 1 Aug 2018to 1 Mar 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 months to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age: Patients must be ≥12 months and ≤ 21 years of age at the time of study enrollment.
- Diagnosis: Patients with newly-diagnosed diffuse intrinsic pontine gliomas (DIPGs), defined as tumors with a pontine epicenter and diffuse involvement of at least 2/3 of the pons, are eligible without histologic confirmation.
- Patients with brainstem tumors that do not meet radiographic criteria or are not considered to be typical diffuse intrinsic pontine gliomas will be eligible if the tumors are biopsied and proven to be high-grade gliomas (such as anaplastic astrocytoma, glioblastoma, H3K27-mutant diffuse midline glioma) or diffuse astrocytoma.
- Patients with newly-diagnosed non-brainstem high-grade glioma (HGG) are eligible.
- Patients must have had histologically verified high-grade glioma such as anaplastic astrocytoma, glioblastoma, H3 K27 mutant diffuse midline glioma etc.
- Patients eligible for the surgical stratum include patients with:
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- Newly-diagnosed DIPG who are amenable to undergo biopsy at the recommendation of their treating physician
- Newly-diagnosed HGG for whom a second surgical resection is warranted for further debulking or to achieve a near-total or gross total resection after initial diagnosis has been made but prior to start of therapy.
- Disease Status: Patients with disseminated DIPG or HGG are not eligible, and MRI of spine must be performed if disseminated disease is suspected clinically by the treating physician.
- Performance Level: Karnofsky ≥ 50 for patients > 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
- Neurologic Status: Patients must be able to swallow oral medications to be eligible for study enrollment.
- Patients enrolling on Part A (phase I, capsule formulation) must be able to swallow whole capsules.
- Prior Therapy: Patients must not have received any prior anticancer therapy. Prior dexamethasone and/or surgery are permissible.
- Organ Function Requirements:
- Adequate Bone Marrow Function Defined as:
- Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3
- Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
- Hemoglobin >8 g/dL (may be transfused).
- Adequate Renal Function Defined as:
- Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 or
- A serum creatinine based on age/gender as follows:
- 1 to < 2 years: 0.6 (Male) 0.6 (Female)
- 2 to < 6 years: 0.8 (Male) 0.8 (Female)
- 6 to < 10 years: 1 (Male) 1 (Female)
- 10 to < 13 years: 1.2 (Male) 1.2 (Female)
- 13 to < 16 years: 1.5 (Male) 1.4 (Female)
- 16 years: 1.7 (Male) 1.4 (Female)
- Adequate Liver Function Defined as:
- Total bilirubin must be ≤ 1.5 times institutional upper limit of normal for age
- AST(SGOT)/ALT(SGPT) < 3 times institutional upper limit of normal
- Serum albumin ≥ 2g/dL
- Adequate Cardiac Function Defined As:
- Ejection fraction of ≥ 55% by echocardiogram.
- QTc ≤ 480 msec.
- Adequate Pulmonary Function Defined as
- No evidence of dyspnea at rest, and a pulse oximetry > 94% in room air if there is clinical indication for determination
- Adequate Neurologic Function Defined as:
- Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled.
- Informed Consent: All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
Who cannot join
- Diagnosis: patients with a diagnosis of oligodendroglioma or oligoastrocytoma are not eligible. Patients with juvenile pilocytic astrocytoma, are not eligible.
- Patients with non-brainstem diffuse astrocytoma (grade 2) are not eligible for the HGG stratum of the study.
- Pregnancy or breast-feeding: Pregnant or breast-feeding women will not be entered on this study due to known or unknown risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
- Patients of childbearing or child fathering potential must agree to use adequate contraceptive methods (hormonal or barrier method of birth control; abstinence) while being treated on this study and for 3 months after completing therapy. Note: The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.
- Concomitant Medications
- Corticosteroids: Patients receiving corticosteroids are eligible. The use of corticosteroids must be reported.
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- Investigational Drugs: Patients who are currently receiving another investigational drug are not eligible.
- Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible.
- Anticonvulsants: Patients who are receiving enzyme inducing anticonvulsants as listed in appendix II, are not eligible
- Patients who are receiving rifampin are not eligible.
- Patients who are receiving medications known to prolong QTc interval as listed in appendix III are not eligible.
- Patients who are receiving duloxetine, alosetron or theophylline (CYP1A2 inhibitors) are not eligible
- Patients on beta-blockers are not eligible
- Selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), escitalopram (Lexapro), Fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft) should be used with caution but are not contraindicated.
- Anticoagulants: patients who are receiving therapeutic anticoagulants including warfarin, low-molecular weight heparin are not eligible
- Nasogastric or G tube administration of PTC596 is not permissible.
- Infection: Patients who have an uncontrolled infection are not eligible.
- Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible.
- Patients with evidence of bowel obstruction, malabsorption, or other contraindication to oral medication are not eligible.
- Patients with GI disease or other condition that could affect absorption or predispose subject to gastrointestinal ulceration are not eligible.
- Patients with an active peptic ulcer disease or inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis are not eligible.
- Patients with serious non-healing wounds, ulcers, or bone fractures are not eligible.
- Patients with moderate to severe pulmonary problems generally defined by need for medical intervention (e.g., oxygen, medications) and/or limiting activities of daily living (generally CTCAE Grade 2 or higher) or shortness of breath with limited exertion are not eligible. Pulmonary conditions include (but are not limited to) COPD, asthma, and hemi-pneumectomy.
- Patients with malignancy related to HIV or solid organ transplant: known history of HIV, HBV surface antigen positivity or positive HCV antibody are not eligible. Viral testing is not required unless clinically indicated in patients without a known history.
- Patient with prior or ongoing clinically significant illness, medical or psychiatric condition, medical history, physical findings, ECG findings, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the subject, or alter the absorption, distribution, metabolism, or excretion of the study drugs, or could impair the assessment of study results are not eligible.
- Patients with any prior solid organ transplant are not eligible
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Children's Hospital Colorado
Aurora, Colorado, 80045
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Nationwide Children's Hospital
Columbus, Ohio, 43205
Duke University Medical Center
Durham, North Carolina, 27710
Texas Children's Hospital
Houston, Texas, 77030
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Seattle Children's Hospital
Seattle, Washington, 98105
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
The goal of this study is to evaluate the safety of the study drug PTC596 (Unesbulin) taken in combination with radiotherapy (RT) when given to pediatric patients newly diagnosed with High-Grade Glioma (HGG) including diffuse intrinsic pontine glioma (DIPG).
The main aims of the study are to:
Read more
- Find the safe dose of the study drug PTC596that can be given without causing serious side effects.
- Find out the amount of drug that enters blood (in all patients) and tumor (in patients who receive drug prior to a planned surgery for removal of their brain tumor)
During the first cycle (6-7weeks), patients will receive drug orally twice a week in combination with daily RT. During subsequent cycles (4 weeks each), they will receive only the study drug orally twice a week.
Funding Source - FDA OOPD
Read the detailed description
This study consists of 3 parts:
- The Phase I (Parts A and C), dose-finding component of the trial, to estimate the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of PTC596 in combination with RT followed by maintenance therapy with PTC596, in children with newly-diagnosed DIPG and HGG. Once the RP2D has been determined,
- An early efficacy expansion cohort of up to 17 patients at the RP2D (Part C expansion, and Part D)
- A surgical cohort (part B) of 12 patients with newly diagnosed DIPG who are amenable to undergo biopsy or HGG for whom a second surgical resection is warranted
For patients on cohorts A, C and D, PTC596 will be given orally twice weekly for 6-7 weeks along with daily RT for the first cycle. In subsequent cycles (4 weeks each), all patients will continue with maintenance therapy which will begin immediately after completion of RT for up to 26 cycles (2 years).
For the surgical cohort, patients will be treated with 2 doses of PTC596, on days 1 and 4 prior to biopsy or re-resection; the second dose of PTC596 should ideally be administered 3-6 hrs before surgery. The surgical cycle will end when patients begin RT which should take place at least two weeks after the date of surgery and may restart PTC596 (twice weekly) after starting RT. Following completion of RT, patients will immediately start maintenance therapy with twice weekly PTC596 for up to 26 cycles.
Primary Objectives Parts A, C
- To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of PTC596 given concurrently with radiation in newly-diagnosed patients with DIPG or HGG (Parts A and C)
- To determine the toxicities of PTC596 given concurrently with RT and during maintenance therapy (Parts A, C).
- To characterize the pharmacokinetics of PTC596 given as a capsule and as a tablet in children with newly diagnosed DIPG or HGG when given concurrently with RT and during maintenance (Parts A, C).
Primary Objectives Surgical Cohort -Part B
- To test the ability of PTC596 to inhibit BMI-1 activity in tumor and PBMCs
- To characterize the pharmacokinetics of PTC596 in plasma, cerebrospinal fluid (CSF), and tumor tissue
Secondary Objectives
- To evaluate the overall survival (OS) for newly-diagnosed patients with DIPG treated with PTC596 and compare to historical controls.
- To estimate the progression-free survival (PFS) distribution for newly-diagnosed patients with HGG ttreated with PTC596 and compare to historical controls
- To determine the effects of BMI-1 modulation in DIPG and HGG on BMI-1 levels, H2A monoubiquitination, cell proliferation, cell death, gene regulation, through gene expression profiling and epigenetic studies such as RNA sequencing and ChIP-Seq within the confines of a Phase I study.
- Correlate pre-treatment and post-treatment concentrations of potential biomarkers in biological specimens (e.g., blood and tissue) with response/toxicity, PFS, OS within the confines of a phase I study.
- To examine H3F3A, HIST1H3B (H3.3 and H3.1 genes), ATRX, and DAXX mutations and examine the effects of these alterations using targeted gene, exome, RNA sequencing and methylation arrays of targeted genomic regions in DIPG and HGG.
- To assess the health-related quality-of-life of patients by parent report, and when possible, patient report at key points in therapy using the patient reported outcomes measurement information system (PROMIS) survey.
- To explore tumor volumetric measurements on MRI and correlate with 2-dimensional measurements and compare response criteria.
- To correlate early measures of tumor response (volumetric and 2-dimensional measurements with overall survival.
- Being tested
- PTC596, Radiotherapy
- Keywords
- DIPG, High Grade Glioma
- Medical subject headings
- Glioma, Diffuse Intrinsic Pontine Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PTC596Drug
Oral tablets
RadiotherapyRadiation
Cycle1
| Study group | Role | What they receive |
|---|---|---|
| Treatment (PTC596) | Experimental | PTC596 administered orally twice weekly (M/Th or T/F schedule) concomitantly with RT for 6 -7 weeks. Each subsequent cycle is defined as 28 days. Post RT patients will continue to receive PTC596 twice weekly for up to 26 cycles at RP2D of 200mg/m2 with a maximum dose capped at 400mg for patients with BSA ≥2.0 Receives: Drug: PTC596; Radiation: Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Establish MTD and RP2D of PTC596
To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of PTC596 given concurrently with radiation in newly-diagnosed patients with DIPG or HGG (Parts A and C)
Measured: At the end of Cycle 1 (42-49 days)
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
To determine the toxicities of PTC596 given concurrently with radiotherapy and during maintenance therapy (Parts A, C) in newly diagnosed HGG and DIPG patients treated with PTC596 by calculating the number of participants with, as well as frequency and severity of, PTC596-related Adverse Events as assessed by CTCAE v5.0.
Measured: From Day 1 of treatment through 30 days following end of protocol treatment
Maximum Plasma Concentration [Cmax] of PTC596 (A, B, C, D)
To characterize the plasma pharmacokinetics of PTC596 in children with newly-diagnosed DIPG or HGG when given concurrently with radiotherapy and during maintenance (Parts A, C, D) by measuring the Maximum Concentration [Cmax] and Area Under the Curve (AUC) of PTC596 in plasma
Measured: Days1 through 29
Tumor Concentration of PTC596 (B)
To characterize the pharmacokinetics of PTC596 in tumor tissue of children with newly-diagnosed DIPG and HGG who are treated with PTC596 before undergoing a second resection
Measured: Day 4 of surgical cycle
Protein levels of BMI1 in tumor
To test the ability of PTC596 to inhibit BMI-1 activity and downstream effectors by measuring protein levels in tumor and peripheral blood mononuclear cells (PBMCs) of children with newly-diagnosed HGG and DIPG who are treated with PTC596 before undergoing a second resection
Measured: Day 4 of surgical cycle
Secondary outcomes (2)
Evaluate Overall survival
To estimate the overall survival distribution for newly-diagnosed patients with high-grade glioma treated with PTC596 during radiotherapy followed by PTC596 and compare to historical controls
Measured: From date of treatment until date of death due to any cause or date of last follow-up, assessed up to 60 months
Evaluate Progression Free survival
To estimate the progression-free survival distribution for newly-diagnosed patients with high-grade glioma treated with PTC596 during radiotherapy followed by PTC596 and compare to historical controls
Measured: From date of treatment until date of progressive disease or death due to any cause or date of last follow-up, assessed up to 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2018
- Study start1 Aug 2018
- Primary completion1 Mar 2024
- Study completion1 Mar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for High Grade GliomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 64 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nationwide Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- PTC Therapeutics
- Responsible party
- Sponsor
- Investigators
- Maryam Fouladi, MD, Study chair, Nationwide Children's HospitalPatricia Baxter, MD, Study chair, Baylor College of MedicineMargot Lazow, MD, Study chair, Nationwide Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03605550
- Sponsor's protocol ID
- CONNECT1702
- Other IDs
- 5R01FD006352-03
- Status last verified
- Mar 2026
- First submitted
- 20 Jul 2018
- Last updated
- 27 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: IPD would only be shared following publication of the study.
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Study of PTC596 in Children With Newly Diagnosed Diffuse Intrinsic Pontine Glioma and High Grade Glioma
- ClinicalTrials.gov ID
- NCT03605550
- Acronym / sponsor ID
- CONNECT1702
- Keywords
- DIPG, High Grade Glioma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 64 participants (estimated)
- Lead sponsor
- Nationwide Children's HospitalUniversity, hospital or other
- Collaborators
- PTC Therapeutics
- Study start
- 1 Aug 2018 (actual)
- Primary completion
- 1 Mar 2024 (actual)
- Study completion
- 1 Mar 2029 (estimated)
- First posted
- 30 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this study is to evaluate the safety of the study drug PTC596 (Unesbulin) taken in combination with radiotherapy (RT) when given to pediatric patients newly diagnosed with High-Grade Glioma (HGG) including diffuse intrinsic pontine glioma (DIPG).
The main aims of the study are to:
- Find the safe dose of the study drug PTC596that can be given without causing serious side effects.
- Find out the amount of drug that enters blood (in all patients) and tumor (in patients who receive drug prior to a planned surgery for removal of their brain tumor)
During the first cycle (6-7weeks), patients will receive drug orally twice a week in combination with daily RT. During subsequent cycles (4 weeks each), they will receive only the study drug orally twice a week.
Funding Source - FDA OOPD
Detailed description
This study consists of 3 parts:
- The Phase I (Parts A and C), dose-finding component of the trial, to estimate the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of PTC596 in combination with RT followed by maintenance therapy with PTC596, in children with newly-diagnosed DIPG and HGG. Once the RP2D has been determined,
- An early efficacy expansion cohort of up to 17 patients at the RP2D (Part C expansion, and Part D)
- A surgical cohort (part B) of 12 patients with newly diagnosed DIPG who are amenable to undergo biopsy or HGG for whom a second surgical resection is warranted
For patients on cohorts A, C and D, PTC596 will be given orally twice weekly for 6-7 weeks along with daily RT for the first cycle. In subsequent cycles (4 weeks each), all patients will continue with maintenance therapy which will begin immediately after completion of RT for up to 26 cycles (2 years).
For the surgical cohort, patients will be treated with 2 doses of PTC596, on days 1 and 4 prior to biopsy or re-resection; the second dose of PTC596 should ideally be administered 3-6 hrs before surgery. The surgical cycle will end when patients begin RT which should take place at least two weeks after the date of surgery and may restart PTC596 (twice weekly) after starting RT. Following completion of RT, patients will immediately start maintenance therapy with twice weekly PTC596 for up to 26 cycles.
Primary Objectives Parts A, C
- To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of PTC596 given concurrently with radiation in newly-diagnosed patients with DIPG or HGG (Parts A and C)
- To determine the toxicities of PTC596 given concurrently with RT and during maintenance therapy (Parts A, C).
- To characterize the pharmacokinetics of PTC596 given as a capsule and as a tablet in children with newly diagnosed DIPG or HGG when given concurrently with RT and during maintenance (Parts A, C).
Primary Objectives Surgical Cohort -Part B
- To test the ability of PTC596 to inhibit BMI-1 activity in tumor and PBMCs
- To characterize the pharmacokinetics of PTC596 in plasma, cerebrospinal fluid (CSF), and tumor tissue
Secondary Objectives
- To evaluate the overall survival (OS) for newly-diagnosed patients with DIPG treated with PTC596 and compare to historical controls.
- To estimate the progression-free survival (PFS) distribution for newly-diagnosed patients with HGG ttreated with PTC596 and compare to historical controls
- To determine the effects of BMI-1 modulation in DIPG and HGG on BMI-1 levels, H2A monoubiquitination, cell proliferation, cell death, gene regulation, through gene expression profiling and epigenetic studies such as RNA sequencing and ChIP-Seq within the confines of a Phase I study.
- Correlate pre-treatment and post-treatment concentrations of potential biomarkers in biological specimens (e.g., blood and tissue) with response/toxicity, PFS, OS within the confines of a phase I study.
- To examine H3F3A, HIST1H3B (H3.3 and H3.1 genes), ATRX, and DAXX mutations and examine the effects of these alterations using targeted gene, exome, RNA sequencing and methylation arrays of targeted genomic regions in DIPG and HGG.
- To assess the health-related quality-of-life of patients by parent report, and when possible, patient report at key points in therapy using the patient reported outcomes measurement information system (PROMIS) survey.
- To explore tumor volumetric measurements on MRI and correlate with 2-dimensional measurements and compare response criteria.
- To correlate early measures of tumor response (volumetric and 2-dimensional measurements with overall survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (PTC596) | Experimental | Drug: PTC596, Radiation: RadiotherapyPTC596 administered orally twice weekly (M/Th or T/F schedule) concomitantly with RT for 6 -7 weeks. Each subsequent cycle is defined as 28 days. Post RT patients will continue to receive PTC596 twice weekly for up to 26 cycles at RP2D of 200mg/m2 with a maximum dose capped at 400mg for patients with BSA ≥2.0 |
Who may qualify
- Ages
- 12 months to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (39 listed)
- Age: Patients must be ≥12 months and ≤ 21 years of age at the time of study enrollment.
- Diagnosis: Patients with newly-diagnosed diffuse intrinsic pontine gliomas (DIPGs), defined as tumors with a pontine epicenter and diffuse involvement of at least 2/3 of the pons, are eligible without histologic confirmation.
- Patients with brainstem tumors that do not meet radiographic criteria or are not considered to be typical diffuse intrinsic pontine gliomas will be eligible if the tumors are biopsied and proven to be high-grade gliomas (such as anaplastic astrocytoma, glioblastoma, H3K27-mutant diffuse midline glioma) or diffuse astrocytoma.
- Patients with newly-diagnosed non-brainstem high-grade glioma (HGG) are eligible.
- Patients must have had histologically verified high-grade glioma such as anaplastic astrocytoma, glioblastoma, H3 K27 mutant diffuse midline glioma etc.
Key exclusion criteria (26 listed)
- Diagnosis: patients with a diagnosis of oligodendroglioma or oligoastrocytoma are not eligible. Patients with juvenile pilocytic astrocytoma, are not eligible.
- Patients with non-brainstem diffuse astrocytoma (grade 2) are not eligible for the HGG stratum of the study.
- Pregnancy or breast-feeding: Pregnant or breast-feeding women will not be entered on this study due to known or unknown risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
- Patients of childbearing or child fathering potential must agree to use adequate contraceptive methods (hormonal or barrier method of birth control; abstinence) while being treated on this study and for 3 months after completing therapy. Note: The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.
- Concomitant Medications
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PTC596Oral tablets | Drug | Treatment (PTC596) |
| RadiotherapyCycle1 | Radiation | Treatment (PTC596) |
Primary outcome
Establish MTD and RP2D of PTC596
Time frame: At the end of Cycle 1 (42-49 days)
To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of PTC596 given concurrently with radiation in newly-diagnosed patients with DIPG or HGG (Parts A and C)
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time frame: From Day 1 of treatment through 30 days following end of protocol treatment
To determine the toxicities of PTC596 given concurrently with radiotherapy and during maintenance therapy (Parts A, C) in newly diagnosed HGG and DIPG patients treated with PTC596 by calculating the number of participants with, as well as frequency and severity of, PTC596-related Adverse Events as assessed by CTCAE v5.0.
Maximum Plasma Concentration [Cmax] of PTC596 (A, B, C, D)
Time frame: Days1 through 29
To characterize the plasma pharmacokinetics of PTC596 in children with newly-diagnosed DIPG or HGG when given concurrently with radiotherapy and during maintenance (Parts A, C, D) by measuring the Maximum Concentration [Cmax] and Area Under the Curve (AUC) of PTC596 in plasma
Tumor Concentration of PTC596 (B)
Time frame: Day 4 of surgical cycle
To characterize the pharmacokinetics of PTC596 in tumor tissue of children with newly-diagnosed DIPG and HGG who are treated with PTC596 before undergoing a second resection
Protein levels of BMI1 in tumor
Time frame: Day 4 of surgical cycle
To test the ability of PTC596 to inhibit BMI-1 activity and downstream effectors by measuring protein levels in tumor and peripheral blood mononuclear cells (PBMCs) of children with newly-diagnosed HGG and DIPG who are treated with PTC596 before undergoing a second resection
2 secondary outcomes
Evaluate Overall survival
Time frame: From date of treatment until date of death due to any cause or date of last follow-up, assessed up to 60 months
Evaluate Progression Free survival
Time frame: From date of treatment until date of progressive disease or death due to any cause or date of last follow-up, assessed up to 60 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2026.
- Individual participant dataSharing planned: Undecided. IPD would only be shared following publication of the study.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maryam Fouladi, MD study chair
Nationwide Children's Hospital
Patricia Baxter, MD study chair
Baylor College of Medicine
Margot Lazow, MD study chair
Nationwide Children's Hospital
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PTC596 and Radiotherapy in people with High Grade Glioma and Diffuse Intrinsic Pontine Glioma, run by Nationwide Children's Hospital at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 39 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 27 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Establish MTD and RP2D of PTC596 (time frame: At the end of Cycle 1 (42-49 days)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2026.