A Phase 1b Study of PTC596 in Children With Newly Diagnosed Diffuse Intrinsic Pontine Glioma and High Grade Glioma

NCT03605550 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: CONNECT17025R01FD006352-03
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 10

Brief 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). 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

Conditions

High Grade Glioma; Diffuse Intrinsic Pontine Glioma

Keywords

DIPG; High Grade Glioma

Outcome Measures

Primary Outcomes (5)

• 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)

  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.

  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

  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

  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

  Day 4 of surgical cycle

Secondary Outcomes (2)

• Evaluate Overall survival

  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

  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

Study Arms (1)

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

Drug: PTC596; Radiation: Radiotherapy

Interventions

PTC596 DRUG

Oral tablets

Treatment (PTC596)

Radiotherapy RADIATION

Cycle1

Treatment (PTC596)

Eligibility Criteria

• Age: 12 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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:
• 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:

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Nationwide Children's Hospital: lead
• PTC Therapeutics: collaborator

Study Sites (10)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

MeSH Terms

Conditions

Glioma; Diffuse Intrinsic Pontine Glioma

Interventions

PTC596; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Maryam Fouladi, MD

  Nationwide Children's Hospital

  STUDY CHAIR

• Patricia Baxter, MD

  Baylor College of Medicine

  STUDY CHAIR

• Margot Lazow, MD

  Nationwide Children's Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2018
• First Posted: July 30, 2018
• Study Start: August 1, 2018
• Primary Completion: March 1, 2024
• Study Completion (Estimated): March 1, 2029
• Last Updated: March 27, 2026

Record last verified: 2026-03

Locations

US (10)