A Phase 1b Study of PTC596 in Children With Newly Diagnosed Diffuse Intrinsic Pontine Glioma and High Grade Glioma
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT03605550 |
Recruitment Status :
Recruiting
First Posted : July 30, 2018
Last Update Posted : September 13, 2022
|
Tracking Information | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|
First Submitted Date ICMJE | July 20, 2018 | |||||||||
First Posted Date ICMJE | July 30, 2018 | |||||||||
Last Update Posted Date | September 13, 2022 | |||||||||
Actual Study Start Date ICMJE | August 1, 2018 | |||||||||
Estimated Primary Completion Date | July 1, 2023 (Final data collection date for primary outcome measure) | |||||||||
Current Primary Outcome Measures ICMJE |
|
|||||||||
Original Primary Outcome Measures ICMJE | Same as current | |||||||||
Change History | ||||||||||
Current Secondary Outcome Measures ICMJE |
|
|||||||||
Original Secondary Outcome Measures ICMJE | Same as current | |||||||||
Current Other Pre-specified Outcome Measures | Not Provided | |||||||||
Original Other Pre-specified Outcome Measures | Not Provided | |||||||||
Descriptive Information | ||||||||||
Brief Title ICMJE | A Phase 1b Study of PTC596 in Children With Newly Diagnosed Diffuse Intrinsic Pontine Glioma and High Grade Glioma | |||||||||
Official Title ICMJE | A Phase 1b Study of PTC596 in Children With Newly Diagnosed Diffuse Intrinsic Pontine Glioma and High Grade Glioma | |||||||||
Brief Summary | In this research study the investigators want to learn more about the safety of the study drug, PTC596 has when taken during radiation. The investigators also want to learn about the effects, if any, these drugs have on children and young adults with brain tumors. The investigators are asking people to be in this research study who have been diagnosed with a high grade glioma (HGG) including diffuse intrinsic pontine glioma (DIPG) to be in the research, because they have scheduled to have radiation to treat their cancer. The study is divided into two parts. The goal of the first part is to find the dose of PTC596 that can be given with radiation without causing serious side effects. The purpose of this surgical study is to test the amount of a study drug that may be found in the tumor and blood when given prior to and during a planned surgery for removal of the recurrent tumor. The goals of the first part:
The goals of the surgical part are:
Funding Source - FDA OOPD |
|||||||||
Detailed Description | This study consists of three parts:
a. newly-diagnosed DIPG who are amenable to undergo biopsy per recommendation of their treating physician OR b. 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. The primary objectives of the Phase I (Part A and Part C) study will be to determine the MTD or RP2D of PTC596 in combination with radiation therapy. Dose-modifying toxicities for maintenance therapy will also be monitored. For Cohorts A and C, PK studies will be collected on Days 1, 2, 3, and 4 (doses 1 and 2) of Cycle 1 and Day 1 of Cycle 2. For Cohort D, plasma PK studies will be collected on Days 1 and 2 of Cycle 1 and Day 1 of Cycle 2. PTC596 will be given twice weekly on Monday and Thursday or Tuesday and Friday, for 6-7 weeks, during daily radiation therapy. Once radiation therapy with concomitant PTC596 is completed, all patients will continue with maintenance therapy which will begin immediately after completion of RT for up to 25 cycles. Once the RP2D has been established, up to 12 patients will be enrolled on the surgical study. Patients eligible for the Surgical Stratum include:
The objectives of the Surgical Cohort Stratum are to:
Patients on the surgical cohort study will commence treatment with the surgical cycle. During the surgical cycle, patients will be treated with two doses of PTC596, on days 1 and 4 of the surgical cycle prior to biopsy or re-resection; the second dose of PTC596 should ideally be administered 3-6 hours before surgery (but may be up to 12 hours prior to surgery). The concentration of PTC596 will then be measured in the tumor and accompanying blood sample by mass spectrometry. BMI-1 expression and the effects of BMI-1 inhibition in DIPG and HGG on gene regulation through gene expression profiling and epigenetic studies will be assessed in tissue and plasma. The PK and PD studies on the surgical cohort study are mandatory. The surgical cycle will end when patients begin RT. Patients must begin RT at least two weeks after the date of surgery and may restart PTC596 on Mondays and Thursdays or Tuesdays and Fridays (twice weekly) after starting RT. Following completion of radiotherapy, patients will immediately start maintenance therapy on a Monday and Thursday or Tuesday and Friday schedule. Patients can continue to receive therapy with PTC596 for up to 25 cycles. |
|||||||||
Study Type ICMJE | Interventional | |||||||||
Study Phase ICMJE | Phase 1 | |||||||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
|||||||||
Condition ICMJE |
|
|||||||||
Intervention ICMJE |
|
|||||||||
Study Arms ICMJE | Experimental: Treatment (PTC596)
PTC596 administered orally twice weekly (M/Th or T/F schedule) concomitantly with radiotherapy. One cycle is defined as 28 days. Post RT patients will continue to receive PTC596 twice weekly for up to 25 cycles.
Interventions:
|
|||||||||
Publications * | Not Provided | |||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
||||||||||
Recruitment Information | ||||||||||
Recruitment Status ICMJE | Recruiting | |||||||||
Estimated Enrollment ICMJE |
64 | |||||||||
Original Estimated Enrollment ICMJE |
30 | |||||||||
Estimated Study Completion Date ICMJE | July 1, 2028 | |||||||||
Estimated Primary Completion Date | July 1, 2023 (Final data collection date for primary outcome measure) | |||||||||
Eligibility Criteria ICMJE | Inclusion Criteria: 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:
|
|||||||||
Sex/Gender ICMJE |
|
|||||||||
Ages ICMJE | 12 Months to 21 Years (Child, Adult) | |||||||||
Accepts Healthy Volunteers ICMJE | No | |||||||||
Contacts ICMJE |
|
|||||||||
Listed Location Countries ICMJE | United States | |||||||||
Removed Location Countries | ||||||||||
Administrative Information | ||||||||||
NCT Number ICMJE | NCT03605550 | |||||||||
Other Study ID Numbers ICMJE | CONNECT1702 5R01FD006352-03 ( U.S. FDA Grant/Contract ) |
|||||||||
Has Data Monitoring Committee | Yes | |||||||||
U.S. FDA-regulated Product |
|
|||||||||
IPD Sharing Statement ICMJE |
|
|||||||||
Current Responsible Party | Nationwide Children's Hospital | |||||||||
Original Responsible Party | Children's Hospital Medical Center, Cincinnati | |||||||||
Current Study Sponsor ICMJE | Nationwide Children's Hospital | |||||||||
Original Study Sponsor ICMJE | Children's Hospital Medical Center, Cincinnati | |||||||||
Collaborators ICMJE | PTC Therapeutics | |||||||||
Investigators ICMJE |
|
|||||||||
PRS Account | Nationwide Children's Hospital | |||||||||
Verification Date | July 2022 | |||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |