High Grade GliomaNCT05839379
Targeted Pediatric High-Grade Glioma Therapy
An observational study of High Grade Glioma and Diffuse Intrinsic Pontine Glioma, run by Nationwide Children's Hospital at 22 sites in 7 countries.
Trial summary
The goal of this study is to perform genetic sequencing on brain tumors from children, adolescents, and young adult patients who have been newly diagnosed with a high-grade glioma. Read more about this study
- Who is it for?
- Ages 12 months to 39 years
- Conditions the study is for
- High Grade Glioma, Diffuse Intrinsic Pontine Glioma, Anaplastic Astrocytoma
- How many people
- 350 participants
- Where
- 22 sitesin 7 countries
- Study dates
- 2 Aug 2024to 28 Aug 2034
- Phase
- Observational
- 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 39 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Pediatric and young adult patients new diagnosed with High Grade Glioma including Diffuse Intrinsic Pontine Glioma (per 2021 WHO CNS tumor classification)
Who may be able to join
- Age: Patients must be ≥12 months and ≤39 years of age at the time of enrollment onto this screening protocol.
- Diagnosis: Patients with newly diagnosed HGG, including DIPG are eligible. Diagnosis must have histologic confirmation from biopsy or resection. The diagnosis of HGG must have been confirmed by pathology review at the local site. For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2/3 of the pons, with histopathology consistent with diffuse WHO grade 2-4 glioma (eg, diffuse astrocytoma, anaplastic astrocytoma, glioblastoma, H3K27-altered diffuse midline glioma). For all other tumors, histologic grade must be WHO grade 3-4.
- Disease Status: There are no disease status requirements for enrollment.
- Measurable disease is not required. Patients without measurable disease are eligible.
- Patients with metastatic/disseminated or multifocal disease or gliomatosis cerebri are eligible.
- Patients with a primary spinal tumor are eligible.
Show all 25Show fewer
- Patients with secondary, radiation related HGG are eligible.
- Prior Therapy for HGG: Surgery, radiation, and/or dexamethasone are permissible. Temozolomide concurrent with radiation is permissible. Prior administration of avastin/bevacizumab is allowed (individual treatment arms have different washout period requirements, check individual arm eligibility). No other prior anticancer therapy for HGG will be allowed.
- Participants screening for assignment to TarGeT-L may not have received radiation.
- Timing from surgery to start of RT: For patients who have started RT, radiation must have started <42 days from definitive surgery or biopsy, however it is strongly recommended patients start RT within 31 days from definitive surgery (if patient had two surgeries, radiation must have started within 31 days from second surgery).
- Tumor Sample Availability OR results from previous molecular profiling/targeted sequencing
- If a patient screens through OPTION #1, tumor sample in addition to normal comparator tissue (peripheral blood, saliva, or buccal swab) must be submitted for comprehensive molecular screening at the time of screening enrollment.
- If a patient screens through OPTIONS #2 or #3, results from previously performed molecular profiling must be submitted following enrollment. It is highly recommended that results be uploaded within 7 days of enrollment (if results are available at time of enrollment) or within 7 days of results becoming available (if pending at time of enrollment) to allow adequate time for central review.
- 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.
- Enrollment timeline: Patients are eligible to enroll on the TarGeT-SCR anytime between diagnosis and the following specific timepoints post completion of RT (if relevant)
- Patients screening through OPTION #1 are eligible to enroll anytime between diagnosis and 10 days post RT (if completing RT).
- Patients screening through OPTIONS #2 or #3 are eligible to enroll anytime between diagnosis and 21 days post RT (if completing RT).
- Participants screening for TarGeT-L (lorlatinib) are eligible to enroll on TarGeT-SCR anytime between diagnosis and 31 days post definitive surgery (to allow time for molecular review).
- However, it is important to note the following:
- For treatment protocols that include targeted therapy administered concurrently with RT, patients must start treatment within 10 calendar days of starting RT.
- For treatment protocols that only include maintenance/adjuvant therapy (no systemic therapy given concurrently with radiation), patients must start treatment by 35 days post RT
- #SCREENING OPTIONS
- OPTION1: Molecular screening through CONNECT TarGeT Clinical Testing Laboratories
- OPTION2: Molecular screening through a national comprehensive tumor profiling program
- OPTION3: Clinically validated targeted sequencing or focused profiling
Who cannot join
- -Tumors that do not meet HGG and DIPG diagnoses specified above
Trial locations and contacts
22 sites in 7 countries. Contact the study team or a site near you to ask about taking part.
22 sites in 7 countries
United States12 sites, 12 recruiting
- Recruiting
C.S. Mott Children's Hospital
Ann Arbor, Michigan, 48109
Santhosh Upadhyaya, MD, 866-909-4449, saupadhy@med.umich.edu
- Not yet recruiting
Children's Hospital Colorado
Aurora, Colorado, 80045
Holly Lindsay, MD, 720-777-8314, holly.lindsay@childrenscolorado.org
- Not yet recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Susan C Chi, MD, 6176324386, Susan_chi@dfci.harvard.edu
- Recruiting
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Ashley Plant, MD, 3122274090, Aplant@luriechildrens.org
- Recruiting
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Peter M de Blank, MD, 5135172068, Peter.deBlank@cchmc.org
- Recruiting
Nationwide Children's Hospital
Columbus, Ohio, 43205
Maryam Fouladi, 6147225758, Maryam.fouladi@nationwidechildrens.org
- Recruiting
Duke University Health System
Durham, North Carolina, 27708
Daniel Landi, MD, 19196813824, daniel.landi@duke.edu
- Recruiting
Texas Children's Hospital
Houston, Texas, 77030
Patricia Baxter, MD, 8328244681, pabaxter@txch.org
- Recruiting
University of Miami
Miami, Florida, 33136
Bradley Gampel, MD, 305-243-5302, bxg461@med.miami.edu
- Not yet recruiting
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Michael J Fisher, MD, 12155905188, fisherm@email.chop.edu
- Recruiting
Seattle Children's Hospital
Seattle, Washington, 98105
Erin Crotty, MD, 206-987-2106, erin.crotty@seattlechildrens.org
- Recruiting
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Eugene M Hwang, MD, 2024765046, ehwang@childrensnational.org
Australia4 sites, 4 recruiting
- Recruiting
Royal Children's Hospital
Melbourne, Victoria, 3052
David Eisenstat, MD MA FRCPC FRACP, +61 3 9345 5479, David.Eisenstat@rch.org.au
- Recruiting
Perth Children's Hospital
Perth, Western Australia, 6000
Nick Gottardo, MBChB, FRACP, PhD, +61864560241, nick.gottardo@health.wa.gov.au
- Recruiting
Sydney Children's Hospital
Randwick, New South Wales, 2031
David Ziegler, MBBS, +61293821730, d.ziegler@unsw.edu.au
- Recruiting
Queensland Children's Hospital
South Brisbane, Queensland, 4101
Tim Hassall, MBBS, +61730683593, tim.hassall@health.qld.gov.au
Canada2 sites, 2 recruiting
- Not yet recruiting
Montreal Children's Hospital
Montreal, Quebec, H4A3J1
Genevieve Legault, MD, 5144124400 ext. 60497, Genevieve.legault4@mcgill.ca
- Not yet recruiting
The Hospital for Sick Children (SickKids)
Toronto, Ontario, M5G1X8
Eric Bouffet, MD, 4168137457, eric.bouffet@sickkids.ca
Germany1 site, 1 recruiting
- Not yet recruiting
Hopp Children's Cancer Center at NCT Heidelberg (KiTZ)
Heidelberg, Baden-Wurttemberg, 69120
Olaf Witt, MD, 0496221423570, o.witt@kitz-heidelberg.de
Netherlands1 site, 1 recruiting
- Not yet recruiting
Princess Máxima Center
Utrecht, 3720
Jasper van der Lugt, MD, PhD, 31 6 18559694, J.vanderLugt@prinsesmaximacentrum.nl
New Zealand1 site, 1 recruiting
- Not yet recruiting
Starship Children's Hospital
Auckland, Grafton, 1023
Sarah Hunter, MB ChB, +64 9 367 0000, SHunter@adhb.govt.nz
United Kingdom1 site, 1 recruiting
- Not yet recruiting
Great Ormond Street Hospital
London, WC1N 3JH
Darren Hargrave, MD, 02078138525, darren.hargrave@nhs.net
About this study
Official title: Molecularly-Guided Phase II Umbrella Trial for Children, Adolescents, and Young Adults Newly Diagnosed With High-Grade Glioma, Including Diffuse Intrinsic Pontine Glioma
The goal of this study is to perform genetic sequencing on brain tumors from children, adolescents, and young adult patients who have been newly diagnosed with a high-grade glioma. This molecular profiling will decide if patients are eligible to participate in a subsequent treatment-based clinical trial based on the genetic alterations identified in their tumor.
Read the detailed description
A novel, molecularly-guided, multi-arm phase umbrella II trial is proposed in children, adolescents, and young adults with newly diagnosed HGG, including DIPG, in which we will (1) conduct comprehensive molecular screening of tumor tissue using a multi-omic approach (WES/WGS, gene fusion panels/RNASeq, DNA methylation microarray) across international CONNECT genomics cores with rapid return of clinical results, (2) stratify patients to biologically-targeted treatment arms, based on the tumor molecular profile and histopathology, and (3) perform longitudinal evaluation of peripheral blood, cerebrospinal fluid (CSF), and/or tumor tissue as well as advanced neuro-imaging to determine genomic, immune, and radiologic biomarkers predictive of response, recurrence, resistance, and toxicity.
Based on results of the above tumor molecular profiling and pathology-based confirmation of HGG diagnosis, eligible patients will be assigned to one of several biologically guided treatment arms on a phase II trial.
Approximately 300-350 patients will be enrolled on the screening protocol through which biospecimens (paired tumor DNA/RNA and normal comparator samples) will undergo extensive molecular profiling and/or there will be comprehensive central molecular and pathology review of previously obtained molecular results to assess eligibility to any of the therapeutic subprotocols of the phase II study.
- Conditions
- High Grade Glioma, Diffuse Intrinsic Pontine Glioma, Anaplastic Astrocytoma, Glioblastoma, Glioblastoma Multiforme, Diffuse Midline Glioma, H3 K27M-Mutant
- Medical subject headings
- Glioma, Diffuse Intrinsic Pontine Glioma, Astrocytoma, Glioblastoma, Brain Neoplasms
What is being measured
The primary outcome is the main question the study is designed to answer.
Molecular profiling
Utilize molecular, clinical, and histopathologic data to assess eligibility for specific biologically-guided treatment subprotocols among pediatric, adolescent and young adult patients with newly diagnosed HGG, including DIPG.
Measured: 4 years
Feasibility of molecular profiling and enrollment to a TarGeT treatment protocol
Determine the percent of pediatric, adolescent, and young adult patients newly diagnosed with HGG, including DIPG, who undergo screening through one of three TarGeT-SCR screening mechanisms and are assigned to a TarGeT treatment arm.
Measured: 4 years
Secondary outcomes (7)
Genomic Research
Increase knowledge of the genomic and immunologic landscape of newly-diagnosed pediatric and young adult HGGs, including DIPG, through comprehensive molecular characterization.
Measured: 6 years
Germline susceptibility testing
Determine the frequency and spectrum of germline cancer susceptibility mutations in children and young adults with HGG and DIPG and assess the feasibility of return of those results.
Measured: 4 years
Biobanking
Prospectively collect tumor tissue from diagnostic biopsy/resection as well as baseline peripheral blood and cerebrospinal fluid (CSF) samples for the CONNECT biorepository to be used in correlative research for the present trial as well as future studies.
Measured: 4 years
Progression Free Survival
Prospectively collect data to estimate the distribution of PFS in HGG and DIPG patients, respectively, who do not enroll on any TarGeT treatment subprotocol.
Measured: 4 years
Feasibility of Assignment
Determine the percent of pediatric, adolescent, and young adult patients newly diagnosed with HGG, including DIPG, who are assigned to a TarGeT treatment arm through one of the three TarGeT-SCR screening mechanisms, and begin treatment on a TarGeT treatment subprotocol within the required timelines.
Measured: 4 years
Descriptively analyze patients not assigned
For patients who consent to TarGeT-SCR but do not enroll on a TarGeT treatment subprotocol: Descriptively capture and analyze reasons for lack of treatment arm enrollment.
Measured: 4 years
Overall Survival
Prospectively collect data to estimate the distribution of OS in HGG and DIPG patients, respectively, who do not enroll on any TarGeT treatment subprotocol.
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2023
- Study start2 Aug 2024
- Primary completion28 Aug 2029 (estimated)
- Study completion28 Aug 2034 (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.
- More trials run by Nationwide Children's HospitalThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 350 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nationwide Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Maryam Fouladi, MD, Study chair, Nationwide Children's HospitalMargot Lazow, MD, Study director, Nationwide Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05839379
- Sponsor's protocol ID
- CONNECT TarGeT-SCR
- Other IDs
- R01FD008167, HT9425-23-1-0770
- Status last verified
- Sep 2026
- First submitted
- 20 Apr 2023
- Last updated
- 8 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Molecularly-Guided Phase II Umbrella Trial for Children, Adolescents, and Young Adults Newly Diagnosed With High-Grade Glioma, Including Diffuse Intrinsic Pontine Glioma
- ClinicalTrials.gov ID
- NCT05839379
- Acronym / sponsor ID
- CONNECT TarGeT-SCR
- Conditions
- High Grade Glioma, Diffuse Intrinsic Pontine Glioma, Anaplastic Astrocytoma, Glioblastoma, Glioblastoma Multiforme, Diffuse Midline Glioma, H3 K27M-Mutant
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 350 participants (estimated)
- Lead sponsor
- Nationwide Children's HospitalUniversity, hospital or other
- Study start
- 2 Aug 2024 (actual)
- Primary completion
- 28 Aug 2029 (estimated)
- Study completion
- 28 Aug 2034 (estimated)
- First posted
- 3 May 2023 (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 perform genetic sequencing on brain tumors from children, adolescents, and young adult patients who have been newly diagnosed with a high-grade glioma. This molecular profiling will decide if patients are eligible to participate in a subsequent treatment-based clinical trial based on the genetic alterations identified in their tumor.
Detailed description
A novel, molecularly-guided, multi-arm phase umbrella II trial is proposed in children, adolescents, and young adults with newly diagnosed HGG, including DIPG, in which we will (1) conduct comprehensive molecular screening of tumor tissue using a multi-omic approach (WES/WGS, gene fusion panels/RNASeq, DNA methylation microarray) across international CONNECT genomics cores with rapid return of clinical results, (2) stratify patients to biologically-targeted treatment arms, based on the tumor molecular profile and histopathology, and (3) perform longitudinal evaluation of peripheral blood, cerebrospinal fluid (CSF), and/or tumor tissue as well as advanced neuro-imaging to determine genomic, immune, and radiologic biomarkers predictive of response, recurrence, resistance, and toxicity.
Based on results of the above tumor molecular profiling and pathology-based confirmation of HGG diagnosis, eligible patients will be assigned to one of several biologically guided treatment arms on a phase II trial.
Approximately 300-350 patients will be enrolled on the screening protocol through which biospecimens (paired tumor DNA/RNA and normal comparator samples) will undergo extensive molecular profiling and/or there will be comprehensive central molecular and pathology review of previously obtained molecular results to assess eligibility to any of the therapeutic subprotocols of the phase II study.
Study design
- Observational model
- Other
- Time perspective
- Prospective
Who may qualify
- Ages
- 12 months to 39 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Pediatric and young adult patients new diagnosed with High Grade Glioma including Diffuse Intrinsic Pontine Glioma (per 2021 WHO CNS tumor classification)
Key inclusion criteria (25 listed)
- Age: Patients must be ≥12 months and ≤39 years of age at the time of enrollment onto this screening protocol.
- Diagnosis: Patients with newly diagnosed HGG, including DIPG are eligible. Diagnosis must have histologic confirmation from biopsy or resection. The diagnosis of HGG must have been confirmed by pathology review at the local site. For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2/3 of the pons, with histopathology consistent with diffuse WHO grade 2-4 glioma (eg, diffuse astrocytoma, anaplastic astrocytoma, glioblastoma, H3K27-altered diffuse midline glioma). For all other tumors, histologic grade must be WHO grade 3-4.
- Disease Status: There are no disease status requirements for enrollment.
- Prior Therapy for HGG: Surgery, radiation, and/or dexamethasone are permissible. Temozolomide concurrent with radiation is permissible. Prior administration of avastin/bevacizumab is allowed (individual treatment arms have different washout period requirements, check individual arm eligibility). No other prior anticancer therapy for HGG will be allowed.
- Timing from surgery to start of RT: For patients who have started RT, radiation must have started <42 days from definitive surgery or biopsy, however it is strongly recommended patients start RT within 31 days from definitive surgery (if patient had two surgeries, radiation must have started within 31 days from second surgery).
Key exclusion criteria (1 listed)
- -Tumors that do not meet HGG and DIPG diagnoses specified above
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Molecular profiling
Time frame: 4 years
Utilize molecular, clinical, and histopathologic data to assess eligibility for specific biologically-guided treatment subprotocols among pediatric, adolescent and young adult patients with newly diagnosed HGG, including DIPG.
Feasibility of molecular profiling and enrollment to a TarGeT treatment protocol
Time frame: 4 years
Determine the percent of pediatric, adolescent, and young adult patients newly diagnosed with HGG, including DIPG, who undergo screening through one of three TarGeT-SCR screening mechanisms and are assigned to a TarGeT treatment arm.
7 secondary outcomes
Genomic Research
Time frame: 6 years
Germline susceptibility testing
Time frame: 4 years
Biobanking
Time frame: 4 years
Progression Free Survival
Time frame: 4 years
Feasibility of Assignment
Time frame: 4 years
Descriptively analyze patients not assigned
Time frame: 4 years
Overall Survival
Time frame: 4 years
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 8 Sep 2026.
- Individual participant dataSharing planned: Undecided
Related trials for High Grade Glioma
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A Phase 1 Safety and Dose Finding Study of GLIX1 in Adults With Recurrent or Progressive High-grade Glioma
Glioblastoma Multiforme of Brain, Glioma
RecruitingEarly Phase 1
Intratumoral Extracellular Metabolic Impact of DFMO and AMXT 1501 in Patients With Diffuse or High Grade Glioma
Diffuse Glioma, Malignant Glioma
Active, not recruitingPhase 1
Genetically Modified T-cells in Treating Patients With Recurrent or Refractory Malignant Glioma
Recurrent Glioblastoma, Recurrent Malignant Glioma
Active, not recruitingPhase 1/2
A Study of the Drug Selinexor With Radiation Therapy in Patients With Newly-Diagnosed Diffuse Intrinsic Pontine (DIPG) Glioma and High-Grade Glioma (HGG)
Malignant Glioma
RecruitingPhase 1
Multiple Intracerebral Doses of Neural Stem Cell-Based Virotherapy (NSC-CRAd-S-pk7) for the Treatment of Recurrent High-Grade Gliomas
Currently Only Enrolling Glioblastoma Patients at First Recurrence
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.
Maryam Fouladi, MD study chair
Nationwide Children's Hospital
Margot Lazow, MD study director
Nationwide Children's Hospital
22 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of High Grade Glioma and Diffuse Intrinsic Pontine Glioma, run by Nationwide Children's Hospital at 22 sites in 7 countries.
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 25 inclusion and 1 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: looking for participants now, as of the sponsor's last update on 8 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United States, Australia, Canada, Germany, Netherlands and 2 more countries. 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.
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?
Contact Kelsey H Troyer, PhD (16147223284, kelsey.troyer@nationwidechildrens.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Molecular profiling (time frame: 4 years). The study lists 2 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 8 Sep 2026.