## Protocol Section
### Identification Module
**NCT ID:** NCT05839379

**Brief Title:** Targeted Pediatric High-Grade Glioma Therapy

**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

#### Organization Study ID Info
**ID:** TarGeT-SCR
#### Organization
**Class:** OTHER
**Full Name:** Nationwide Children's Hospital
### Status Module
#### Completion Date
**Date:** 2034-05-30

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-14

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-13

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2029-05-30

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05-30

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2023-05-03
**Type:** ACTUAL
**Study First Submit Date:** 2023-04-20
**Study First Submit QC Date:** 2023-05-01
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Nationwide Children's Hospital

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**Brief 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. 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 400-450 patients will be enrolled on the screening protocol through which biospecimens (paired tumor DNA/RNA and normal comparator samples) will undergo extensive molecular profiling to assess eligibility to any of the therapeutic subprotocols of the phase II study.

### Conditions Module

**Conditions:**

- High Grade Glioma

- Diffuse Intrinsic Pontine Glioma

- Anaplastic Astrocytoma

- Glioblastoma

- Glioblastoma Multiforme

- Diffuse Midline Glioma, H3 K27M-Mutant

- Metastatic Brain Tumor

- WHO Grade III Glioma

- WHO Grade IV Glioma

### Design Module

#### Bio Spec

**Description:** Brain tumor samples with matched normal comparator (blood preferred alternatively, saliva or buccal swab)

**Retention:** SAMPLES_WITH_DNA

#### Design Info

**Observational Model:** OTHER

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 450

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Outcomes Module

#### Primary Outcomes

**Description:** 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.

**Measure:** Molecular profiling

**Time Frame:** 4 years

**Description:** Determine the percent of pediatric, adolescent, and young adult patients newly diagnosed with HGG, including DIPG, who undergo comprehensive molecular characterization across clinical molecular testing laboratories at CONNECT sites and begin treatment on a TarGeT treatment subprotocol within 10 calendar days of starting radiation therapy (RT) (if treatment involves an agent given concurrently with RT) or within 35 days of completion of RT (if treatment involves adjuvant maintenance therapy).

**Measure:** Feasibility of molecular profiling and enrollment to a TarGeT treatment protocol

**Time Frame:** 4 years

#### Secondary Outcomes

**Description:** Increase knowledge of the genomic and immunologic landscape of newly-diagnosed pediatric and young adult HGGs, including DIPG, through comprehensive molecular characterization.

**Measure:** Genomic Research

**Time Frame:** 6 years

**Description:** 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.

**Measure:** Germline susceptibility testing

**Time Frame:** 4 years

**Description:** 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.

**Measure:** Biobanking

**Time Frame:** 4 years

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Age: Patients must be ≥12 months and ≤30 years of age at the time of enrollment onto this screening protocol.
2. Diagnosis: Patients with newly diagnosed HGG, including DIPG are eligible. The diagnosis of HGG must have been confirmed by local pathology review. 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.
3. 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.
   * Patients with secondary, radiation related HGG are eligible.
4. Prior Therapy for HGG: Surgery, radiation, and/or dexamethasone are permissible. Temozolomide concurrent with radiation is permissible, but not recommended. 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 within 31 days of definitive surgery or biopsy (if patient had two surgeries, radiation must have started within 31 days from second surgery).
5. 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 or saliva) 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.
6. 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.
7. Enrollment timeline: Patients are eligible to enroll on the TarGeT-SCR anytime between diagnosis and the following specific timepoints post completion of RT

   * Patients screening through OPTION #1 are eligible to enroll anytime between diagnosis and 10 days post RT.
   * Patients screening through OPTIONS #2 or #3 are eligible to enroll anytime between diagnosis and 21 days post RT.

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

Exclusion Criteria:

-Tumors that do not meet HGG and DIPG diagnoses specified above

**Maximum Age:** 39 Years

**Minimum Age:** 12 Months

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- 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)

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** leonie.mikael@nationwidechildrens.org

**Name:** Leonie Mikael, PhD

**Phone:** 16147223284

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Aurora

**Contacts:**

***Contact 1:***

- **Email:** kathleen.dorris@childrenscolorado.org

- **Name:** Kathleen H Dorris, MD

- **Phone:** 720-777-8314

- **Role:** CONTACT

**Country:** United States

**Facility:** Children's Hospital Colorado

**State:** Colorado

**Zip:** 80045

**Location 2:**

**City:** Washington

**Contacts:**

***Contact 1:***

- **Email:** ehwang@childrensnational.org

- **Name:** Eugene M Hwang, MD

- **Phone:** 202-476-5046

- **Role:** CONTACT

**Country:** United States

**Facility:** Children's National Medical Center

**State:** District of Columbia

**Zip:** 20010

**Location 3:**

**City:** Chicago

**Contacts:**

***Contact 1:***

- **Email:** Aplant@luriechildrens.org

- **Name:** Ashley O Plant, MD

- **Phone:** 312-227-4090

- **Role:** CONTACT

**Country:** United States

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

**State:** Illinois

**Zip:** 60611

**Location 4:**

**City:** Boston

**Contacts:**

***Contact 1:***

- **Email:** Susan_chi@dfci.harvard.edu

- **Name:** Susan C Chi, MD

- **Phone:** 617-632-4386

- **Role:** CONTACT

**Country:** United States

**Facility:** Dana-Farber Cancer Institute

**State:** Massachusetts

**Zip:** 02215

**Location 5:**

**City:** Durham

**Contacts:**

***Contact 1:***

- **Email:** david.ashley@duke.edu

- **Name:** David H Ashley, MD

- **Phone:** 919-681-3824

- **Role:** CONTACT

**Country:** United States

**Facility:** Duke University Health System

**State:** North Carolina

**Zip:** 27708

**Location 6:**

**City:** Cincinnati

**Country:** United States

**Facility:** Cincinnati Children's Hospital Medical Center

**State:** Ohio

**Zip:** 45229

**Location 7:**

**City:** Columbus

**Contacts:**

***Contact 1:***

- **Email:** Maryam.fouladi@nationwidechildrens.org

- **Name:** Maryam Fouladi

- **Phone:** 614-722-5758

- **Role:** CONTACT

**Country:** United States

**Facility:** Nationwide Children's Hospital

**State:** Ohio

**Zip:** 43205

**Location 8:**

**City:** Philadelphia

**Contacts:**

***Contact 1:***

- **Email:** fisherm@email.chop.edu

- **Name:** Michael J Fisher, MD

- **Phone:** 215-590-5188

- **Role:** CONTACT

**Country:** United States

**Facility:** Children's Hospital of Philadelphia

**State:** Pennsylvania

**Zip:** 19104

**Location 9:**

**City:** Houston

**Contacts:**

***Contact 1:***

- **Email:** pabaxter@txch.org

- **Name:** Patricia Baxter, MD

- **Phone:** 832-824-4681

- **Role:** CONTACT

**Country:** United States

**Facility:** Texas Children's Hospital

**State:** Texas

**Zip:** 77030

**Location 10:**

**City:** Seattle

**Contacts:**

***Contact 1:***

- **Email:** sarah.leary@seattlechildrens.org

- **Name:** Sarah Leary, MD

- **Phone:** 206-987-2106

- **Role:** CONTACT

**Country:** United States

**Facility:** Seattle Children's Hospital

**State:** Washington

**Zip:** 98105

**Location 11:**

**City:** Randwick

**Contacts:**

***Contact 1:***

- **Email:** d.ziegler@unsw.edu.au

- **Name:** David Ziegler, MBBS

- **Phone:** +61293821730

- **Role:** CONTACT

**Country:** Australia

**Facility:** Sydney Children's Hospital

**State:** New South Wales

**Zip:** 2031

**Location 12:**

**City:** South Brisbane

**Contacts:**

***Contact 1:***

- **Email:** tim.hassall@health.qld.gov.au

- **Name:** Tim Hassall, MBBS

- **Phone:** +61730683593

- **Role:** CONTACT

**Country:** Australia

**Facility:** Queensland Children's Hospital

**State:** Queensland

**Zip:** 4101

**Location 13:**

**City:** Perth

**Contacts:**

***Contact 1:***

- **Email:** nick.gottardo@health.wa.gov.au

- **Name:** Nick Gottardo, MBChB

- **Phone:** +61864560241

- **Role:** CONTACT

**Country:** Australia

**Facility:** Perth Children's Hospital

**State:** Western Australia

**Zip:** 6000

**Location 14:**

**City:** Toronto

**Contacts:**

***Contact 1:***

- **Email:** eric.bouffet@sickkids.ca

- **Name:** Eric Bouffet, MD

- **Phone:** 4168137457

- **Role:** CONTACT

**Country:** Canada

**Facility:** The Hospital for Sick Children (SickKids)

**State:** Ontario

**Zip:** M5G1X8

**Location 15:**

**City:** Montréal

**Contacts:**

***Contact 1:***

- **Email:** Genevieve.legault4@mcgill.ca

- **Name:** Genevieve Legault, MD

- **Phone:** 5144124400

- **Phone Ext:** 60497

- **Role:** CONTACT

**Country:** Canada

**Facility:** Montreal Children's Hospital

**State:** Quebec

**Zip:** H4A3J1

**Location 16:**

**City:** Heidelberg

**Contacts:**

***Contact 1:***

- **Email:** o.witt@kitz-heidelberg.de

- **Name:** Olaf Witt, MD

- **Phone:** 0496221423570

- **Role:** CONTACT

**Country:** Germany

**Facility:** Hopp Children's Cancer Center at NCT Heidelberg (KiTZ)

**State:** Baden-Württemberg

**Zip:** 69120

**Location 17:**

**City:** Utrecht

**Contacts:**

***Contact 1:***

- **Email:** J.vanderLugt@prinsesmaximacentrum.nl

- **Name:** Jasper van der Lugt, MD, PhD

- **Phone:** 31 6 18559694

- **Role:** CONTACT

**Country:** Netherlands

**Facility:** Princess Máxima Center

**Zip:** 3720

**Location 18:**

**City:** London

**Contacts:**

***Contact 1:***

- **Email:** darren.hargrave@nhs.net

- **Name:** Darren Hargrave, MD

- **Phone:** 02078138525

- **Role:** CONTACT

**Country:** United Kingdom

**Facility:** Great Ormond Street Hospital

**Zip:** WC1N 3JH

#### Overall Officials

**Official 1:**

**Affiliation:** Nationwide Children's Hospital

**Name:** Maryam Fouladi, MD

**Role:** STUDY_CHAIR

**Official 2:**

**Affiliation:** Nationwide Children's Hospital

**Name:** Margot Lazow, MD

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**IPD Sharing:** UNDECIDED

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000018302

- Term: Neoplasms, Neuroepithelial

- ID: D000017599

- Term: Neuroectodermal Tumors

- ID: D000009373

- Term: Neoplasms, Germ Cell and Embryonal

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000009375

- Term: Neoplasms, Glandular and Epithelial

- ID: D000009380

- Term: Neoplasms, Nerve Tissue

- ID: D000001932

- Term: Brain Neoplasms

- ID: D000016543

- Term: Central Nervous System Neoplasms

- ID: D000009423

- Term: Nervous System Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000001927

- Term: Brain Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000020295

- Term: Brain Stem Neoplasms

- ID: D000015192

- Term: Infratentorial Neoplasms

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: All

- Name: All Conditions

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M9020

- Name: Glioma

- Relevance: HIGH

- As Found: Glioma

- ID: M9019

- Name: Glioblastoma

- Relevance: HIGH

- As Found: Glioblastoma

- ID: M5209

- Name: Brain Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M2159

- Name: Diffuse Intrinsic Pontine Glioma

- Relevance: HIGH

- As Found: Diffuse Intrinsic Pontine Glioma

- ID: M4561

- Name: Astrocytoma

- Relevance: HIGH

- As Found: Anaplastic Astrocytoma

- ID: M20446

- Name: Neoplasms, Neuroepithelial

- Relevance: LOW

- As Found: Unknown

- ID: M19845

- Name: Neuroectodermal Tumors

- Relevance: LOW

- As Found: Unknown

- ID: M20388

- Name: Neuroectodermal Tumors, Primitive

- Relevance: LOW

- As Found: Unknown

- ID: M12318

- Name: Neoplasms, Germ Cell and Embryonal

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M12320

- Name: Neoplasms, Glandular and Epithelial

- Relevance: LOW

- As Found: Unknown

- ID: M12325

- Name: Neoplasms, Nerve Tissue

- Relevance: LOW

- As Found: Unknown

- ID: M18937

- Name: Central Nervous System Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M12367

- Name: Nervous System Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M5204

- Name: Brain Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M22108

- Name: Brain Stem Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M17898

- Name: Infratentorial Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: T2519

- Name: Glioma

- Relevance: HIGH

- As Found: Glioma

- ID: T2518

- Name: Glioblastoma

- Relevance: HIGH

- As Found: Glioblastoma

- ID: T1865

- Name: Diffuse Intrinsic Pontine Glioma

- Relevance: HIGH

- As Found: Diffuse Intrinsic Pontine Glioma

- ID: T364

- Name: Anaplastic Astrocytoma

- Relevance: HIGH

- As Found: Anaplastic Astrocytoma

- ID: T4092

- Name: Neuroepithelioma

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000005909

- Term: Glioblastoma

- ID: D000005910

- Term: Glioma

- ID: D000001254

- Term: Astrocytoma

- ID: D000080443

- Term: Diffuse Intrinsic Pontine Glioma

### Misc Info Module

- Version Holder: 2024-05-24
