Trial Title:
Targeted Pediatric High-Grade Glioma Therapy
NCT ID:
NCT05839379
Condition:
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
Conditions: Official terms:
Glioblastoma
Glioma
Astrocytoma
Diffuse Intrinsic Pontine Glioma
Study type:
Observational
Overall status:
Recruiting
Study design:
Time perspective:
Prospective
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.
Criteria for eligibility:
Study pop:
Pediatric and young adult patients new diagnosed with High Grade Glioma including Diffuse
Intrinsic Pontine Glioma (per 2021 WHO CNS tumor classification)
Sampling method:
Non-Probability Sample
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
Gender:
All
Minimum age:
12 Months
Maximum age:
39 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Children's Hospital Colorado
Address:
City:
Aurora
Zip:
80045
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Kathleen H Dorris, MD
Phone:
720-777-8314
Email:
kathleen.dorris@childrenscolorado.org
Facility:
Name:
Children's National Medical Center
Address:
City:
Washington
Zip:
20010
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Eugene M Hwang, MD
Phone:
202-476-5046
Email:
ehwang@childrensnational.org
Facility:
Name:
Ann & Robert H. Lurie Children's Hospital of Chicago
Address:
City:
Chicago
Zip:
60611
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Ashley O Plant, MD
Phone:
312-227-4090
Email:
Aplant@luriechildrens.org
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Susan C Chi, MD
Phone:
617-632-4386
Email:
Susan_chi@dfci.harvard.edu
Facility:
Name:
Duke University Health System
Address:
City:
Durham
Zip:
27708
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
David H Ashley, MD
Phone:
919-681-3824
Email:
david.ashley@duke.edu
Facility:
Name:
Cincinnati Children's Hospital Medical Center
Address:
City:
Cincinnati
Zip:
45229
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Peter M de Blank, MD
Phone:
513-517-2068
Email:
Peter.deBlank@cchmc.org
Facility:
Name:
Nationwide Children's Hospital
Address:
City:
Columbus
Zip:
43205
Country:
United States
Status:
Recruiting
Contact:
Last name:
Maryam Fouladi
Phone:
614-722-5758
Email:
Maryam.fouladi@nationwidechildrens.org
Facility:
Name:
Nationwide Children's Hospital
Address:
City:
Columbus
Zip:
43205
Country:
United States
Status:
Recruiting
Contact:
Last name:
Maryam Fouladi, MD, MS, FRCP
Phone:
614-722-5758
Email:
connect@nationwidechildrens.org
Facility:
Name:
Children's Hospital of Philadelphia
Address:
City:
Philadelphia
Zip:
19104
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Michael J Fisher, MD
Phone:
215-590-5188
Email:
fisherm@email.chop.edu
Facility:
Name:
Texas Children's Hospital
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Patricia Baxter, MD
Phone:
832-824-4681
Email:
pabaxter@txch.org
Facility:
Name:
Seattle Children's Hospital
Address:
City:
Seattle
Zip:
98105
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Sarah Leary, MD
Phone:
206-987-2106
Email:
sarah.leary@seattlechildrens.org
Facility:
Name:
Sydney Children's Hospital
Address:
City:
Randwick
Zip:
2031
Country:
Australia
Status:
Not yet recruiting
Contact:
Last name:
David Ziegler, MBBS
Phone:
+61293821730
Email:
d.ziegler@unsw.edu.au
Facility:
Name:
Queensland Children's Hospital
Address:
City:
South Brisbane
Zip:
4101
Country:
Australia
Status:
Not yet recruiting
Contact:
Last name:
Tim Hassall, MBBS
Phone:
+61730683593
Email:
tim.hassall@health.qld.gov.au
Facility:
Name:
Perth Children's Hospital
Address:
City:
Perth
Zip:
6000
Country:
Australia
Status:
Not yet recruiting
Contact:
Last name:
Nick Gottardo, MBChB
Phone:
+61864560241
Email:
nick.gottardo@health.wa.gov.au
Facility:
Name:
The Hospital for Sick Children (SickKids)
Address:
City:
Toronto
Zip:
M5G1X8
Country:
Canada
Status:
Not yet recruiting
Contact:
Last name:
Eric Bouffet, MD
Phone:
4168137457
Email:
eric.bouffet@sickkids.ca
Facility:
Name:
Montreal Children's Hospital
Address:
City:
Montréal
Zip:
H4A3J1
Country:
Canada
Status:
Not yet recruiting
Contact:
Last name:
Genevieve Legault, MD
Phone:
5144124400
Phone ext:
60497
Email:
Genevieve.legault4@mcgill.ca
Facility:
Name:
Hopp Children's Cancer Center at NCT Heidelberg (KiTZ)
Address:
City:
Heidelberg
Zip:
69120
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
Olaf Witt, MD
Phone:
0496221423570
Email:
o.witt@kitz-heidelberg.de
Facility:
Name:
Princess Máxima Center
Address:
City:
Utrecht
Zip:
3720
Country:
Netherlands
Status:
Not yet recruiting
Contact:
Last name:
Jasper van der Lugt, MD, PhD
Phone:
31 6 18559694
Email:
J.vanderLugt@prinsesmaximacentrum.nl
Facility:
Name:
Great Ormond Street Hospital
Address:
City:
London
Zip:
WC1N 3JH
Country:
United Kingdom
Status:
Not yet recruiting
Contact:
Last name:
Darren Hargrave, MD
Phone:
02078138525
Email:
darren.hargrave@nhs.net
Start date:
August 2, 2024
Completion date:
August 28, 2034
Lead sponsor:
Agency:
Nationwide Children's Hospital
Agency class:
Other
Source:
Nationwide Children's Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05839379
