Clinical Trials Logo

Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT05839379
Other study ID # TarGeT-SCR
Secondary ID
Status Not yet recruiting
Phase
First received
Last updated
Start date June 28, 2024
Est. completion date June 28, 2034

Study information

Verified date June 2024
Source Nationwide Children's Hospital
Contact Leonie Mikael, PhD
Phone 16147223284
Email leonie.mikael@nationwidechildrens.org
Is FDA regulated No
Health authority
Study type Observational

Clinical 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. 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.


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.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 450
Est. completion date June 28, 2034
Est. primary completion date June 28, 2029
Accepts healthy volunteers No
Gender All
Age group 12 Months to 39 Years
Eligibility 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

Study Design


Locations

Country Name City State
Australia Perth Children's Hospital Perth Western Australia
Australia Sydney Children's Hospital Randwick New South Wales
Australia Queensland Children's Hospital South Brisbane Queensland
Canada Montreal Children's Hospital Montréal Quebec
Canada The Hospital for Sick Children (SickKids) Toronto Ontario
Germany Hopp Children's Cancer Center at NCT Heidelberg (KiTZ) Heidelberg Baden-Württemberg
Netherlands Princess Máxima Center Utrecht
United Kingdom Great Ormond Street Hospital London
United States Children's Hospital Colorado Aurora Colorado
United States Dana-Farber Cancer Institute Boston Massachusetts
United States Ann & Robert H. Lurie Children's Hospital of Chicago Chicago Illinois
United States Cincinnati Children's Hospital Medical Center Cincinnati Ohio
United States Nationwide Children's Hospital Columbus Ohio
United States Duke University Health System Durham North Carolina
United States Texas Children's Hospital Houston Texas
United States Children's Hospital of Philadelphia Philadelphia Pennsylvania
United States Seattle Children's Hospital Seattle Washington
United States Children's National Medical Center Washington District of Columbia

Sponsors (1)

Lead Sponsor Collaborator
Nationwide Children's Hospital

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Germany,  Netherlands,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. 4 years
Primary 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 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). 4 years
Secondary Genomic Research Increase knowledge of the genomic and immunologic landscape of newly-diagnosed pediatric and young adult HGGs, including DIPG, through comprehensive molecular characterization. 6 years
Secondary 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. 4 years
Secondary 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. 4 years
See also
  Status Clinical Trial Phase
Recruiting NCT05664243 - A Phase 1b / 2 Drug Resistant Immunotherapy With Activated, Gene Modified Allogeneic or Autologous γδ T Cells (DeltEx) in Combination With Maintenance Temozolomide in Subjects With Recurrent or Newly Diagnosed Glioblastoma Phase 1/Phase 2
Completed NCT02768389 - Feasibility Trial of the Modified Atkins Diet and Bevacizumab for Recurrent Glioblastoma Early Phase 1
Recruiting NCT05635734 - Azeliragon and Chemoradiotherapy in Newly Diagnosed Glioblastoma Phase 1/Phase 2
Completed NCT03679754 - Evaluation of Ad-RTS-hIL-12 + Veledimex in Subjects With Recurrent or Progressive Glioblastoma, a Substudy to ATI001-102 Phase 1
Completed NCT01250470 - Vaccine Therapy and Sargramostim in Treating Patients With Malignant Glioma Phase 1
Terminated NCT03927222 - Immunotherapy Targeted Against Cytomegalovirus in Patients With Newly-Diagnosed WHO Grade IV Unmethylated Glioma Phase 2
Recruiting NCT03897491 - PD L 506 for Stereotactic Interstitial Photodynamic Therapy of Newly Diagnosed Supratentorial IDH Wild-type Glioblastoma Phase 2
Active, not recruiting NCT03587038 - OKN-007 in Combination With Adjuvant Temozolomide Chemoradiotherapy for Newly Diagnosed Glioblastoma Phase 1
Completed NCT01922076 - Adavosertib and Local Radiation Therapy in Treating Children With Newly Diagnosed Diffuse Intrinsic Pontine Gliomas Phase 1
Recruiting NCT04391062 - Dose Finding for Intraoperative Photodynamic Therapy of Glioblastoma Phase 2
Active, not recruiting NCT03661723 - Pembrolizumab and Reirradiation in Bevacizumab Naïve and Bevacizumab Resistant Recurrent Glioblastoma Phase 2
Active, not recruiting NCT02655601 - Trial of Newly Diagnosed High Grade Glioma Treated With Concurrent Radiation Therapy, Temozolomide and BMX-001 Phase 2
Completed NCT02206230 - Trial of Hypofractionated Radiation Therapy for Glioblastoma Phase 2
Completed NCT03493932 - Cytokine Microdialysis for Real-Time Immune Monitoring in Glioblastoma Patients Undergoing Checkpoint Blockade Phase 1
Terminated NCT02709889 - Rovalpituzumab Tesirine in Delta-Like Protein 3-Expressing Advanced Solid Tumors Phase 1/Phase 2
Recruiting NCT06058988 - Trastuzumab Deruxtecan (T-DXd) for People With Brain Cancer Phase 2
Completed NCT03018288 - Radiation Therapy Plus Temozolomide and Pembrolizumab With and Without HSPPC-96 in Newly Diagnosed Glioblastoma (GBM) Phase 2
Withdrawn NCT03980249 - Anti-Cancer Effects of Carvedilol With Standard Treatment in Glioblastoma and Response of Peripheral Glioma Circulating Tumor Cells Early Phase 1
Not yet recruiting NCT04552977 - A Trail of Fluzoparil in Combination With Temozolomide in Patients With Recurrent Glioblastoma Phase 2
Terminated NCT02905643 - Discerning Pseudoprogression vs True Tumor Growth in GBMs