GRETeL: Tumor Response to Standard Radiotherapy and TMZ Patients With GBM

A Study for Patients Newly Diagnosed With Glioblastoma Being Treated With Standard Radiotherapy and Temozolomide (TMZ) to Evaluate Tumor Response Via Liquid Biopsies (GRETeL)

The purpose of this study is to better define longitudinal genomic alterations in patients with glioblastoma (GBM), and to determine if plasma circulating tumor DNA (ctDNA) or cell free DNA (cfDNA) is associated with disease recurrence, survival, tumor characteristics, and/or peripheral immunosuppression.

Study Overview

• Status: Suspended
• Conditions: Glioblastoma; Glioma, Malignant

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • The Preston Robert Tisch Brain Tumor Center at Duke University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients newly diagnosed with glioblastoma post-resection who are scheduled to receive standard radiation and chemotherapy (temozolomide).

Description

Inclusion Criteria:

• Age ≥ 18 years
• Patients newly diagnosed with malignant glioma, IDH wildtype who have undergone surgical resection for their tumor and who are planned for standard of care radiation therapy with concurrent temozolomide (i.e., at least 59 Gy in 30 fractions over 6 weeks)
• Patients must have leftover tissue available from the surgical resection of their tumor available to request for this research.
• Able to undergo MRI of brain with and without contrast
• Signed informed consent approved by the Institutional Review Board (IRB)

Exclusion Criteria:

• Prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Pilot; The first 20 patients accrued to this study will be assayed to validate the performance of the assays developed by Personalis. This pilot sub-study will be analyzed in a "blinded" manner without clinical information.
Full Study; The remaining 80 patients accrued to this study (after the initial 20 patients accrue to the "Pilot" cohort).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median cf/ctDNA concentration at pre- and post-radiation, as well as median change in ct/ctDNA concentration	Identify and describe changes in the cell free DNA (cfDNA) sequencing profiles of patients diagnosed with GBM in pre- versus post-radiation therapy samples, and to assess the association between these changes and clinical outcome, including progression free and overall survival	6 months
Median levels of cfDNA collected longitudinally after completion of radiation	Identify and describe changes over time after radiotherapy in the cfDNA sequencing profiles of patients diagnosed with GBM, and to assess the association between these longitudinal changes in cfDNA and clinical outcome, including progression free and overall survival	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterize the fragmentomic landscape of GBM	Median number of ctDNA fragments obtained from tumor tissue, pre-radiation serum specimen, and post-radiation serum specimen, and healthy controls.	6 months
Spearman correlation between clinical descriptors and measures of ctDNA	Assess the association between degree and frequency of ctDNA shedding and clinical characteristics, such as molecular findings, histopathological characteristics, corticosteroid use, and bevacizumab use.	6 months
Median and range for measures of tumor immune infiltration	Quantify the level of immune infiltration in the tumor, and assess its association with progression-free survival (PFS), overall survival (OS), and ctDNA detection.	6 months
Hazard ratio for the relationship between chromosomal instability and OS or PFS	Assess the prognostic value of chromosomal instability/CAN burden, and assess its association with ctDNA from plasma.	6 months
Spearman correlation between ctDNA and peripheral T cell function, autoantibodies.	Determine if peripheral T cell function and stemness or autoantibodies are association with ctDNA levels, or TME composition.	6 months

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Personalis Inc.
• Investigators: Principal Investigator: Mustafa Khasraw, MBChB, MD, FRCP, FRACP, Duke University

Publications and helpful links

Helpful Links

• Duke Health
• The Preston Robert Tisch Brain Center at Duke University

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2023
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: December 20, 2022
• First Submitted That Met QC Criteria: January 20, 2023
• First Posted (Actual): January 25, 2023

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Glioma; Glioblastoma; Duke; Khasraw; Pro00110247; GRETEL
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Glioma
• Other Study ID Numbers: Pro00110247

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No