Identifying Findings on Brain Scans That Could Help Make Better Predictions About Brain Cancer Progression, The GABLE Trial (GABLE)

Phase II Glioblastoma Accelerated Biomarkers Learning Environment Trial (GABLE)

This phase II trial studies whether different imaging techniques can provide additional and more accurate information than the usual approach for assessing the activity of tumors in patients with newly diagnosed glioblastoma. The usual approach for this currently is magnetic resonance imaging (MRI). This study is trying to learn more about the meaning of changes in MRI scans after treatment, as while the appearance of some of these changes may reflect progressing tumor, some may be due the treatment. Dynamic susceptibility contrast (DSC)-MRIs, along with positron emission tomography (PET) and/or magnetic resonance (MR) spectroscopy, may help doctors tell which changes are a reflection of the treatment and which changes may be due to progressing tumor.

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma, IDH-Wildtype
• Intervention / Treatment: Procedure: Positron Emission Tomography; Other: Fluciclovine F18; Procedure: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging; Drug: Gadolinium-Chelate; Procedure: Magnetic Resonance Spectroscopy

Detailed Description

PRIMARY OBJECTIVE:

I. For each biomarker (dynamic susceptibility contrast-enhanced MR Imaging, fluciclovine F18 [18F-fluciclovine] PET, MR spectroscopy), to evaluate whether the biomarker can stratify patients with newly diagnosed glioblastoma (GBM) that have progressive enhancement within 12 weeks post-radiation therapy (XRT) into risk groups based on overall survival.

SECONDARY OBJECTIVES:

I. To evaluate whether each biomarker (dynamic susceptibility contrast-enhanced MR Imaging, 18F-fluciclovine PET, MR spectroscopy) can predict final determination of pseudo-progression (PsP) versus (vs.) true progression on follow-up MR imaging as evaluated by a semi-automated central reading process and by institutional radiologist readings.

II. To evaluate whether a prediction model that incorporates multiple biomarkers can discriminate patients with progressive enhancement within 12 weeks post-XRT into high and low risk groups for overall survival.

III. To evaluate whether clinical and imaging biomarkers are predictive of overall and progression-free survival in patients who do not show progressive enhancement within 12 weeks post-XRT.

EXPLORATORY OBJECTIVE:

I. To determine how different methods of defining PsP vs. true progression on imaging relate to patient survival.

OUTLINE:

Patients receive a gadolinium-based contrast agent and undergo DSC-MRI scans at 4 and 8 weeks after completion of standard of care (SOC) radiation therapy. Patients with evidence of disease progression then undergo MR spectroscopy or receive fluciclovine F18 intravenously (IV) and undergo PET scan within 12 weeks of SOC radiation therapy completion.

After completion of study intervention, patients are followed up every 8 weeks for 1 year followed by every 12 weeks for 5 years.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars-Sinai Medical Center
      • Principal Investigator: Jeremy D. Rudnick
      • Contact: Site Public Contact; Phone Number: 310-423-2133; Email: Cancer.trial.info@cshs.org
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Recruiting
      • Baptist MD Anderson Cancer Center
      • Contact: Site Public Contact; Phone Number: 904-202-7468
      • Principal Investigator: Robert Cavaliere
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
      • Contact: Site Public Contact; Phone Number: 800-679-0775; Email: ClinicalTrials@moffitt.org
      • Principal Investigator: Joaquim Farinhas
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan Rogel Cancer Center
      • Principal Investigator: Michelle M. Kim
      • Contact: Site Public Contact; Phone Number: 800-865-1125; Email: CancerAnswerLine@med.umich.edu
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Recruiting
      • Carolinas Medical Center/Levine Cancer Institute
      • Contact: Site Public Contact; Phone Number: 800-804-9376
      • Principal Investigator: Ashley L. Sumrall
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
      • Contact: Site Public Contact; Phone Number: 888-275-3853
      • Principal Investigator: Annick Desjardins
    • Winston-Salem, North Carolina, United States, 27157
      • Recruiting
      • Wake Forest University Health Sciences
      • Contact: Site Public Contact; Phone Number: 336-713-6771
      • Principal Investigator: Marc Benayoun
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Recruiting
      • Rhode Island Hospital
      • Contact: Site Public Contact; Phone Number: 401-444-1488
      • Principal Investigator: Eric T. Wong
  • West Virginia
    • Huntington, West Virginia, United States, 25701
      • Recruiting
      • Edwards Comprehensive Cancer Center
      • Contact: Site Public Contact; Phone Number: 304-399-6566; Email: Christina.Cole@chhi.org
      • Principal Investigator: Toni O. Pacioles
    • Morgantown, West Virginia, United States, 26506
      • Recruiting
      • West Virginia University Healthcare
      • Contact: Site Public Contact; Phone Number: 304-293-7374; Email: cancertrialsinfo@hsc.wvu.edu
      • Principal Investigator: Sonikpreet Aulakh
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Recruiting
      • University of Wisconsin Carbone Cancer Center - University Hospital
      • Contact: Site Public Contact; Phone Number: 800-622-8922; Email: clinicaltrials@cancer.wisc.edu
      • Principal Investigator: Michael Veronesi
    • Madison, Wisconsin, United States, 53718
      • Recruiting
      • University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
      • Contact: Site Public Contact; Phone Number: 800-622-8922; Email: clinicaltrials@cancer.wisc.edu
      • Principal Investigator: Michael Veronesi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient must be ≥ 18 years of age.
• Patient must have a Karnofsky Performance Status ≥ 60%.
• Patient must have newly diagnosed GBM (must be IDH wild type), with pathologic proof, based on World Health Organization (WHO) 2021 criteria.
• Patient must be planning to receive standard-of-care treatment for newly diagnosed glioblastoma.
• Patient must have completed an MRI prior to the diagnostic surgery for GBM and have images available for upload into Transfer of Images and Data (TRIAD).
• Patient must have diagnostic surgery for GBM within 7 weeks prior to registration.
• Patient must have O6-Methylguanine-DNA Methyltransferase (MGMT) methylation status ordered at time of registration.
• Patient must have a post-operative (op) MRI completed within 3 weeks after diagnostic surgery for GBM and have images available for upload into TRIAD.
• Patient must have no contraindications to MRI, including injection of gadolinium-based contrast agents, and demonstrated ability to tolerate MRI on pre-surgical imaging.
• Patient must have no allergies to agents that may potentially be used for non-standard of care imaging (18F-fluciclovine, MR contrast).

• Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the interventions being used.

  • All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
  • A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
• Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible.
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Diagnostic (DSC-MRI, fluciclovine F18 PET, MR spectroscopy); Patients receive a gadolinium-based contrast agent and undergo DSC-MRI scans at 4 and 8 weeks after completion of SOC radiation therapy. Patients with evidence of disease progression then undergo MR spectroscopy or receive fluciclovine F18 IV and undergo PET scan within 12 weeks of SOC radiation therapy completion.

Procedure: Positron Emission Tomography; Undergo PET scan; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PT; Positron emission tomography (procedure); Other: Fluciclovine F18; Given IV; Other Names: (18F)Fluciclovine; (18F)GE-148; 18F-Fluciclovine; [18F]FACBC; Anti-(18f)FABC; Anti-1-Amino-3-[18F]Fluorocyclobutane-1-Carboxylic Acid; Anti-[18F] FACBC; Axumin; Fluciclovine (18F); FLUCICLOVINE F-18; GE-148 (18F); GE-148 F-18; Procedure: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging; Undergo DSC-MRI; Other Names: DSC-MRI; DSC; Dynamic Susceptibility Contrast-Enhanced MRI; DYNAMIC SUSCEPTIBILITY-CONTRAST MRI; Drug: Gadolinium-Chelate; Receive gadolinium-based contrast agent; Other Names: Gadolinium Coordination Complex; Gadolinium-based Contrast Agent; Gadolinium-Chelant Complex; Procedure: Magnetic Resonance Spectroscopy; Undergo MR spectroscopy; Other Names: NMR Spectroscopy; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; Spectroscopy, MR; Spectroscopy, NMR; Spectroscopy, Nuclear Magnetic Resonance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Will use a two-sided log-rank test to compare the difference in OS between marker positive and marker negative participants using a significance level of 0.05.	From biomarker collection to death due to any cause, assessed up to 6 years
Event free survival (EFS)	NANO progression is defined as a ≥ 2 level worsening from baseline or best level of function in at least one domain or worsening to the highest score within ≥1 domain that is felt to be related to underlying tumor progression and not attributable to a comorbid event or change in concurrent medication. Will be based on the conditional power of a two-sided log-rank test for EFS between marker positive and marker negative participants using a significance level of 0.05.	From biomarker collection until progression by Neurological Assessment in Neuro-Oncology (NANO) criteria or death, assessed up to 6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
True disease progression and pseudo-progression (PsP)	The T3 MRI will be used to determine whether progressive enhancement seen within 12 weeks post-XRT was true progression or PsP.	Within 12 weeks post radiation therapy (XRT)
Progression-free survival (PFS)		From surgery to the earlier of progression or death due to any cause, assessed up to 6 years

Collaborators and Investigators

• Sponsor: ECOG-ACRIN Cancer Research Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Daniel P Barboriak, ECOG-ACRIN Cancer Research Group

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2024
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027

Study Registration Dates

• First Submitted: March 12, 2024
• First Submitted That Met QC Criteria: March 12, 2024
• First Posted (Actual): March 19, 2024

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Investigative Techniques; Chemistry Techniques, Analytical; Spectrum Analysis; Magnetic Resonance Spectroscopy; fluciclovine F-18
• Other Study ID Numbers: EAF223 (Other Identifier: CTEP); U10CA180820 (U.S. NIH Grant/Contract); NCI-2023-08557 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No