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

Official title

Phase II Glioblastoma Accelerated Biomarkers Learning Environment Trial (GABLE)

Overview

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.

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.

Interventions

• Procedure Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging
  Undergo DSC-MRI
• Other Fluciclovine F18
  Given IV
• Drug Gadolinium-Chelate
  Receive gadolinium-based contrast agent
• Procedure Magnetic Resonance Spectroscopy
  Undergo MR spectroscopy
• Procedure Positron Emission Tomography
  Undergo PET scan

Primary outcome measures

• Overall survival (OS) [Time frame: From biomarker collection to death due to any cause, assessed up to 6 years]
• Event free survival (EFS) [Time frame: From biomarker collection until progression by Neurological Assessment in Neuro-Oncology (NANO) criteria or death, assessed up to 6 years]

Secondary outcome measures (2)

• True disease progression and pseudo-progression (PsP) [Time frame: Within 12 weeks post radiation therapy (XRT)]
• Progression-free survival (PFS) [Time frame: From surgery to the earlier of progression or death due to any cause, assessed up to 6 years]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

United States · 12 centers

• Cedars-Sinai Medical Center — Los Angeles
• Baptist MD Anderson Cancer Center — Jacksonville
• Moffitt Cancer Center — Tampa
• University of Michigan Rogel Cancer Center — Ann Arbor
• Carolinas Medical Center/Levine Cancer Institute — Charlotte
• Duke University Medical Center — Durham
• Wake Forest University Health Sciences — Winston-Salem
• Rhode Island Hospital — Providence
• … and 4 more centers

Identifiers

NCT: NCT06319027 · EAF223 · NCI-2023-08557 · EAF223 · EAF223 · U10CA180820

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗