This study evaluates whether the addition of FET-PET-guided stereotactic radiosurgery (SRS) to Tumor Treating Fields (TTFields) improves survival outcomes in patients with recurrent IDH-wildtype glioblastoma. Patients with recurrent glioblastoma have limited treatment options and poor prognosis. TTFields is a non-invasive antimitotic therapy that has demonstrated efficacy in recurrent glioblastoma. Stereotactic radiosurgery is commonly used in selected patients with recurrent disease; however, treatment efficacy may be limited by the infiltrative nature of glioblastoma and challenges in accurate target delineation. The study hypothesizes that combining TTFields with FET-PET-guided stereotactic radiosurgery will improve one-year overall survival compared with TTFields alone. Participants will be randomized in a 1:1 ratio to receive either TTFields plus stereotactic radiosurgery or TTFields alone.
Glioblastoma is the most common malignant primary brain tumor in adults and remains associated with poor prognosis despite multimodal treatment. There is currently no established standard therapy for recurrent glioblastoma, and outcomes remain unsatisfactory. Tumor Treating Fields (TTFields) are low-intensity, intermediate-frequency alternating electric fields that disrupt mitosis and inhibit tumor growth. TTFields have demonstrated efficacy in recurrent and newly diagnosed glioblastoma with minimal systemic toxicity. Stereotactic radiosurgery (SRS) is an established local treatment option for selected patients with recurrent glioblastoma. However, MRI-based target delineation may underestimate the true extent of infiltrative tumor growth. FET-PET imaging provides improved visualization of metabolically active tumor tissue and may improve treatment precision. Preclinical studies suggest synergistic effects between TTFields and radiation therapy through increased radiosensitivity and modulation of DNA repair mechanisms. Additional immunomodulatory effects may further enhance treatment efficacy. This prospective randomized single-center study will compare TTFields combined with FET-PET-guided stereotactic radiosurgery versus TTFields alone in patients with recurrent IDH-wildtype glioblastoma. The primary objective is to determine whether combined treatment improves the one-year overall survival rate.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
92
Tumor Treating Fields (TTFields) therapy delivered using alternating electric fields through transducer arrays placed on the scalp. Treatment is administered continuously according to the study protocol for patients with recurrent IDH-wildtype glioblastoma.
Stereotactic radiosurgery planned using MRI and FET-PET imaging for treatment of recurrent IDH-wildtype glioblastoma. Radiosurgery is delivered within 14 days after initiation of TTFields according to protocol-defined target volumes.
Department of Neurooncology and Radiosurgery, Franciszek Lukaszczyk Oncology Center
Bydgoszcz, Poland
RECRUITINGOne-Year Overall Survival Rate
Proportion of participants alive 12 months after randomization
Time frame: 12 months after randomization
Overall Survival (OS)
Overall survival is defined as the time from randomization to death from any cause. Participants who are alive at the time of analysis will be censored at the date of last contact. Median overall survival will be estimated using the Kaplan-Meier method.
Time frame: From randomization until death from any cause, up to 81 months
Progression-Free Survival (PFS)
Progression-free survival is defined as the time from randomization to radiographic disease progression according to RANO 2.0 criteria or death from any cause, whichever occurs first. Participants without an event will be censored at the date of last disease assessment. Median, 6-month, and 12-month progression-free survival rates will be estimated.
Time frame: Up to 12 months after randomization
Objective Response Rate (ORR)
Objective response rate is defined as the proportion of participants achieving a complete response (CR) or partial response (PR) according to RANO 2.0 criteria within 12 months after randomization. Best overall response will be determined using serial MRI assessments.
Time frame: Up to 12 months after randomization
Radiation-Induced Contrast Enhancement (RICE)
Radiation-induced contrast enhancement is defined as new or increasing contrast enhancement observed on follow-up MRI that subsequently remains stable or resolves without evidence of tumor progression. The incidence of radiation-induced contrast enhancement (RICE) will be assessed and compared between study groups.
Time frame: Up to 12 months after randomization
Treatment-Related Adverse Events
Treatment-related adverse events will be assessed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0. The proportion of participants experiencing grade 3 or higher treatment-related adverse events will be compared between treatment groups.
Time frame: From randomization through 12 months after randomization
Patterns of Failure
Patterns of failure will be evaluated based on the location of disease progression relative to the baseline recurrent tumor volume identified on screening MRI and treatment planning imaging. Disease progression will be classified as local, marginal, or distant.
Time frame: Up to 12 months after randomization
Molecular Predictors of overall survival
Associations between molecular tumor characteristics, including MGMT promoter methylation status and other available molecular markers, and treatment outcomes will be evaluated to identify potential predictors of overall survival
Time frame: Up to 81 months after randomization
Corticosteroid Requirements
Corticosteroid requirements will be assessed as the cumulative and daily corticosteroid dose administered from randomization until disease progression. Changes in corticosteroid use over time will be compared between treatment groups.
Time frame: From randomization until disease progression, up to 12 months after randomization
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