MRI-Guided Surgery for Glioblastoma
Trial Summary
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor to get a clear answer based on your specific situation.
What data supports the effectiveness of the treatment CEST PH MRI based resection of glioblastoma?
Is MRI-guided surgery for glioblastoma safe?
MRI-guided surgery, including techniques like intraoperative MRI (ioMRI) and preoperative functional MRI (fMRI), has been shown to reduce the risk of complications and improve surgical outcomes in brain tumor surgeries. Studies indicate that using these imaging techniques can lower the chance of functional deterioration after surgery and decrease the rate of adverse events compared to surgeries without these tools.16789
How does the MRI-guided surgery treatment for glioblastoma differ from other treatments?
This treatment uses MRI guidance during surgery to more precisely remove glioblastoma tumors, potentially increasing the amount of tumor removed compared to traditional methods. It allows surgeons to see real-time images of the brain, helping them to avoid healthy tissue and reduce the chance of leaving behind tumor cells.18101112
What is the purpose of this trial?
Current standard of care therapy and all FDA approved adjuvant therapy for glioblastoma continue to provide less than 12 months of progression free survival (PFS) and less than 24 months of overall survival (OS). There is an extreme need for any novel therapy against glioblastoma that increases progression free survival and overall survival in patients diagnosed with this invasive form of cancer. A significant reason for such a poor prognosis is the infiltrative nature of this tumor in non-enhancing regions (NE) beyond the central contrast-enhancing (CE) portion of tumor, which is difficult to visualize and treat with surgical, medical, or radiotherapeutic means.Since tumor cells exhibit abnormal metabolic behavior leading to extracellular acidification, we theorize a newly developed pH-sensitive MRI technique called amine chemical exchange saturation transfer echoplanar imaging (CEST-EPI) may identify infiltrating NE tumor beyond what is clear on standard MRI with gadolinium contrast. This phase I safety study will use use intraoperative CEST-EPI guided resections in glioblastoma at increasing distances from areas of CE tumor to test whether this technique is safe and can remove additional areas of infiltrative NE tumor.The primary objective of this study is to assess the safety of pH-sensitive amine CEST-EPI guided resections for glioblastoma.The secondary objectives of this study include:1. A preliminary efficacy analysis of CEST-EPI guided resections in extending progression free and overall survival.2. To confirm that resected tissue obtained from pH-sensitive amine CEST-EPI guided resections contain infiltrating NE tumor.The primary endpoint for this study will be safety of resecting "CEST positive", acidic regions within T2 hyperintense regions of glioblastoma thought to contain active NE tumor at increasing distances from contrast enhancing tumor with development of a recommended maximal tolerated resection.1. At the maximal tolerated resection, a preliminary efficacy study with endpoints of progression free survival (as defined by RANO Resect 2.0) 1 and overall survival.2. Quantitation of infilitrating tumor burden on CEST-EPI resected tissue using immunohistochemical staining.12 patients up to 24 patients based on resection limiting toxicities with potential expansion of up to 16 patients at the maximum tolerated resection.Inclusion Criteria:1. Must be able to provide written informed consent2. Male or female \> 18 years of age3. Karnofsky Performance Scale (KPS) \> 70 (indicating good performance status).4. Individuals with suspected, newly diagnosed or recurrent IDH wild type WHO IV glioblastoma (intraxial, expansile contrast-enhancing mass without evidence of metastatic disease. This will be reviewed by UCLA neuroradiology to only include patients with high likelihood of GBM)Exclusion Criteria:1. Pediatric patients2. Diagnostic uncertainty (reviewed by UCLA neuroradiology history extracranial malignancy or autoimmune disease)3. Medical conditions that make patients a poor candidate for anesthesia and/or surgery (decision for surgery will follow standard pre-operative clearance guidelines and will not differ for this specific study from standard of care treatment plan)4. Involvement of eloquent areas (as defined by MRI signal clearly involving areas that would lead to a qualifying neurologic deficit as defined in surgical limiting toxicity - this will specifically include: 1) primary motor cortex, 2) primary sensory cortex, 3) sensorimotor fibers as defined on pre-operative diffusion tensor imaging, 4) primary language areas (Broca, Wernicke), 5) arcuate fasiculus as defined on pre-operative diffusion tensor imaging Pre-operative: Standard of care pre-operative MRI including perfusion and pH-weighted amine CEST-EPI (which will add up to 15 minutes of scan time) for a single pre-operative exam prior to surgery.Surgery: 1 day (subjects to be admitted to the hospital) Follow-up: inpatient stay (1-3 days), 2 week clinical assessment (outpatient post-op clinic visit). MRI and clinical assessment at 4 weeks (end of resection limited toxicity window). Following this, there will be standard of care follow up with MRI and clinical assessment starting at 8 weeks +/- 4 weeks (per RANO 2.0). 1Total study duration for recruitment, enrollment, and study completion of all subjects is up to 2 years.Single-arm, surgical resection escalation safety trial with a preliminary efficacy study at the maximal tolerated resectionThis safety evaluation will mimic a phase 1 dose escalation safety study using a rule based approach on based on a i3+3 design.2 Using standard of care resection of contrast enhancement as the baseline, we will begin with 3 subjects with maximal resection + "CEST positive" areas 0.7 cm from the contrast enhancing boundary within areas of T2 hyperintensity. If there is not \> 1 pre-determined resection limiting toxicity (RLT, defined below) in this cohort, the r
Eligibility Criteria
This trial is for individuals with newly diagnosed glioblastoma, a type of brain cancer. Participants must be eligible for standard care and FDA approved therapies. The study aims to include those who can potentially benefit from an advanced MRI technique during surgery.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Pre-operative
Standard pre-operative medical clearance and MRI including gadolinium contrast and CEST-EPI
Surgery
Intraoperative CEST-EPI guided resection of glioblastoma with biopsy and comparison using 5-ALA
Post-operative Follow-up
Immediate post-operative MRI and monitoring for surgical complications
Standard of Care Follow-up
Standard of care follow-up with MRI and clinical assessment starting at 8 weeks
Treatment Details
Interventions
- CEST PH MRI based resection of glioblastoma
Find a Clinic Near You
Who Is Running the Clinical Trial?
University of California, Los Angeles
Lead Sponsor