PH Sensitive MRI Based Resections of Glioblastoma

NCT06176066 | Recruiting Phase 1 DMC

• 1 other identifier: 23-001605
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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. 1.A preliminary efficacy analysis of CEST-EPI guided resections in extending progression free and overall survival.
2. 2.To confirm that resected tissue obtained from pH-sensitive amine CEST-EPI guided resections contain infiltrating NE tumor.
3. 3.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.
4. 4.Quantitation of infilitrating tumor burden on CEST-EPI resected tissue using immunohistochemical staining.
5. 5.Must be able to provide written informed consent
6. 6.Male or female \> 18 years of age
7. 7.Karnofsky Performance Scale (KPS) \> 70 (indicating good performance status).
8. 8.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)
9. 9.Pediatric patients
10. 10.Diagnostic uncertainty (reviewed by UCLA neuroradiology history extracranial malignancy or autoimmune disease)
11. 11.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)
12. 12.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.

Conditions

Glioblastoma

Keywords

glioblastoma; magnetic resonance imaging; advanced imaging; surgical oncology

Outcome Measures

Primary Outcomes (1)

• Resection limiting toxicities

  Given the surgical nature of the trial, surgical AEs or RLTs will be pre-determined for monitoring. These will be compared to the standard of care protocols for surgery for glioblastoma. To qualify as a resection limiting toxicity, this must be diagnosed using imaging and/or laboratory analysis and must require intervention (IV antibiotics, repeat surgery). Surgical Events (see full protocol for full details) Infection, hemorrhage, seizure, cerebral edema, hydrocephalus, venous sinus thrombosis, ischemic infarct, unexpected significant qualifying (see full protocol for details) neurological deficit

  2 months

Secondary Outcomes (2)

• Overall survival

  24 months

• Progression Free Survival

  3 months, 6 months, 12 months, 24 months

Study Arms (1)

CEST Resection

EXPERIMENTAL

CEST MRI Based Resection of glioblastoma with standard of care adjuvant therpay (temozolomide + radiation therapy)

Procedure: CEST PH MRI based resection of glioblastoma

Interventions

CEST PH MRI based resection of glioblastoma PROCEDURE

Using pre-operative amine chemical exchange saturation transfer pH weighted MRI, regions of interest that correspond to infiltrating glioblastoma will be identified and via intraoperative neuronavigation, guide resection of glioblastoma

CEST Resection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ≥ 18 years of age.
• Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.
• Karnofsky Performance Scale (KPS) \> 70 (indicating good performance status).
• 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)

You may not qualify if:

• Male or female \< 18 years of age
• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
• Not medically cleared for surgery as defined by standard pre-operative neurosurgery guidelines for open craniotomy for resection (not-biopsy) of tumor.
• 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 diffusion tensor imaging, 4) primary language areas (Broca, Wernicke), 5) arcuate fasiculus as defined on diffusion tensor imaging

Sponsors & Collaborators

• Tower Cancer Research Foundation: collaborator
• University of California, Los Angeles: lead

Study Sites (1)

Ronald Reagan Medical Center

Los Angeles, California, 90095, United States

RECRUITING

Related Publications (2)

• Patel KS, Yao J, Cho NS, Sanvito F, Tessema K, Alvarado A, Dudley L, Rodriguez F, Everson R, Cloughesy TF, Salamon N, Liau LM, Kornblum HI, Ellingson BM. pH-Weighted amine chemical exchange saturation transfer echo planar imaging visualizes infiltrating glioblastoma cells. Neuro Oncol. 2024 Jan 5;26(1):115-126. doi: 10.1093/neuonc/noad150.

  PMID: 37591790 BACKGROUND

• Hagiwara A, Yao J, Raymond C, Cho NS, Everson R, Patel K, Morrow DH, Desousa BR, Mareninov S, Chun S, Nathanson DA, Yong WH, Andrei G, Divakaruni AS, Salamon N, Pope WB, Nghiemphu PL, Liau LM, Cloughesy TF, Ellingson BM. "Aerobic glycolytic imaging" of human gliomas using combined pH-, oxygen-, and perfusion-weighted magnetic resonance imaging. Neuroimage Clin. 2021;32:102882. doi: 10.1016/j.nicl.2021.102882. Epub 2021 Nov 12.

  PMID: 34911188 BACKGROUND

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: The principal investigator is the surgeon and so cannot be blinded from the type of surgical procedure carried out (interventional or standard of care).
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor Department of Neurosurgery

Model Details: Singe center, single arm, Phase 1 surgical dose escalation trial with preliinary effiacy study at the recommended safe maximal resection

Study Record Dates

• First Submitted: December 10, 2023
• First Posted: December 19, 2023
• Study Start: August 5, 2025
• Primary Completion (Estimated): July 1, 2030
• Study Completion (Estimated): July 1, 2030
• Last Updated: May 4, 2026

Record last verified: 2026-04

Locations

US (1)