A Phase 0, Single-center, Open-label, Dose-escalating Trial Using Super-selective Intra-arterial Infusion of a Single Dose of Temsirolimus for the Treatment of Recurrent High-grade Glioma
This is a single-center, open-label, dose-escalating Phase 0 trial that will enroll participants with a confirmed diagnosed recurrent high-grade glioma (grade 3 or 4 per WHO criteria) targeting the mTOR pathway. Eligible participants will be administered a single infusion of temsirolimus through super-selective intra-arterial infusion or intravenous infusion. Participants will receive the study drug administration on the same day as the planned surgical resection of the tumor.
• Histologically diagnosed high-grade glioma (Grade 3 or 4 per 2021 WHO criteria) in the frontal lobe.
• Tissue must demonstrate mTOR+: PTEN loss OR PIK3C2B or AKT3 amplification on aCGH OR mutations for PIK3CA or PIK3R1, or mTOR or PTEN mutations using next-generation sequencing analysis OR pS6 positivity on immunohistochemistry (≥30% for pS6).
• Patients who have completed the Stupp regimen.
• Have measurable disease pre-operatively, defined as at least 1 contrast enhancing lesion, with 2 perpendicular measurements of at least 1 cm, as per RANO criteria.
• Sufficient biopsy or archival tissue to confirm eligibility
• Has voluntarily agreed to participate by giving written informed consent. Written informed consent for the protocol must be obtained prior to any screening procedures. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness.
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other procedures.
• Age ≥18 at time of consent.
• Have a performance status (PS) of ≤2 on the Eastern Cooperative Oncology (Group (ECOG) scale
• Participant has adequate bone marrow and organ function
• Confirmed negative serum pregnancy test (β-hCG) before starting study treatment or participant who is no longer of childbearing potential due to surgical, chemical, or natural menopause.
• For females of reproductive potential: use of highly effective contraception and agreement to use such a method during study participation until the end of treatment administration and for 3 months after the last dose of study drug.
• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner until the end of treatment administration and for 3 months after the last dose of study drug.
• Agreement to adhere to Lifestyle Considerations throughout study duration