Superselective Intra-arterial Cerebral Infusion of Temsirolimus in HGG

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.

Study Overview

• Status: Terminated
• Conditions: Glioma; Glioblastoma; High Grade Glioma; Glioma, Malignant
• Intervention / Treatment: Drug: Temsirolimus

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital and Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
• Pregnancy or lactation.
• Known hypersensitivity to temsirolimus or its metabolites, polysorbate 80, or to any other component of temsirolimus.
• Participant has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, active infection, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g. estimated creatinine clearance]
• Received a live vaccination or is in close contact with someone who received a live vaccination within 28 days of the start of study treatment
• Treatment with another investigational drug or other intervention within 30 days prior to the planned treatment Day 1.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single infusion of Temsirolimus; Single infusion of Temsirolimus via super-selective intra-arterial infusion or IV	Drug: Temsirolimus; TORISEL® (temsirolimus) is a kinase inhibitor indicated for the treatment of advanced renal cell carcinoma.; Other Names: Torisel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor pharmacokinetics (PK) of temsirolimus	Total and unbound temsirolimus concentration in tumor tissue.	Day 1 (Intraoperative)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamic effects of temsirolimus	Quantification of the % of pS6 positive cells	Day 1 (Intraoperative)

Collaborators and Investigators

• Sponsor: Nader Sanai
• Collaborators: Barrow Neurological Institute; Ivy Brain Tumor Center
• Investigators: Principal Investigator: Nader Sanai, MD, Chief Scientific Officer/Director

Publications and helpful links

Helpful Links

• Ivy Brain Tumor Center Website

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2023
• Primary Completion (Actual): February 28, 2025
• Study Completion (Actual): October 16, 2025

Study Registration Dates

• First Submitted: March 6, 2023
• First Submitted That Met QC Criteria: March 6, 2023
• First Posted (Actual): March 17, 2023

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Glioma; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antineoplastic; Antineoplastic Agents; Antifungal Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; temsirolimus
• Other Study ID Numbers: 2022-17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No