Superselective Intra-arterial Cerebral Infusion of Temsirolimus in HGG

Glioblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05773326
• Other study ID #: 2022-17
• Status: Recruiting
• Phase: Early Phase 1
• Start date: May 15, 2023
• Est. completion date: April 30, 2025

Study information

• Verified date: May 2023
• Source: St. Joseph's Hospital and Medical Center, Phoenix
• Contact: Phase 0 Navigator
• Phone: 602-406-8605
• Email: research[@]ivybraintumorcenter.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: April 30, 2025
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (ß-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.

Related Conditions & MeSH terms

• Glioblastoma
• Glioma
• Glioma, Malignant
• High Grade Glioma

Intervention

Drug:
• Temsirolimus
TORISEL® (temsirolimus) is a kinase inhibitor indicated for the treatment of advanced renal cell carcinoma.

Locations

Country	Name	City	State
United States	St. Joseph's Hospital and Medical Center	Phoenix	Arizona

Sponsors (3)

Lead Sponsor	Collaborator
Nader Sanai	Barrow Neurological Institute, Ivy Brain Tumor Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tumor pharmacokinetics (PK) of temsirolimus	Total and unbound temsirolimus concentration in tumor tissue.	Day 1 (Intraoperative)
Secondary	Pharmacodynamic effects of temsirolimus	Quantification of the % of pS6 positive cells	Day 1 (Intraoperative)

External Links

•   Ivy Brain Tumor Center Website