search
Back to results

Superselective Intra-arterial Cerebral Infusion of Temsirolimus in HGG

Primary Purpose

High Grade Glioma, Glioma, Glioma, Malignant

Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Temsirolimus
Sponsored by
Nader Sanai
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for High Grade Glioma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • St. Joseph's Hospital and Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single infusion of Temsirolimus

Arm Description

Single infusion of Temsirolimus via super-selective intra-arterial infusion or IV

Outcomes

Primary Outcome Measures

Tumor pharmacokinetics (PK) of temsirolimus
Total and unbound temsirolimus concentration in tumor tissue.

Secondary Outcome Measures

Pharmacodynamic effects of temsirolimus
Quantification of the % of pS6 positive cells

Full Information

First Posted
March 6, 2023
Last Updated
May 15, 2023
Sponsor
Nader Sanai
Collaborators
Barrow Neurological Institute, Ivy Brain Tumor Center
search

1. Study Identification

Unique Protocol Identification Number
NCT05773326
Brief Title
Superselective Intra-arterial Cerebral Infusion of Temsirolimus in HGG
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 15, 2023 (Actual)
Primary Completion Date
April 30, 2024 (Anticipated)
Study Completion Date
April 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Nader Sanai
Collaborators
Barrow Neurological Institute, Ivy Brain Tumor Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
High Grade Glioma, Glioma, Glioma, Malignant, Glioblastoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Single infusion of Temsirolimus
Arm Type
Experimental
Arm Description
Single infusion of Temsirolimus via super-selective intra-arterial infusion or IV
Intervention Type
Drug
Intervention Name(s)
Temsirolimus
Other Intervention Name(s)
Torisel
Intervention Description
TORISEL® (temsirolimus) is a kinase inhibitor indicated for the treatment of advanced renal cell carcinoma.
Primary Outcome Measure Information:
Title
Tumor pharmacokinetics (PK) of temsirolimus
Description
Total and unbound temsirolimus concentration in tumor tissue.
Time Frame
Day 1 (Intraoperative)
Secondary Outcome Measure Information:
Title
Pharmacodynamic effects of temsirolimus
Description
Quantification of the % of pS6 positive cells
Time Frame
Day 1 (Intraoperative)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Phase 0 Navigator
Phone
602-406-8605
Email
research@ivybraintumorcenter.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nader Sanai, MD
Organizational Affiliation
Chief Scientific Officer/Director
Official's Role
Principal Investigator
Facility Information:
Facility Name
St. Joseph's Hospital and Medical Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Phase 0 Navigator
Phone
602-406-8605
Email
research@ivybraintumorcenter.org
First Name & Middle Initial & Last Name & Degree
Nader Sanai, MD

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Links:
URL
http://ivybraintumorcenter.org
Description
Ivy Brain Tumor Center Website

Learn more about this trial

Superselective Intra-arterial Cerebral Infusion of Temsirolimus in HGG

We'll reach out to this number within 24 hrs