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Study of BDTX-1535 in Recurrent High-Grade Glioma (HGG) Participants With EGFR Alterations or Fusions

Primary Purpose

High Grade Glioma

Status
Not yet recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
BDTX-1535
Sponsored by
St. Joseph's Hospital and Medical Center, Phoenix
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: Participants who have had a prior resection of diagnosed HGG (2021 WHO grade 3 and 4), defined as participants who have progressed on or following standard therapy, which includes maximal surgical resection, temozolomide, and fractionated radiotherapy. Adequate archival or biopsy tissue available for testing of EGFR alterations. Participants must have measurable disease preoperatively. Have a performance status (PS) of ≤2 on the Eastern Cooperative Oncology Group (ECOG) scale. Ability to swallow oral medications. Participant has adequate bone marrow and organ function Exclusion Criteria: Pregnancy or breastfeeding. Known allergic reactions to components of the BDTX-1535. Known to have active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and active and chronic hepatitis, as determined by the investigator. Known active systemic bacterial infection, fungal infection, or detectable viral infection . Significant cardiovascular disease. Symptomatic or radiographic leptomeningeal disease. Participant has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study . Concurrent use of prohibited medications.

Sites / Locations

  • St. Joseph's Hospital and Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Recurrent high-grade glioma participants with EGFR alterations

Recurrent high-grade glioma participants with EGFR fusion

Arm Description

Outcomes

Primary Outcome Measures

Unbound concentration of BDTX-1535 in tumor tissue
Unbound BDTX-1535 concentration in Gd-enhancing and Gd-non-enhancing tumor tissue
Total concentration of BDTX-1535 in tumor tissue
Total BDTX-1535 concentration in Gd-enhancing and Gd-non-enhancing tumor tissue
Progression Free Survival (PFS)
Rate of 6-month progression-free survival

Secondary Outcome Measures

Concentration of BDTX-1535 in CSF
BDTX-1535 level in CSF will be determined
Percentage of pEGFR positive cells in tumor tissue
Expression of pEGFR in BDTX-1535 treated HGG tissue compared to archival tissue.
Percentage of pERK positive cells in tumor tissue
Expression of pERK in BDTX-1535 treated HGG tissue compared to archival tissue.
Overall survival (OS)
Median overall survival in participants with demonstrated PK effect
Safety and tolerability - adverse events
Number of adverse events through study completion
Safety and tolerability - death
Number of deaths
Clinical laboratory abnormalities per CTCAE
Incidence of Clinical laboratory abnormalities per CTCAE

Full Information

First Posted
September 25, 2023
Last Updated
October 2, 2023
Sponsor
St. Joseph's Hospital and Medical Center, Phoenix
Collaborators
Ivy Brain Tumor Center, Barrow Neurological Institute
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1. Study Identification

Unique Protocol Identification Number
NCT06072586
Brief Title
Study of BDTX-1535 in Recurrent High-Grade Glioma (HGG) Participants With EGFR Alterations or Fusions
Official Title
A Phase 0/1 Study of BDTX-1535 in Recurrent High-Grade Glioma (HGG) Participants With EGFR Alterations or Fusions Scheduled for Resection to Evaluate Central Nervous System (CNS) Penetration With PK-triggered Expansion Cohort
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 27, 2023 (Anticipated)
Primary Completion Date
May 2025 (Anticipated)
Study Completion Date
October 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
St. Joseph's Hospital and Medical Center, Phoenix
Collaborators
Ivy Brain Tumor Center, Barrow Neurological Institute

4. Oversight

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

5. Study Description

Brief Summary
This study will administer the investigational drug, BDTX-1535 to eligible patients with recurrent high-grade glioma. BDTX-1535 was designed to block a growth signal important to some cancers. BDTX-1535 is being tested in this study to see if it can be given safely to people who have tumors that can be dependent on that growth signal because of changes in a protein called EGFR. These gene changes are called amplifications, mutations, fusions or alterations and are found only in the tumors.
Detailed Description
Eligible participants will enroll in the Phase 0 study and receive BDTX-1535 prior to a planned resection. During surgery, blood, tumor, and CSF samples will be collected to measure the amount of drug that is present in the samples. Participants with tumors demonstrating PK response will continue with once-daily BDTX-1535 treatment, continuously in 28-day cycles after surgery. Participants will continue to receive BDTX-1535 until the progression of disease, unacceptable toxicity or death, withdrawal of consent, loss to follow-up, or study termination by the sponsor.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
22 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Recurrent high-grade glioma participants with EGFR alterations
Arm Type
Experimental
Arm Title
Recurrent high-grade glioma participants with EGFR fusion
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
BDTX-1535
Intervention Description
BDTX-1535 is an inhibitor of EGFR mutations
Primary Outcome Measure Information:
Title
Unbound concentration of BDTX-1535 in tumor tissue
Description
Unbound BDTX-1535 concentration in Gd-enhancing and Gd-non-enhancing tumor tissue
Time Frame
Phase 0 Intraoperative Sample
Title
Total concentration of BDTX-1535 in tumor tissue
Description
Total BDTX-1535 concentration in Gd-enhancing and Gd-non-enhancing tumor tissue
Time Frame
Phase 0 Intraoperative Sample
Title
Progression Free Survival (PFS)
Description
Rate of 6-month progression-free survival
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Concentration of BDTX-1535 in CSF
Description
BDTX-1535 level in CSF will be determined
Time Frame
Phase 0 Intraoperative sample
Title
Percentage of pEGFR positive cells in tumor tissue
Description
Expression of pEGFR in BDTX-1535 treated HGG tissue compared to archival tissue.
Time Frame
Phase 0 Intraoperative Sample
Title
Percentage of pERK positive cells in tumor tissue
Description
Expression of pERK in BDTX-1535 treated HGG tissue compared to archival tissue.
Time Frame
Phase 0 Intraoperative Sample
Title
Overall survival (OS)
Description
Median overall survival in participants with demonstrated PK effect
Time Frame
Up to 12 months after the last study dose
Title
Safety and tolerability - adverse events
Description
Number of adverse events through study completion
Time Frame
Up to 30 days after the last study dose
Title
Safety and tolerability - death
Description
Number of deaths
Time Frame
24 months
Title
Clinical laboratory abnormalities per CTCAE
Description
Incidence of Clinical laboratory abnormalities per CTCAE
Time Frame
Up to 30 days after the last study dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participants who have had a prior resection of diagnosed HGG (2021 WHO grade 3 and 4), defined as participants who have progressed on or following standard therapy, which includes maximal surgical resection, temozolomide, and fractionated radiotherapy. Adequate archival or biopsy tissue available for testing of EGFR alterations. Participants must have measurable disease preoperatively. Have a performance status (PS) of ≤2 on the Eastern Cooperative Oncology Group (ECOG) scale. Ability to swallow oral medications. Participant has adequate bone marrow and organ function Exclusion Criteria: Pregnancy or breastfeeding. Known allergic reactions to components of the BDTX-1535. Known to have active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and active and chronic hepatitis, as determined by the investigator. Known active systemic bacterial infection, fungal infection, or detectable viral infection . Significant cardiovascular disease. Symptomatic or radiographic leptomeningeal disease. Participant has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study . Concurrent use of prohibited medications.
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 of the Ivy Brain Tumor Center
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

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.ivybraintumorcenter.org/
Description
Ivy Brain Tumor Center Website

Learn more about this trial

Study of BDTX-1535 in Recurrent High-Grade Glioma (HGG) Participants With EGFR Alterations or Fusions

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