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

High Grade Glioma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06072586
• Other study ID #: 2023-20
• Secondary ID: 24-500-090-34-38
• Status: Recruiting
• Phase: Early Phase 1
• Start date: October 18, 2023
• Est. completion date: October 31, 2025

Study information

• Verified date: November 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 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 22
• Est. completion date: October 31, 2025
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Glioma
• High Grade Glioma

Intervention

Drug:
• BDTX-1535
BDTX-1535 is an inhibitor of EGFR mutations

Locations

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

Sponsors (3)

Lead Sponsor	Collaborator
St. Joseph's Hospital and Medical Center, Phoenix	Barrow Neurological Institute, Ivy Brain Tumor Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Unbound concentration of BDTX-1535 in tumor tissue	Unbound BDTX-1535 concentration in Gd-enhancing and Gd-non-enhancing tumor tissue	Phase 0 Intraoperative Sample
Primary	Total concentration of BDTX-1535 in tumor tissue	Total BDTX-1535 concentration in Gd-enhancing and Gd-non-enhancing tumor tissue	Phase 0 Intraoperative Sample
Primary	Progression Free Survival (PFS)	Rate of 6-month progression-free survival	6 months
Secondary	Concentration of BDTX-1535 in CSF	BDTX-1535 level in CSF will be determined	Phase 0 Intraoperative sample
Secondary	Percentage of pEGFR positive cells in tumor tissue	Expression of pEGFR in BDTX-1535 treated HGG tissue compared to archival tissue.	Phase 0 Intraoperative Sample
Secondary	Percentage of pERK positive cells in tumor tissue	Expression of pERK in BDTX-1535 treated HGG tissue compared to archival tissue.	Phase 0 Intraoperative Sample
Secondary	Overall survival (OS)	Median overall survival in participants with demonstrated PK effect	Up to 12 months after the last study dose
Secondary	Safety and tolerability - adverse events	Number of adverse events through study completion	Up to 30 days after the last study dose
Secondary	Safety and tolerability - death	Number of deaths	24 months
Secondary	Clinical laboratory abnormalities per CTCAE	Incidence of Clinical laboratory abnormalities per CTCAE	Up to 30 days after the last study dose

External Links

•   Ivy Brain Tumor Center Website