BDTX-1535 for Brain Tumor

Recruiting at 1 trial location

Overseen By Phase 0 Navigator

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: St. Joseph's Hospital and Medical Center, Phoenix

Must not be taking: Prohibited medications

Disqualifiers: Pregnancy, Liver disease, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: Continuous 28-day cycles

82 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial mentions that some medications are prohibited, but it doesn't specify which ones. You may need to stop certain medications, so it's best to discuss your current medications with the trial team.

What is the purpose of this trial?

This study will administer the investigational drug, BDTX-1535 to eligible patients with recurrent high-grade glioma (HGG) and newly-diagnosed glioblastoma (nGBM). 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. The study design includes a Phase 0 component with PK/PD-trigger for participant enrollment into an Expansion Phase 1 component. The primary objective of the Phase 0 component is to evaluate the PK endpoints of BDTX-1535. The primary objective of the Phase 1 component is to establish the safe dose of BDTX-1535 to be used in participants with a specified treatment regimen, three of which include standard of care radiotherapy for nGBM participants.

Research Team

Nader Sanai, MD

Principal Investigator

Chief Scientific Officer/Director of the Ivy Brain Tumor Center

Eligibility Criteria

This trial is for patients with recurrent high-grade glioma brain tumors that have progressed after standard treatments, including surgery, temozolomide chemotherapy, and radiotherapy. Participants must have specific EGFR gene changes in their tumors and be able to swallow pills. They should be relatively stable physically (ECOG PS ≤2) and not have severe cardiovascular disease, active infections or liver disease.

Inclusion Criteria

My bone marrow and organs are functioning well.

I had surgery for a high-grade glioma and have received standard treatments but my cancer has progressed.

I can perform all self-care but cannot work.

Exclusion Criteria

I have a serious heart condition.

I do not have severe infections or serious liver diseases.

I have symptoms or imaging results showing disease in the lining of my brain or spinal cord.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 0

Participants receive BDTX-1535 prior to planned resection; samples collected during surgery

1 week

1 visit (in-person, surgical)

Treatment

Participants with PK response continue with once-daily BDTX-1535 in 28-day cycles

Continuous 28-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 12 months

Treatment Details

Interventions

• BDTX-1535

Trial Overview BDTX-1535 is being tested in this study. It's a new drug aimed at blocking a growth signal in cancers linked to certain EGFR protein alterations found only in the tumors. The goal is to see if it can safely help people whose tumors depend on this signal due to these genetic changes.

Participant Groups

Group I: Arm E: Newly-Diagnosed GBM Participants with EGFR Alterations (Stupp protocol) Experimental Treatment 1 Intervention

Phase 0: Participants will receive the OBD of BDTX-1535 once daily for 5 days. The final dose will be administered 2-4 hours before tumor resection on Day 5. Participants with methylated MGMT promoter tumors demonstrating PD response will proceed to the Phase 1 Expansion component. Phase 1: Participants with methylated MGMT promoter tumors demonstrating a PD response will continue BDTX-1535 treatment at the same dose received during Phase 0, concurrently with standard of care upfront RT and temozolomide (TMZ), followed by adjuvant BDTX-1535 combined with standard of care TMZ continuously in 28-day cycles after RT. Participants will receive BDTX-1535 until disease progression, unacceptable toxicity or death, withdrawal of consent, loss to follow-up, or study termination by the sponsor.

Group II: Arm D: Newly-Diagnosed GBM Participants with EGFR Alterations (BDTX-1535 + RT Safety) Experimental Treatment 1 Intervention

Phase 0: Participants will receive the OBD of BDTX-1535 once daily for 5 days. The final dose will be administered 2-4 hours before tumor resection on Day 5. Participants with unmethylated MGMT promoter tumors demonstrating PD response will proceed to the Phase 1 Expansion component. Phase 1: Arm D: Participants with unmethylated MGMT promoter tumors demonstrating a PD response will continue BDTX-1535 treatment at the same dose received during Phase 0, concurrently with standard of care upfront RT, followed by adjuvant monotherapy with BDTX-1535 continuously in 28-day cycles after RT. Participants will receive BDTX-1535 until disease progression, unacceptable toxicity or death, withdrawal of consent, loss to follow-up, or study termination by the sponsor.

Group III: Arm C: Newly-Diagnosed GBM Participants with EGFR Alterations (OBD Determination) Experimental Treatment 1 Intervention

Phase 0: Participants in Cohort 1 will receive 200 mg of BDTX-1535 once daily for 5 days, and participants in Cohort 2 will receive 150 mg of BDTX-1535 once daily for 5 days. The final dose will be administered 2-4 hours before tumor resection on Day 5. . Participants with unmethylated MGMT promoter tumors demonstrating PK response will proceed to the Phase 1 Expansion component. The OBD will be the lowest dose that achieves the following: 9 of 12 participants show PK response and 6 of 12 participants show PD response. Phase 1: Participants with unmethylated MGMT promoter tumors demonstrating a PK response will continue BDTX-1535 treatment at the same dose received during Phase 0, concurrently with standard of care upfront RT, followed by adjuvant monotherapy with BDTX-1535 continuously in 28-day cycles after RT. Participants will receive BDTX-1535 until disease progression, unacceptable toxicity or death, withdrawal of consent, loss to follow-up, or study termination by the sponsor.

Group IV: Arm B: Recurrent High-Grade Glioma Participants with EGFR Fusion Experimental Treatment 1 Intervention

Phase 0: Participants will received BDTX-1535 once daily (Days 1-5). The dose level will be determined based on PK results from Arm A, unbound drug concentration in non-enhancing tumor. The final dose will be administered 2-4 hours before tumor resection on Day 5. Phase 1: Participants will received 200 mg BDTX-1535 treatment once daily, continuously in 28-day cycles after surgery. Participants will receive BDTX-1535 until disease progression, unacceptable toxicity or death, withdrawal of consent, loss to follow-up, or study termination by the sponsor.

Group V: Arm A: Recurrent High-Grade Glioma Participants with EGFR Alterations Experimental Treatment 1 Intervention

Phase 0: Cohort 1 will receive 200 mg BDTX-1535 once daily (Days 1-5). Cohort 2 will receive 400 mg BDTX-1535 three times over one week (Days 1, 3, and 5). The final dose will be administered 2-4 hours before tumor resection on Day 5. Phase 1: Participants will received 200 mg BDTX-1535 treatment once daily, continuously in 28-day cycles after surgery. Participants will receive BDTX-1535 until disease progression, unacceptable toxicity or death, withdrawal of consent, loss to follow-up, or study termination by the sponsor.

Who Is Running the Clinical Trial?

St. Joseph's Hospital and Medical Center, Phoenix

Lead Sponsor

Trials

69

Recruited

17,400+

Ivy Brain Tumor Center

Collaborator

Trials

12

Recruited

910+

Barrow Neurological Institute

Collaborator

Trials

27

Recruited

7,100+