A Study to Determine How BI 907828 (Brigimadlin) is Taken up in the Tumor (Phase 0) and to Determine the Highest Dose of BI 907828 (Brigimadlin) That Could be Tolerated (Phase 1a) in Combination With Radiation Therapy in People With a Brain Tumor Called Glioblastoma

Phase 1

Active, not recruiting

• Conditions: Glioblastoma
• Interventions: Drug: BI 907828 (Brigimadlin)

• Registration Number: NCT05376800
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

This study is open to adults with newly diagnosed glioblastoma, a type of brain tumor. The study has two parts. Part 1 is open to people who can get their brain tumor removed by surgery. Part 2 is open to people who already had such a brain surgery.

This study tests a medicine called BI 907828 (Brigimadlin). BI 907828 (Brigimadlin) is a socalled MDM2 inhibitor that is being developed to treat cancer.

The purpose of Part 1 of the study is to find out how BI 907828 (Brigimadlin) is taken up in the tumor. Participants take a single dose of BI 907828 (Brigimadlin) as a tablet before the brain surgery. Part 1 of the study takes about 1 month. During this time, participants have their brain tumor removed by surgery and visit the study site about 8 times.

The purpose of Part 2 is to find the highest dose of BI 907828 (Brigimadlin) that the participants can tolerate in combination with standard radiation therapy. During the first 6 weeks, participants get standard radiation therapy. In addition, they take a dose of BI 907828 (Brigimadlin) once every 3 weeks. Participants may continue to take BI 907828 (Brigimadlin) as long as they benefit from treatment and can tolerate it. They visit the study site regularly.

During the entire study, doctors also regularly check participants' health and take note of any unwanted effects.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-05-03
• Study First Submitted QC: 2022-05-16
• Study First Posted: 2022-05-17
• Study Start: 2022-11-07
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-17
• Last Update Posted: 2025-02-18
• Primary Completion: 2025-08-29
• Study Completion: 2025-08-29

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 0 Part: BI 907828 (Brigimadlin)	BI 907828 (Brigimadlin)	-
Phase Ia Part: BI 907828 (Brigimadlin)	BI 907828 (Brigimadlin)	-

Primary Outcome Measures

Name	Time	Method
Phase Ia: Occurrence of dose-limiting toxicity (DLT), graded according to Common Terminology Criteria for Adverse Events version 5.0, during the Maximum Tolerated Dose (MTD) evaluation period	Up to 63 Days
Phase 0: Measured total concentration of BI 907828 (Brigimadlin) in brain tissue homogenate from noncontrast enhancing and contrast enhancing brain tumor regions	Up to 24 hours (h)	Brain tissue samples will be collected after standard of care neurosurgical tumor resection.; Concentration of BI 907828 (Brigimadlin) will be quantitated in nanomole/kilogram (nmol/Kg) of tissue by validated liquid chromatography mass spectrometry (LC/MS) method.
Phase 0: Calculated unbound concentration of BI 907828 (Brigimadlin) in brain tissue homogenate from noncontrast enhancing and contrast enhancing brain tumor regions	Up to 24 hours (h)	Brain tissue samples will be collected after standard of care neurosurgical tumor resection.; Concentration of BI 907828 (Brigimadlin) will be quantitated in nanomole/kilogram (nmol/Kg) of tissue by validated liquid chromatography mass spectrometry (LC/MS) method.
Phase Ia: Occurrence of adverse events (AEs) graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 during the entire treatment period	Up to 7 months.

Secondary Outcome Measures

Name	Time	Method
Phase 0: Dose-dependent changes of expression levels of Tumor suppressor protein p53 (TP53) target genes in contrast enhancing brain regions and non-contrast enhancing brain regions	Up to 24 hours (h)
Phase Ia: Progression-free survival (PFS)	Up to 8 months.
Phase Ia: Maximum plasma concentration (Cmax) of BI 907828 (Brigimadlin) in plasma at Cycle 1	Up to Day 17
Phase Ia: Area under the Curve of BI 907828 (Brigimadlin) in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz)	Up to Day 17
Phase Ia: Area under the Curve of BI 907828 (Brigimadlin) in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞)	Up to Day 17

Trial Locations

Locations (7)

Yale New Haven Hospital; 🇺🇸 New Haven, Connecticut, United States

Mayo Clinic-Arizona; 🇺🇸 Phoenix, Arizona, United States

Mayo Clinic Cancer Center; 🇺🇸 Jacksonville, Florida, United States

Mayo Clinic, Rochester; 🇺🇸 Rochester, Minnesota, United States

UZ Leuven; 🇧🇪 Leuven, Belgium

Hospital del Mar; 🇪🇸 Barcelona, Spain

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain