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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
BI 907828 (Brigimadlin)
Mayo Clinic-Arizona
Phoenix, Arizona, United States
Yale New Haven Hospital
New Haven, Connecticut, 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
Phase 0: Measured total concentration of BI 907828 (Brigimadlin) in brain tissue homogenate from noncontrast enhancing and contrast enhancing brain tumor regions
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.
Time frame: Up to 24 hours (h)
Phase 0: Calculated unbound concentration of BI 907828 (Brigimadlin) in brain tissue homogenate from noncontrast enhancing and contrast enhancing brain tumor regions
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.
Time frame: Up to 24 hours (h)
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
Time frame: Up to 63 Days
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
Time frame: Up to 7 months.
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
Time frame: Up to 24 hours (h)
Phase Ia: Progression-free survival (PFS)
Time frame: Up to 8 months.
Phase Ia: Maximum plasma concentration (Cmax) of BI 907828 (Brigimadlin) in plasma at Cycle 1
Time frame: 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)
Time frame: 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-∞)
Time frame: Up to Day 17
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