Glioblastoma
Conditions
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.
Interventions
DRUGBI 907828 (Brigimadlin)
BI 907828 (Brigimadlin)
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase 0 part: measurement of BI 907828 (Brigimadlin) concentrations in brain tissue Phase Ia part: dose escalation
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Inclusion criteria Part Phase 0: * Histologically (if prior biopsy) or radiologically diagnosed glioblastoma. * Neurosurgical tumor resection is indicated and planned according to the assessment of the treating physician. * Patients must be at least 18 years old. * Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 (an ECOG of 2 is acceptable, if it is due to non-cancer-related disability, and after agreement with the sponsor). * Inclusion criteria Part Phase Ia: * Histologically demonstrated diagnosis of TP53 wild type glioblastoma harboring unmethylated O6-methylguanine-DNA-methyltransferase (MGMT) promoters. Glioblastoma definition according to 2021 World Health Organization (WHO) Classification of Central Nervous System (CNS) tumors, i.e. IDH- wild type only. * Patient has undergone neurosurgical tumor resection and is eligible for standard radiotherapy. * Patients must be neurologically stable based on the judgement of the treating physician. The use of corticosteroids and anti-seizure medication is allowed and should be at a stable or decreasing dose for at least 7 days before inclusion in the trial. Anti-seizure medication should not include agents that interact with BI 907828 (Brigimadlin). * For patients, who have participated in Phase 0, the interval between the single dose of BI 907828 (Brigimadlin) and subsequent Phase 1a treatment must be at least 21 days. Further inclusion criteria applies.
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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
| Measure | Time frame |
|---|---|
| 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: Area under the Curve of BI 907828 (Brigimadlin) in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) | Up to Day 17 |
| 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 |
Countries
Belgium, Spain, United States
Outcome results
None listed