Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05376800
Other study ID # 1403-0007
Secondary ID 2023-506409-20-0
Status Recruiting
Phase Phase 1
First received
Last updated
Start date November 30, 2022
Est. completion date December 20, 2027

Study information

Verified date April 2024
Source Boehringer Ingelheim
Contact Boehringer Ingelheim
Phone 1-800-243-0127
Email clintriage.rdg@boehringer-ingelheim.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Recruiting
Enrollment 35
Est. completion date December 20, 2027
Est. primary completion date November 1, 2027
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 - Exclusion criteria Part Phase 0: - Known TP53 mutant glioblastoma (Note: testing is not mandatory for inclusion). - Known Isocitrate dehydrogenase (IDH) mutant grade IV astrocytoma (Note: testing is not mandatory for inclusion). - Patient who must receive or intends to receive restricted medications. - Patients with pacemakers or other metallic implants that can interfere with the magnetic field during Magnetic Resonance Imaging (MRI) investigations. - Inability to undergo contrast-enhanced MRI (Glomerular Filtration Rate (GFR) <30 mL/min). - Exclusion criteria Part Phase Ia: - Patients who have received previous systemic therapy (with the exception of patients who participated in Phase 0) or radiotherapy for glioblastoma. - Patients who must or intend to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial. - Patients with pacemakers or other metallic implants that can interfere with the magnetic field during MRI investigations. - Inability to undergo contrast-enhanced MRI (GFR <30 mL/min). Further exclusion criteria applies.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
BI 907828 (Brigimadlin)
BI 907828 (Brigimadlin)

Locations

Country Name City State
Belgium UZ Leuven Leuven
Spain Hospital del Mar Barcelona
Spain Hospital Universitario 12 de Octubre Madrid
United States Mayo Clinic Cancer Center Jacksonville Florida
United States Yale New Haven Hospital New Haven Connecticut
United States Mayo Clinic-Arizona Phoenix Arizona
United States Mayo Clinic, Rochester Rochester Minnesota

Sponsors (1)

Lead Sponsor Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Belgium,  Spain, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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.
Up to 24 hours (h)
Primary 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.
Up to 24 hours (h)
Primary 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
Primary 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 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)
Secondary Phase Ia: Progression-free survival (PFS) Up to 8 months.
Secondary Phase Ia: Maximum plasma concentration (Cmax) of BI 907828 (Brigimadlin) in plasma at Cycle 1 Up to Day 17
Secondary 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
Secondary Phase Ia: Area under the Curve of BI 907828 (Brigimadlin) in plasma over the time interval from 0 extrapolated to infinity (AUC0-8) Up to Day 17
See also
  Status Clinical Trial Phase
Recruiting NCT05664243 - A Phase 1b / 2 Drug Resistant Immunotherapy With Activated, Gene Modified Allogeneic or Autologous γδ T Cells (DeltEx) in Combination With Maintenance Temozolomide in Subjects With Recurrent or Newly Diagnosed Glioblastoma Phase 1/Phase 2
Completed NCT02768389 - Feasibility Trial of the Modified Atkins Diet and Bevacizumab for Recurrent Glioblastoma Early Phase 1
Recruiting NCT05635734 - Azeliragon and Chemoradiotherapy in Newly Diagnosed Glioblastoma Phase 1/Phase 2
Completed NCT03679754 - Evaluation of Ad-RTS-hIL-12 + Veledimex in Subjects With Recurrent or Progressive Glioblastoma, a Substudy to ATI001-102 Phase 1
Completed NCT01250470 - Vaccine Therapy and Sargramostim in Treating Patients With Malignant Glioma Phase 1
Terminated NCT03927222 - Immunotherapy Targeted Against Cytomegalovirus in Patients With Newly-Diagnosed WHO Grade IV Unmethylated Glioma Phase 2
Recruiting NCT03897491 - PD L 506 for Stereotactic Interstitial Photodynamic Therapy of Newly Diagnosed Supratentorial IDH Wild-type Glioblastoma Phase 2
Active, not recruiting NCT03587038 - OKN-007 in Combination With Adjuvant Temozolomide Chemoradiotherapy for Newly Diagnosed Glioblastoma Phase 1
Completed NCT01922076 - Adavosertib and Local Radiation Therapy in Treating Children With Newly Diagnosed Diffuse Intrinsic Pontine Gliomas Phase 1
Recruiting NCT04391062 - Dose Finding for Intraoperative Photodynamic Therapy of Glioblastoma Phase 2
Active, not recruiting NCT03661723 - Pembrolizumab and Reirradiation in Bevacizumab Naïve and Bevacizumab Resistant Recurrent Glioblastoma Phase 2
Active, not recruiting NCT02655601 - Trial of Newly Diagnosed High Grade Glioma Treated With Concurrent Radiation Therapy, Temozolomide and BMX-001 Phase 2
Completed NCT02206230 - Trial of Hypofractionated Radiation Therapy for Glioblastoma Phase 2
Completed NCT03493932 - Cytokine Microdialysis for Real-Time Immune Monitoring in Glioblastoma Patients Undergoing Checkpoint Blockade Phase 1
Terminated NCT02709889 - Rovalpituzumab Tesirine in Delta-Like Protein 3-Expressing Advanced Solid Tumors Phase 1/Phase 2
Recruiting NCT06058988 - Trastuzumab Deruxtecan (T-DXd) for People With Brain Cancer Phase 2
Completed NCT03018288 - Radiation Therapy Plus Temozolomide and Pembrolizumab With and Without HSPPC-96 in Newly Diagnosed Glioblastoma (GBM) Phase 2
Not yet recruiting NCT04552977 - A Trail of Fluzoparil in Combination With Temozolomide in Patients With Recurrent Glioblastoma Phase 2
Withdrawn NCT03980249 - Anti-Cancer Effects of Carvedilol With Standard Treatment in Glioblastoma and Response of Peripheral Glioma Circulating Tumor Cells Early Phase 1
Withdrawn NCT02876003 - Efficacy and Safety of G-202 in PSMA-Positive Glioblastoma Phase 2

External Links