The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05376800
Recruitment Status : Recruiting
First Posted : May 17, 2022
Last Update Posted : April 18, 2024
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.


Condition or disease Intervention/treatment Phase
Glioblastoma Drug: BI 907828 (Brigimadlin) Phase 1

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Phase 0 part: measurement of BI 907828 (Brigimadlin) concentrations in brain tissue Phase Ia part: dose escalation
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 0/Ia Study of BI 907828 (Brigimadlin) Concentrations in Brain Tissue and a Non-randomized Open-label, Dose Escalation Study of BI 907828 in Combination With Radiotherapy in Patients With Newly Diagnosed Glioblastoma
Actual Study Start Date : November 30, 2022
Estimated Primary Completion Date : November 1, 2027
Estimated Study Completion Date : December 20, 2027

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Phase 0 Part: BI 907828 (Brigimadlin) Drug: BI 907828 (Brigimadlin)
BI 907828 (Brigimadlin)
Other Name: Brigimadlin
Experimental: Phase Ia Part: BI 907828 (Brigimadlin) Drug: BI 907828 (Brigimadlin)
BI 907828 (Brigimadlin)
Other Name: Brigimadlin


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Phase 0: Measured total concentration of BI 907828 (Brigimadlin) in brain tissue homogenate from noncontrast enhancing and contrast enhancing brain tumor regions [ Time Frame: 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.


  2. Phase 0: Calculated unbound concentration of BI 907828 (Brigimadlin) in brain tissue homogenate from noncontrast enhancing and contrast enhancing brain tumor regions [ Time Frame: 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.


  3. 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 ]
  4. 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. ]

Secondary Outcome Measures :
  1. 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) ]
  2. Phase Ia: Progression-free survival (PFS) [ Time Frame: Up to 8 months. ]
  3. Phase Ia: Maximum plasma concentration (Cmax) of BI 907828 (Brigimadlin) in plasma at Cycle 1 [ Time Frame: Up to Day 17 ]
  4. 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 ]
  5. 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 ]

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05376800


Contacts
Layout table for location contacts
Contact: Boehringer Ingelheim 1-800-243-0127 clintriage.rdg@boehringer-ingelheim.com

Locations
Layout table for location information
United States, Arizona
Mayo Clinic-Arizona Recruiting
Phoenix, Arizona, United States, 85054
Contact: Boehringer Ingelheim    833-602-2368    unitedstates@bitrialsupport.com   
United States, Connecticut
Yale New Haven Hospital Recruiting
New Haven, Connecticut, United States, 06510
Contact: Boehringer Ingelheim    833-602-2368    unitedstates@bitrialsupport.com   
United States, Florida
Mayo Clinic Cancer Center Recruiting
Jacksonville, Florida, United States, 32224
Contact: Boehringer Ingelheim    833-602-2368    unitedstates@bitrialsupport.com   
United States, Minnesota
Mayo Clinic, Rochester Recruiting
Rochester, Minnesota, United States, 55905
Contact: Boehringer Ingelheim    833-602-2368    unitedstates@bitrialsupport.com   
Belgium
UZ Leuven Recruiting
Leuven, Belgium, 3000
Contact: Boehringer Ingelheim    080049616    belgique@bitrialsupport.com   
Spain
Hospital del Mar Recruiting
Barcelona, Spain, 08003
Contact: Boehringer Ingelheim    900876092    espana@bitrialsupport.com   
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain, 28041
Contact: Boehringer Ingelheim    900876092    espana@bitrialsupport.com   
Sponsors and Collaborators
Boehringer Ingelheim
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT05376800    
Other Study ID Numbers: 1403-0007
2023-506409-20-00 ( Other Identifier: CTIS )
2021-005737-17 ( EudraCT Number )
First Posted: May 17, 2022    Key Record Dates
Last Update Posted: April 18, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description:

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization).

For more details refer to:

https://www.mystudywindow.com/msw/datatransparency

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
 Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue