Back to results

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

Primary Purpose

Glioblastoma

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

BI 907828

About this trial

This is an interventional treatment trial for Glioblastoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria

Inclusion criteria Part Phase 0:
- Histologically (if prior biopsy) or radiologically diagnosed glioblastoma.
- Eligible for neurosurgical tumor resection.
- 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.
- For patients, who have participated in Phase 0, the interval between the single dose of BI 907828 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.
- Inability to undergo contrast-enhanced Magnetic Resonance Imaging MRI, Glomerular Filtration Rate (GFR) <30 mL/min, or patients with metallic implants.
Exclusion criteria Part Phase 1:
- 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.
Inability to undergo contrast-enhanced Magnetic Resonance Imaging MRI, Glomerular Filtration Rate (GFR) <30 mL/min, or patients with metallic implants.

Further exclusion criteria applies.

Sites / Locations

Mayo Clinic-ArizonaRecruiting
Mayo Clinic Cancer CenterRecruiting
Mayo Clinic, RochesterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Phase 0 Part: BI 907828

Phase Ia Part: BI 907828

Arm Description

Outcomes

Primary Outcome Measures

Phase 0: Measured total concentration of BI 907828 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 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 in brain tissue homogenate from noncontrast enhancing and contrast enhancing brain tumor regions

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

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

Secondary Outcome Measures

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

Phase Ia: Progression-free survival (PFS)

Phase Ia: Maximum plasma concentration (Cmax) of BI 907828 in plasma at Cycle 1

Phase Ia: Area under the Curve of BI 907828 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz)

Phase Ia: Area under the Curve of BI 907828 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞)

Full Information

NCT ID

NCT05376800

First Posted

May 3, 2022

Last Updated

August 17, 2023

Sponsor

Boehringer Ingelheim

1. Study Identification

Unique Protocol Identification Number

NCT05376800

Brief Title

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

Official Title

A Phase 0/Ia Study of BI 907828 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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 30, 2022 (Actual)

Primary Completion Date

November 1, 2027 (Anticipated)

Study Completion Date

December 20, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Boehringer Ingelheim

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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. BI 907828 is a so-called Murine double minute 2 (MDM2) inhibitor that is being developed to treat cancer. The purpose of Part 1 of the study is to find out how BI 907828 is taken up in the tumor. Participants take a single dose of BI 907828 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 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 once every 3 weeks. Participants may continue to take BI 907828 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioblastoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Model Description

Phase 0 part: measurement of BI 907828 concentrations in brain tissue Phase Ia part: dose escalation

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

35 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Phase 0 Part: BI 907828

Arm Type

Experimental

Arm Title

Phase Ia Part: BI 907828

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

BI 907828

Other Intervention Name(s)

Brigimadlin

Intervention Description

BI 907828

Primary Outcome Measure Information:

Title

Phase 0: Measured total concentration of BI 907828 in brain tissue homogenate from noncontrast enhancing and contrast enhancing brain tumor regions

Description

Time Frame

Up to 24 hours (h)

Title

Phase 0: Calculated unbound concentration of BI 907828 in brain tissue homogenate from noncontrast enhancing and contrast enhancing brain tumor regions

Description

Time Frame

Up to 24 hours (h)

Title

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

Title

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 Measure Information:

Title

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)

Title

Phase Ia: Progression-free survival (PFS)

Time Frame

Up to 8 months.

Title

Phase Ia: Maximum plasma concentration (Cmax) of BI 907828 in plasma at Cycle 1

Time Frame

Up to Day 17

Title

Phase Ia: Area under the Curve of BI 907828 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz)

Time Frame

Up to Day 17

Title

Phase Ia: Area under the Curve of BI 907828 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞)

Time Frame

Up to Day 17

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria Inclusion criteria Part Phase 0: Histologically (if prior biopsy) or radiologically diagnosed glioblastoma. Eligible for neurosurgical tumor resection. 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. For patients, who have participated in Phase 0, the interval between the single dose of BI 907828 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. Inability to undergo contrast-enhanced Magnetic Resonance Imaging MRI, Glomerular Filtration Rate (GFR) <30 mL/min, or patients with metallic implants. Exclusion criteria Part Phase 1: 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. Inability to undergo contrast-enhanced Magnetic Resonance Imaging MRI, Glomerular Filtration Rate (GFR) <30 mL/min, or patients with metallic implants. Further exclusion criteria applies.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Boehringer Ingelheim

Phone

1-800-243-0127

clintriage.rdg@boehringer-ingelheim.com

Facility Information:

Facility Name

Mayo Clinic-Arizona

City

Phoenix

State/Province

Arizona

ZIP/Postal Code

85054

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Boehringer Ingelheim

Phone

833-602-2368

unitedstates@bitrialsupport.com

Facility Name

Mayo Clinic Cancer Center

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32224

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Boehringer Ingelheim

Phone

833-602-2368

unitedstates@bitrialsupport.com

Facility Name

Mayo Clinic, Rochester

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Boehringer Ingelheim

Phone

833-602-2368

unitedstates@bitrialsupport.com

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing 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

Links:

URL

https://www.mystudywindow.com/

Description

Related Info

Learn more about this trial

We'll reach out to this number within 24 hrs