What side effects are associated with this type of intervention?

Common treatments for glioblastoma include surgery, radiation therapy, and chemotherapy. Side effects of these treatments can vary but often include fatigue, headaches, nausea, vomiting, and hair loss. Specifically, for MDM2 inhibitors like BI 907828, side effects may include gastrointestinal issues, hematologic toxicity, and potential impacts on liver function. Radiation therapy can also cause skin irritation, brain swelling, and cognitive changes. It is important for patients to discuss these potential side effects with their healthcare provider to manage them effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for Glioblastoma, including temozolomide, an oral alkylating agent, and bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF). These treatments aim to inhibit tumor growth and angiogenesis. While specific FDA approvals for MDM2 inhibitors in Glioblastoma are not mentioned, ongoing research, such as the trial involving BI 907828, indicates a growing interest in targeting the MDM2 pathway to treat this aggressive brain tumor.

What other types of research exist?

Promising novel alternatives to BI 907828 for glioblastoma patients include: 1) Bevacizumab, an anti-VEGF antibody, which has shown efficacy in reducing tumor growth and improving symptoms. 2) Everolimus, an mTORC1 inhibitor, which has demonstrated potential in slowing tumor progression. 3) Dabrafenib plus trametinib, targeting BRAF V600E mutations, which has shown sustained tumor control in gliomas with this mutation. 4) Pembrolizumab, an immune checkpoint inhibitor, which has shown promise in enhancing the immune response against glioblastoma.

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MDM2 Inhibitor

Brigimadlin + Radiation for Glioblastoma

Q: What is the mechanism of action of this treatment?

Glioblastoma treatments often target the rapid and uncontrolled cell growth characteristic of this aggressive brain tumor. MDM2 inhibitors like BI 907828 work by blocking the MDM2 protein, which normally inhibits the tumor suppressor p53. By inhibiting MDM2, p53 activity is restored, leading to increased tumor cell death. Radiation therapy damages the DNA of cancer cells, preventing them from dividing and causing them to die. Chemotherapy agents, such as temozolomide, work by alkylating/methylating DNA, which also leads to cell death. These treatments are crucial for Glioblastoma patients as they aim to control tumor growth, improve survival rates, and alleviate symptoms.

Phase 1

Recruiting

Research Sponsored by Boehringer Ingelheim

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histologically (if prior biopsy) or radiologically diagnosed glioblastoma

Eligible for neurosurgical tumor resection

Must not have

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 8 months.

Awards & highlights

No Placebo-Only Group

Summary

This trial tests BI 907828, a new drug for treating brain tumors. It targets adults with newly diagnosed glioblastoma. The drug works by blocking a protein that helps cancer cells grow. The study aims to see how well the drug is absorbed in the tumor and find the highest safe dose when combined with radiation therapy.

Who is the study for?

Adults with newly diagnosed glioblastoma, a type of brain tumor. Part 1 is for those awaiting surgery; Part 2 for post-surgery patients eligible for radiation therapy. Must be over 18, have good performance status (0 or 1), and stable health on certain medications. Excludes those with specific genetic mutations, prior systemic therapy/radiotherapy (except Phase 0 participants), poor kidney function, or incompatible implants.

What is being tested?

The study tests BI 907828 (Brigimadlin), an MDM2 inhibitor cancer drug. Part 1 assesses how the drug accumulates in the tumor after one dose before surgery. In Part 2, the highest tolerable dose is sought alongside standard radiation therapy over six weeks with regular visits and potential continuation if beneficial.

What are the potential side effects?

While not explicitly listed in the provided information, side effects may include typical reactions to cancer drugs such as nausea, fatigue, blood count changes and increased risk of infections due to immune system suppression.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My diagnosis of glioblastoma was confirmed through a biopsy or imaging tests.

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I am a candidate for surgery to remove a brain tumor.

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I am 18 years old or older.

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My glioblastoma is TP53 wild type and has unmethylated MGMT promoters.

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I have had surgery to remove a brain tumor and can undergo standard radiotherapy.

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I have been diagnosed with glioblastoma through a biopsy or imaging tests.

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I am a candidate for surgery to remove a brain tumor.

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I am 18 years old or older.

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My glioblastoma is TP53 wild type and has unmethylated MGMT promoters.

Select...

I had surgery to remove a brain tumor and can have standard radiotherapy.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I must take or plan to take certain restricted medications.

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I cannot have an MRI due to kidney issues or metal implants.

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I am not taking any medication that could interfere with the trial.

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I cannot have an MRI due to kidney issues or metal implants.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 8 months.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 8 months.

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 8 months. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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

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

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

+1 more

Secondary study objectives

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

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)

+2 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Phase Ia Part: BI 907828 (Brigimadlin)Experimental Treatment1 Intervention

Group II: Phase 0 Part: BI 907828 (Brigimadlin)Experimental Treatment1 Intervention

0 / 14Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Glioblastoma treatments often target the rapid and uncontrolled cell growth characteristic of this aggressive brain tumor. MDM2 inhibitors like BI 907828 work by blocking the MDM2 protein, which normally inhibits the tumor suppressor p53. By inhibiting MDM2, p53 activity is restored, leading to increased tumor cell death. Radiation therapy damages the DNA of cancer cells, preventing them from dividing and causing them to die. Chemotherapy agents, such as temozolomide, work by alkylating/methylating DNA, which also leads to cell death. These treatments are crucial for Glioblastoma patients as they aim to control tumor growth, improve survival rates, and alleviate symptoms.