Brigimadlin + Radiation for Glioblastoma

Recruiting at 6 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Boehringer Ingelheim

Must not be taking: Restricted medications

Disqualifiers: TP53 mutant, IDH mutant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 8

24 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot take any drugs that might interfere with the trial. You can continue using corticosteroids and anti-seizure medications if they are stable or decreasing in dose, but anti-seizure medications must not interact with the trial drug, Brigimadlin.

What data supports the effectiveness of the treatment Brigimadlin + Radiation for Glioblastoma?

Research shows that using radioactive seeds like iridium-192 and iodine-125 in brain tumors can help target the tumor more precisely, potentially improving outcomes without causing serious complications. Additionally, intensity-modulated radiotherapy (IMRT) has been effective in treating high-grade gliomas by delivering higher doses of radiation directly to the tumor while sparing healthy tissue. ^{1 2 3 4 5}

Is the combination of Brigimadlin and radiation therapy safe for humans?

Various forms of radiation therapy, including those using radioactive seeds like GammaTile and I-125, have been studied for brain tumors and are generally considered safe with minimal serious complications reported. These therapies have been used for many years and are FDA-approved for certain brain tumors, indicating a recognized safety profile. ^{1 6 7 8 9}

What makes the Brigimadlin + Radiation treatment for glioblastoma unique?

The Brigimadlin + Radiation treatment for glioblastoma is unique because it combines a novel drug, Brigimadlin, with advanced radiation techniques like intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT), which aim to precisely target the tumor while minimizing damage to surrounding healthy tissue. This approach may offer a more targeted and potentially effective treatment option compared to traditional methods. ^{1 6 10 11 12}

Eligibility Criteria

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.

Inclusion Criteria

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

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

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

Exclusion Criteria

My grade IV astrocytoma is IDH mutant.

I have had treatment for glioblastoma, but not in a Phase 0 trial.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 0

Participants take a single dose of BI 907828 (Brigimadlin) as a tablet before brain surgery to assess drug uptake in the tumor

4 weeks

8 visits (in-person)

Phase 1a

Participants receive BI 907828 (Brigimadlin) in combination with standard radiation therapy to determine the highest tolerable dose

6 weeks

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• BI 907828
• Radiation Therapy

Trial Overview 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.

Participant Groups

Group I: Phase Ia Part: BI 907828 (Brigimadlin) Experimental Treatment 1 Intervention

Group II: Phase 0 Part: BI 907828 (Brigimadlin) Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Findings from Research

A new method for delivering interstitial radiation therapy using 192Ir seeds in brain tumors has been developed, which involves CT-guided stereotactic localization and computerized dose planning.

Preliminary results from seven patients show promising outcomes with no serious complications reported, indicating the method's potential safety and efficacy in treating brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of brain tumors with iridium-192 seeds. Kaneko, I., Noguchi, M., Kogure, T., et al.[2019]

In a study of 58 patients with spinal metastases treated with intensity modulated radiation therapy using a simultaneous integrated boost (SSIB), 82% of those who reported pain before treatment experienced significant pain relief after therapy, indicating high efficacy in pain management.

The treatment demonstrated a local control rate of 88% at one year and 74% at two years, with limited acute toxicities, suggesting that SSIB is a safe and effective option for patients with spine metastases who cannot undergo stereotactic radiosurgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Dose-Escalated Radiation Therapy With a Simultaneous Integrated Boost for the Treatment of Spinal Metastases. Florez, MA., De, B., Cavazos, A., et al.[2023]

GammaTile® Surgically Targeted Radiation Therapy (STaRT) offers a novel approach to brain tumor treatment by using a bioresorbable tile that delivers radiation while minimizing direct contact with brain tissue, which helps reduce normal brain toxicity.

This therapy has been FDA approved since 2018 for recurrent brain tumors and expanded in 2020 to include newly-diagnosed malignant tumors, with ongoing trials aimed at comparing its efficacy and safety against standard radiation treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgically targeted radiation therapy (STaRT) trials for brain neoplasms: A comprehensive review. Odia, Y., Gutierrez, AN., Kotecha, R.[2023]

GammaTile intracranial brachytherapy, using cesium-131 seeds, was successfully performed during an awake craniotomy in a 50-year-old patient with a glioblastoma, demonstrating the safety and feasibility of this approach.

The procedure allowed for precise tumor resection and custom implantation of the GammaTiles, ensuring effective treatment while preserving critical brain functions, such as speech, due to real-time language mapping.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of GammaTile intracranial brachytherapy implanted during awake craniotomy. McClelland, S., Gardner, UG., Le, Y., et al.[2021]

Intraoperative radiotherapy (IORT) for Glioblastoma results in lower exposure to organs-at-risk (OARs) compared to pre-operative single-fraction stereotactic radiosurgery (SRS), making it a safer option for patients.

The study analyzed 17 treatment plans and found that while SRS provided excellent target coverage, IORT led to significantly lower doses to critical structures like the optic nerves and retina, suggesting it may be a more effective approach in minimizing side effects during dose escalation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric Comparison of Upfront Boosting With Stereotactic Radiosurgery Versus Intraoperative Radiotherapy for Glioblastoma. Sarria, GR., Smalec, Z., Muedder, T., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Treatment of brain tumors with iridium-192 seeds. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Computer applications to radioactive-seed: brain-tumor implants. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Simultaneous integrated boost intensity-modulated radiotherapy in patients with high-grade gliomas. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Dose-Escalated Radiation Therapy With a Simultaneous Integrated Boost for the Treatment of Spinal Metastases. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Stereotactic interstitial brachytherapy for the treatment of oligodendroglial brain tumors. [2018]

6. Germany pubmed.ncbi.nlm.nih.gov

Outcome of Adult Brain Tumor Consortium (ABTC) prospective dose-finding trials of I-125 balloon brachytherapy in high-grade gliomas: challenges in clinical trial design and technology development when MRI treatment effect and recurrence appear similar. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Surgically targeted radiation therapy (STaRT) trials for brain neoplasms: A comprehensive review. [2023]

8. China pubmed.ncbi.nlm.nih.gov

[Expert consensus on the treatment of glioma with radioactive seeds]. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Safety and efficacy of GammaTile intracranial brachytherapy implanted during awake craniotomy. [2021]

10. China pubmed.ncbi.nlm.nih.gov

Efficacy of scalp-sparing volumetric-modulated arc therapy approach in reducing scalp radiation dose for patients with glioblastoma: a cross-sectional study. [2023]

11. France pubmed.ncbi.nlm.nih.gov

[Radiotherapy in adult glioblastomas]. [2016]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Dosimetric Comparison of Upfront Boosting With Stereotactic Radiosurgery Versus Intraoperative Radiotherapy for Glioblastoma. [2022]