What is the mechanism of action of this treatment?

Liposarcoma treatments often target specific cellular mechanisms to inhibit tumor growth. Brigimadlin (BI 907828) is an MDM2 inhibitor that works by blocking the MDM2 protein, which normally inhibits the tumor suppressor p53. By inhibiting MDM2, p53 activity is restored, leading to increased cancer cell death. Doxorubicin, a widely used chemotherapy agent, intercalates DNA and inhibits topoisomerase II, preventing DNA replication and leading to cell death. Eribulin inhibits microtubule dynamics, disrupting mitotic spindle formation and causing cell cycle arrest. Gemcitabine, often combined with other agents like docetaxel, is a nucleoside analog that incorporates into DNA, causing chain termination and apoptosis. These mechanisms are crucial for liposarcoma patients as they target the cancer cells' ability to proliferate and survive, offering potential therapeutic benefits.

What side effects are associated with this type of intervention?

Common treatments for liposarcoma, such as doxorubicin, are associated with side effects including nausea, vomiting, fatigue, and neutropenia. MDM2 inhibitors like Brigimadlin (BI 907828) are being studied for their potential in treating liposarcoma, and while specific side effects for Brigimadlin are not detailed, MDM2 inhibitors generally may cause side effects such as gastrointestinal disturbances, hematologic toxicities, and fatigue. Patients should discuss these potential side effects with their healthcare provider to make an informed decision.

What prior FDA approvals exist?

The FDA has approved several treatments for liposarcoma, with doxorubicin being a commonly used chemotherapy agent. Doxorubicin is often used alone or in combination with other drugs for treating advanced soft tissue sarcomas, including liposarcoma. While the context does not provide specific information on FDA-approved MDM2 inhibitors for liposarcoma, brigimadlin (BI 907828) is currently being studied as a potential treatment. Other treatments for advanced liposarcoma include pazopanib, a tyrosine kinase inhibitor, which has shown efficacy in patients who have progressed on prior chemotherapy.

What other types of research exist?

Promising novel alternatives to Brigimadlin (BI 907828) for liposarcoma patients include: 1) Indisulam, a sulfonamide that inhibits cell cycle progression, currently in phase II trials for solid tumors. 2) Batimastat, a matrix metalloproteinase inhibitor, which has shown efficacy in reducing tumor regrowth and metastasis in preclinical models. 3) Everolimus, an mTOR inhibitor, which has been studied in combination with other agents for enhanced efficacy in cancer treatment.

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MDM2 Inhibitor

BI 907828 vs Doxorubicin for Liposarcoma

Phase 2 & 3

Waitlist Available

Research Sponsored by Boehringer Ingelheim

Eligibility Criteria Checklist

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

Must have

Written pathology report indicating the diagnosis of DDLPS with positive mouse double minute 2 homolog (MDM2) immunohistochemistry or MDM2 amplification as demonstrated by fluorescence in situ hybridization or next generation sequencing (NGS) must be available

Formalin fixed paraffin embedded tumor blocks or slides must be available for retrospective histopathological central review

Must not have

Known mutation in the TP53 gene (screening for TP53 status is not required)

Major surgery (major according to the investigator's assessment) performed within 4 weeks prior to randomization or planned within 6 months after screening

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 50 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is for adults with advanced dedifferentiated liposarcoma who are not receiving other treatments. It compares a new drug, brigimadlin (BI 907828), which blocks a protein that helps cancer grow, with doxorubicin, an existing drug that damages cancer cell DNA. Participants receive either brigimadlin as tablets or doxorubicin through a vein. Doctors monitor tumor size and health regularly. The new drug aims to be effective and less toxic compared to conventional treatments.

Who is the study for?

Adults with a specific cancer called dedifferentiated liposarcoma, who haven't had systemic therapy for it, can join this trial. They must have measurable tumor growth and be in good health otherwise. Women of childbearing age and men must use effective birth control.

What is being tested?

The trial compares BI 907828, an MDM2 inhibitor pill taken every three weeks, against doxorubicin, a standard cancer infusion treatment. Participants may switch to BI 907828 if doxorubicin isn't helping them.

What are the potential side effects?

Possible side effects include typical reactions to cancer medications such as nausea, fatigue, hair loss (with doxorubicin), and potential blood cell count changes. Specific side effects of BI 907828 are not detailed but could resemble other chemotherapy drugs.

Eligibility Criteria

Inclusion Criteria

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

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My pathology report shows a DDLPS diagnosis with positive MDM2.

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My cancer samples are stored and available for review.

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I am fully active or restricted in physically strenuous activity but can do light work.

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My cancer is a type of advanced liposarcoma that cannot be removed by surgery.

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I am willing to have a tumor biopsy as required.

Exclusion Criteria

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

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I have a known TP53 gene mutation.

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I haven't had major surgery in the last 4 weeks and don't plan any in the next 6 months.

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

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 50 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 50 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 50 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

Progression-free survival

Secondary study objectives

Change from baseline in EQ-5D5L (European Quality of Life 5 dimensions 5 level)

Change from baseline in QLQ-C30 (Quality of Life questionnaire C30)

Change from baseline in fatigue

+5 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

4Treatment groups

Experimental Treatment

Active Control

Group I: Brigimadlin (BI 907828) low doseExperimental Treatment1 Intervention

Phase II

Group II: Brigimadlin (BI 907828) high doseExperimental Treatment1 Intervention

Phase II

Group III: Brigimadlin (BI 907828) armExperimental Treatment1 Intervention

Phase III

Group IV: Doxorubicin armActive Control1 Intervention

Phase II/III

0 / 8Eligibility 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

Liposarcoma treatments often target specific cellular mechanisms to inhibit tumor growth. Brigimadlin (BI 907828) is an MDM2 inhibitor that works by blocking the MDM2 protein, which normally inhibits the tumor suppressor p53. By inhibiting MDM2, p53 activity is restored, leading to increased cancer cell death. Doxorubicin, a widely used chemotherapy agent, intercalates DNA and inhibits topoisomerase II, preventing DNA replication and leading to cell death. Eribulin inhibits microtubule dynamics, disrupting mitotic spindle formation and causing cell cycle arrest. Gemcitabine, often combined with other agents like docetaxel, is a nucleoside analog that incorporates into DNA, causing chain termination and apoptosis. These mechanisms are crucial for liposarcoma patients as they target the cancer cells' ability to proliferate and survive, offering potential therapeutic benefits.

Effect of matrix metalloproteinase inhibitor batimastat on breast cancer regrowth and metastasis in athymic mice.Therapeutic effects of the novel Leucyl-tRNA synthetase inhibitor BC-LI-0186 in non-small cell lung cancer.Sporadic Angiomyolipomas Growth Kinetics While on Everolimus: Results of a Phase II Trial.