BI 907828 vs Doxorubicin for Liposarcoma

Not currently recruiting at 373 trial locations

Overseen By Additional US locations available on demand. Please contact for options.

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Boehringer Ingelheim

Must not be taking: Anthracyclines

Disqualifiers: TP53 mutation, Other malignancies, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: Up to 30 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cancer drug, brigimadlin (BI 907828), against an existing one, doxorubicin, for treating dedifferentiated liposarcoma. The researchers aim to compare the effectiveness of brigimadlin with doxorubicin, which is already used for this cancer. Participants will receive either brigimadlin in tablet form or doxorubicin through an IV every three weeks. The study seeks individuals with advanced liposarcoma who are not currently receiving other cancer treatments and have a measurable tumor. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it mentions that patients who need to continue taking certain restricted medications or drugs that might interfere with the trial are excluded. It's best to discuss your current medications with the trial team to see if they are allowed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that brigimadlin (BI 907828), the new treatment being tested, is generally safe. Most participants in earlier studies used it without serious issues. Research suggests it may help treat certain cancers. Participants mostly experienced mild to moderate side effects, which were usually manageable with standard care.

Doxorubicin, the other treatment in the trial, is a well-known cancer drug already used for liposarcoma. Its side effects, such as nausea or low blood cell counts, are well-documented.

Both treatments have undergone previous testing, providing some confidence in their safety for participants. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for liposarcoma?

Researchers are excited about brigimadlin because it offers a potentially new way to tackle advanced or metastatic dedifferentiated liposarcoma (DDLPS). Unlike the standard treatment, doxorubicin, which is a chemotherapy drug administered intravenously, brigimadlin is taken orally, which could be more convenient for patients. Brigimadlin is also notable for its mechanism of action, as it targets the MDM2-p53 interaction, which is crucial in controlling cell growth and death. This approach could lead to more effective management of DDLPS, offering hope for better outcomes compared to traditional therapies.

What evidence suggests that this trial's treatments could be effective for liposarcoma?

Research has shown that brigimadlin (BI 907828), one of the treatments studied in this trial, may help treat liposarcoma, a type of cancer. In earlier studies, 11.1% of patients experienced tumor shrinkage, and 74.1% had stable disease without worsening. Brigimadlin blocks a protein called MDM2, which aids cancer growth. This method has shown particular effectiveness in lab tests for liposarcoma. Meanwhile, doxorubicin, the other treatment option in this trial, is a well-known cancer drug already used for treating liposarcoma and other cancers. This trial compares these two treatments to determine which is more effective for this cancer. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

I have a tumor that can be measured by scans.

My organs are working well.

My pathology report shows a DDLPS diagnosis with positive MDM2.

Exclusion Criteria

I have received treatment for liposarcoma before.

I have had cancer other than DDLPS or WDLPS in the last 5 years, but it was treated and considered cured.

I have been treated with anthracyclines before, but any other cancer treatment was over 5 years ago, except hormone therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either brigimadlin (BI 907828) or doxorubicin every 3 weeks. Participants can switch to brigimadlin if they do not benefit from doxorubicin.

Up to 30 months

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including regular checks on tumor size and health assessments.

Up to 50 months

What Are the Treatments Tested in This Trial?

Interventions

• BI 907828
• Doxorubicin

Trial Overview 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.

How Is the Trial Designed?

Group I: Brigimadlin 45 mg q3w Experimental Treatment 1 Intervention

Patients with advanced or metastatic dedifferentiated liposarcoma (DDLPS) received 45 milligram (mg) brigimadlin taken orally on day 1 of each 21-day cycle (q3w).

Group II: Brigimadlin 30 mg q3w Experimental Treatment 1 Intervention

Patients with advanced or metastatic dedifferentiated liposarcoma (DDLPS) received 30 milligram (mg) brigimadlin taken orally on day 1 of each 21-day cycle (q3w).

Group III: Doxorubicin Active Control 1 Intervention

Patients with advanced or metastatic dedifferentiated liposarcoma (DDLPS) received one intravenous infusion of 75 milligram per square meter (mg/m2) on Day 1 of each 21-day cycle (q3w) until a maximum cumulative dose of 450 mg/m2 (approximately 6 cycles).

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Published Research Related to This Trial

In a study comparing 40 patients treated with Lipodox® to 120 matched patients treated with Doxil®, Lipodox® showed a significantly lower overall response rate of 4.3% compared to 18% for Doxil®, indicating reduced efficacy in treating recurrent ovarian cancer.

Despite similar toxicity profiles between Lipodox® and Doxil®, the lack of equivalent efficacy suggests that further prospective clinical studies are needed before Lipodox® can be considered a suitable substitute for Doxil®.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is it equivalent? Evaluation of the clinical activity of single agent Lipodox® compared to single agent Doxil® in ovarian cancer treatment. Smith, JA., Costales, AB., Jaffari, M., et al.[2019]

Probucol pretreatment significantly increased the clearance of doxorubicin (DOX) in plasma and altered its distribution in various tissues, suggesting it affects the pharmacokinetics of DOX.

Probucol also provided cardioprotection against DOX-induced toxicity by improving the ATP/ADP ratio and reducing markers of heart damage, indicating its potential as a protective agent during chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New aspects in probucol cardioprotection against doxorubicin-induced cardiotoxicity. El-Demerdash, E., Ali, AA., Sayed-Ahmed, MM., et al.[2013]

The combination of Doxil (40 mg/m2) and vinorelbine (30 mg/m2) was found to be effective in treating metastatic breast cancer in a phase I study involving 30 women, with a recommended schedule for further testing.

This combination therapy demonstrated a favorable toxicity profile, with minimal severe side effects like neutropenia and a low incidence of significant nausea, vomiting, or hair loss, making it a promising option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of Doxil and vinorelbine in metastatic breast cancer. Burstein, HJ., Ramirez, MJ., Petros, WP., et al.[2020]

Liposomal formulations of doxorubicin, such as Doxil and Myocet, reduce the risk of heart-related toxicities associated with the free form of doxorubicin by sequestering the drug away from the heart and targeting it more towards tumors and other organs like the liver and spleen.

While liposomal doxorubicin allows for a greater cumulative dose to be safely administered, it comes with its own toxicities, such as palmar-plantar erythrodysaesthesia with Doxil, highlighting the need for careful consideration in treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of liposomal formulations of doxorubicin with drug administered in free form: changing toxicity profiles. Waterhouse, DN., Tardi, PG., Mayer, LD., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10401071/

The MDM2–p53 Antagonist Brigimadlin (BI 907828) in ... Preliminary efficacy was encouraging (11.1% overall response and 74.1% disease control rates), particularly in patients with well-differentiated or ...

2. esmoopen.com esmoopen.com/article/S2059-7029(24)00214-X/fulltext

56O A phase Ia/Ib study of the MDM2-p53 antagonist ... 56O A phase Ia/Ib study of the MDM2-p53 antagonist brigimadlin (BI 907828): Safety and efficacy in patients with dedifferentiated liposarcoma · Download PDF ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05218499

Brightline-1: A Study to Compare Brigimadlin (BI 907828 ... The purpose of this study is to compare a medicine called brigimadlin (BI 907828) with doxorubicin in people with liposarcoma. Brigimadlin (BI 907828) is a ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.11554

A phase Ia/Ib, dose-escalation/expansion study of the ... BI 907828 is a highly potent MDM2–p53 antagonist which has demonstrated preclinical antitumor activity, particularly in TP53-wt MDM2-amplified DDLPS models.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06058793

NCT06058793 | Brightline-4: A Study to Test How Well ... The purpose of this study is to find out whether a medicine called brigimadlin (BI 907828) is tolerated by and helps people with DDLPS. Brigimadlin is a so- ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37269344/

The MDM2-p53 Antagonist Brigimadlin (BI 907828) in Patients ... We report phase Ia data indicating that the oral MDM2-p53 antagonist brigimadlin has a manageable safety profile and shows encouraging signs ...

7. onclive.com onclive.com/view/bi-907828-demonstrates-early-efficacy-safety-in-mdm2-amplified-dedifferentiated-liposarcoma

BI 907828 Demonstrates Early Efficacy, Safety in MDM2- ... The oral MDM2/p53 antagonist BI 907828 elicited preliminary antitumor activity and had a manageable safety profile in patients with MDM2-amplified ...