BI 907828 vs Doxorubicin for Liposarcoma

Recruiting at 360 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

401 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug Doxorubicin for treating liposarcoma?

Doxorubicin, a widely used cancer drug, has been shown to be effective in treating various types of cancer, including breast cancer, when delivered in a liposomal form. This form helps reduce side effects and targets the drug more directly to tumors, which suggests potential effectiveness for liposarcoma as well. ^{1 2 3 4 5}

Is Doxorubicin generally safe for humans?

Doxorubicin, a chemotherapy drug, is known to potentially cause muscle damage and affect bladder function, but it is widely used in cancer treatment. It is important to discuss potential side effects with your doctor. ^{6 7 8 9 10}

What makes BI 907828 different from Doxorubicin for treating liposarcoma?

BI 907828 is a novel treatment being compared to Doxorubicin, which is a well-known chemotherapy drug used for various cancers. Doxorubicin is often delivered in liposomal formulations to reduce toxicity, especially to the heart, and improve delivery to tumors. The unique aspect of BI 907828 in this trial is its potential to offer a new mechanism of action or improved efficacy and safety profile compared to the established use of Doxorubicin in cancer treatment. ^{1 5 11 12 13}

Eligibility Criteria

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 am over 18, can follow birth control guidelines if needed, and agree to the consent form.

I have a tumor that can be measured by scans.

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

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

Treatment Details

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.

Participant Groups

Group I: Brigimadlin (BI 907828) low dose Experimental Treatment 1 Intervention

Phase II

Group II: Brigimadlin (BI 907828) high dose Experimental Treatment 1 Intervention

Phase II

Group III: Brigimadlin (BI 907828) arm Experimental Treatment 1 Intervention

Phase III

Group IV: Doxorubicin arm Active Control 1 Intervention

Phase II/III

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Findings from Research

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]

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]

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]

References

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

Liposomal anthracyclines for breast cancer. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

New aspects in probucol cardioprotection against doxorubicin-induced cardiotoxicity. [2013]

3. Jamaica pubmed.ncbi.nlm.nih.gov

Anaphylaxis to pegylated liposomal Doxorubicin: a case report. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Phase I study of Doxil and vinorelbine in metastatic breast cancer. [2020]

5. England 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. [2019]

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

Comparison of cardiovascular events among treatments for overactive bladder: a Danish nationwide cohort study. [2018]

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

The Q-T interval and antimuscarinic drugs. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Cardiac effects of muscarinic receptor antagonists used for voiding dysfunction. [2021]

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

A prospective survey study of lower urinary tract dysfunction in childhood cancer survivors after vincristine and/or doxorubicin chemotherapy. [2022]

10. Japan pubmed.ncbi.nlm.nih.gov

Effect of chlorpheniramine administration on postoperative catheter-related bladder discomfort in patients undergoing transurethral excision of bladder tumor: a prospective randomized study. [2022]

11. Greece pubmed.ncbi.nlm.nih.gov

Comparison of the therapeutic efficacy of 188Rhenium-liposomes and liposomal doxorubicin in a 4T1 murine orthotopic breast cancer model. [2013]

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

In Vivo Drug Delivery Performance of Lipiodol-Based Emulsion or Drug-Eluting Beads in Patients with Hepatocellular Carcinoma. [2018]

13. New Zealand pubmed.ncbi.nlm.nih.gov

A comparison of liposomal formulations of doxorubicin with drug administered in free form: changing toxicity profiles. [2018]