Brightline-1: A Study to Compare Brigimadlin (BI 907828) With Doxorubicin in People With a Type of Cancer Called Dedifferentiated Liposarcoma

NCT ID: NCT05218499

Last Updated: 2025-11-14

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-31
• Study Completion Date: 2025-11-28

Brief Summary

This study is open to people with a type of cancer called dedifferentiated liposarcoma. People with advanced liposarcoma aged 18 or older who are not receiving any other cancer treatment can participate.

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 so-called MDM2 inhibitor that is being developed to treat cancer. Doxorubicin is a medicine already used to treat cancer including liposarcoma.

During the study, participants get either brigimadlin (BI 907828) or doxorubicin. Every 3 weeks, participants take brigimadlin (BI 907828) as tablets or doxorubicin as an infusion into a vein. Participants can switch to brigimadlin (BI 907828) treatment if they did not benefit from doxorubicin treatment.

Participants can continue treatment in the study as long as they benefit from it and can tolerate it.

Doctors regularly check the size of the tumour and check whether it has spread to other parts of the body. The doctors also regularly check participants' health and take note of any unwanted effects.

Conditions

Liposarcoma, Dedifferentiated

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Brigimadlin 30 mg q3w

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 Type: EXPERIMENTAL

Brigimadlin

Intervention Type: DRUG

Brigimadlin taken orally on day 1 of each 21-day cycle (q3w).

Brigimadlin 45 mg q3w

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 Type: EXPERIMENTAL

Brigimadlin

Intervention Type: DRUG

Brigimadlin taken orally on day 1 of each 21-day cycle (q3w).

Doxorubicin

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).

Group Type: ACTIVE_COMPARATOR

Doxorubicin

Intervention Type: DRUG

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).

Interventions

Brigimadlin

Brigimadlin taken orally on day 1 of each 21-day cycle (q3w).

Intervention Type: DRUG

Doxorubicin

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).

Intervention Type: DRUG

Other Intervention Names

BI 907828

Eligibility Criteria

Inclusion Criteria

• Provision of signed and dated, written informed consent form (ICF) in accordance with ICH-GCP and local legislation prior to any trial-specific procedures, sampling, or analyses.
• Male or female patients ≥18 years old at the time of signature of the informed consent form (ICF). Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use 2 medically acceptable methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly beginning at screening, during trial participation, and until 6 months and 12 days after last dose for women and 102 days after last dose for men. A list of contraception methods meeting these criteria is provided in the patient information.
• Histologically proven locally advanced or metastatic, unresectable (surgery morbidity would outweigh potential benefits), progressive or recurrent dedifferentiated liposarcoma (DDLPS). Locally performed histopathological diagnosis will be accepted for entry into this trial but will be confirmed by independent pathological review while the patients receive treatment in this trial.
• 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.
• Presence of at least one measurable target lesion according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. In patients who only have one target lesion, the baseline imaging must be performed at least 2 weeks after any biopsy of the target lesion.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Patient must be willing to donate blood samples for the pharmacokinetics, pharmacodynamics, and tumor mutation analysis.
• Patient willing to undergo a mandatory tumor biopsy at the time point specified in the flowchart unless exempt.
• Adequate organ function.

Exclusion Criteria

• 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.
• Prior systemic therapy for liposarcoma in any setting (including adjuvant, neoadjuvant, maintenance, palliative).
• Previous or concomitant malignancies other than DDLPS or WDLPS, treated within the previous 5 years, except effectively treated non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ, or other malignancy that is considered cured by local treatment.
• Previous treatment with anthracyclines in any setting (systemic treatment with other anticancer agents is allowed if completed at least 5 years prior to study entry with the exception of hormone therapy).
• Patients who must or intend to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial.
• Currently enrolled in another investigational device or drug trial, or less than 30 days since ending another investigational device or drug trial(s) or receiving other investigational treatment(s).
• Patients not expected to comply with the protocol requirements or not expected to complete the trial as scheduled (e.g. chronic alcohol or drug abuse or any other condition that, in the investigator's opinion, makes the patient an unreliable trial participant).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

University of Arizona

Tucson, Arizona, United States

Precision NextGen Oncology

Beverly Hills, California, United States

City of Hope-Duarte-56419

Duarte, California, United States

University of Southern California

Los Angeles, California, United States

Sarcoma Oncology Center

Santa Monica, California, United States

Mayo Clinic Cancer Center

Jacksonville, Florida, United States

Winship Cancer Institute

Atlanta, Georgia, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

University of Michigan Health System

Ann Arbor, Michigan, United States

Mayo Clinic, Rochester

Rochester, Minnesota, United States

Barnes-Jewish Hospital

St Louis, Missouri, United States

Nebraska Cancer Specialists-Omaha-69502

Omaha, Nebraska, United States

University Hospitals of Cleveland

Cleveland, Ohio, United States

Oregon Health and Sciences University

Portland, Oregon, United States

Henry-Joyce Cancer Clinic

Nashville, Tennessee, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Froedtert and The Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Prince of Wales Hospital-Randwick-66496

Randwick, New South Wales, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Ashford Cancer Centre Research

Kurralta Park, South Australia, Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

UZ Leuven

Leuven, , Belgium

BC Cancer Agency - Vancouver

Vancouver, British Columbia, Canada

The Ottawa Hospital

Ottawa, Ontario, Canada

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Maisonneuve-Rosemont Hospital

Montreal, Quebec, Canada

Cancer Hospital of Chinese Academy of Medical Science

Beijing, , China

Beijing Cancer Hospital

Beijing, , China

The First Hospital of Jilin University

Changchun, , China

West China Hospital of Sichuan University

Chengdu, , China

Sun Yat-Sen University Cancer Center

Guangzhou, , China

Zhejiang Cancer Hospital

Hangzhou, , China

Harbin Medical University Cancer Hospital

Harbin, , China

Zhongshan Hospital Affiliated to Fudan University

Shanghai, , China

Wuhan Union Hospital

Wuhan, , China

Masaryk Memorial Cancer Institute

Brno, , Czechia

University Hospital Olomouc

Olomouc, , Czechia

Motol University Hospital

Prague, , Czechia

Herlev and Gentofte Hospital

Herlev, , Denmark

HUCH Comprehensive Cancer Center, building 2

Helsinki, , Finland

Tampere University Hospital

Tampere, , Finland

INS Bergonie

Bordeaux, , France

CTR Oscar Lambret

Lille, , France

CTR Leon Berard

Lyon, , France

HOP Timone

Marseille, , France

Hôpital Cochin

Paris, , France

CTR Eugène Marquis

Rennes, , France

INS Claudius Regaud IUCT-Oncopole

Toulouse, , France

INS Gustave Roussy

Villejuif, , France

Helios Klinikum Bad Saarow

Bad Saarow, , Germany

Helios Klinikum Berlin-Buch

Berlin, , Germany

Technische Universität Dresden

Dresden, , Germany

Universitätsklinikum Essen AöR

Essen, , Germany

Asklepios Kliniken GmbH & Co. KGaA

Hamburg, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Universitätsklinikum Mannheim GmbH

Mannheim, , Germany

Klinikum der Universität München AÖR

München, , Germany

Robert Bosch Gesellschaft für medizinische Forschung mbH

Stuttgart, , Germany

Hippokration General Hospital of Athen

Athens, , Greece

"Attikon" University General Hospital of Attica

Haidari, , Greece

Bioclinic Thessaloniki

Thessaloniki, , Greece

Prince of Wales Hospital-Hong Kong-20715

Hong Kong, , Hong Kong

Humanitas Gavazzeni

Bergamo, , Italy

Istituto Di Candiolo

Candiolo (TO), , Italy

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

Istituto Nazionale IRCCS Tumori Fondazione Pascale

Napoli, , Italy

AOU San Luigi Gonzaga

Orbassano (TO), , Italy

Istituto Oncologico Veneto IRCCS

Padua, , Italy

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

Palermo, , Italy

Università Campus Bio-Medico - ROMA

Roma, , Italy

Aichi Cancer Center Hospital

Aichi, Nagoya, , Japan

Nagoya University Hospital

Aichi, Nagoya, , Japan

National Cancer Center Hospital East

Chiba, Kashiwa, , Japan

National Hospital Organization Kyushu Cancer Center

Fukuoka, Fukuoka, , Japan

Kyushu University Hospital

Fukuoka, Fukuoka, , Japan

Tohoku University Hospital

Miyagi, Sendai, , Japan

Okayama University Hospital

Okayama, Okayama, , Japan

Osaka International Cancer Institute

Osaka, Osaka, , Japan

Hokkaido Cancer Center

Sapporo, Hokkaido, , Japan

National Cancer Center Hospital

Tokyo, Chuo-ku, , Japan

Japanese Foundation for Cancer Research

Tokyo, Koto-ku, , Japan

Nederlands Kanker Instituut

Amsterdam, , Netherlands

Leids Universitair Medisch Centrum (LUMC)

Leiden, , Netherlands

Oslo Universitetssykehus HF, Radiumhospitalet

Oslo, , Norway

IPO Lisboa Francisco Gentil, EPE

Lisbon, , Portugal

ULS de Santa Maria, E.P.E

Lisbon, , Portugal

Hospital Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Universitari Vall D Hebron

Barcelona, , Spain

Hospital Duran i Reynals

L'Hospitalet de Llobregat, , Spain

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Fundación Jiménez Díaz

Madrid, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Universitario HM Sanchinarro

Madrid, , Spain

Hospital Virgen de la Victoria

Málaga, , Spain

Hospital Clínico de Santiago

Santiago de Compostela, , Spain

Hospital Miguel Servet

Zaragoza, , Spain

Skånes universitetssjukhus

Lund, , Sweden

Karolinska Universitetssjukhuset Stockholm

Stockholm, , Sweden

National Taiwan University Hospital

Taipei, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Abdurrahman Yurtaslan Oncology Training and Research Hospital

Ankara, , Turkey (Türkiye)

Addenbrooke's Hospital

Cambridge, , United Kingdom

Velindre Cancer Centre

Cardiff, , United Kingdom

Churchill Hospital

Headington, , United Kingdom

University College Hospital

London, , United Kingdom

The Royal Marsden Hospital, Chelsea

London, , United Kingdom

Countries

Ireland; Philippines; Russia; South Korea; United States; Australia; Belgium; Canada; China; Czechia; Denmark; Finland; France; Germany; Greece; Hong Kong; Italy; Japan; Netherlands; Norway; Portugal; Spain; Sweden; Taiwan; Turkey (Türkiye); United Kingdom

References

Schoffski P, Lahmar M, Lucarelli A, Maki RG. Brightline-1: phase II/III trial of the MDM2-p53 antagonist BI 907828 versus doxorubicin in patients with advanced DDLPS. Future Oncol. 2023 Mar;19(9):621-629. doi: 10.2217/fon-2022-1291. Epub 2023 Mar 29.

Reference Type: DERIVED

PMID: 36987836 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.mystudywindow.com

Related Info

Other Identifiers

2021-002392-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1403-0008

Identifier Type: -

Identifier Source: org_study_id