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

Liposarcoma, Dedifferentiated Clinical Trial

Official title:

Brightline-1: A Phase II/III, Randomized, Open-label, Multi-center Study of Brigimadlin (BI 907828) Compared to Doxorubicin as First Line Treatment of Patients With Advanced Dedifferentiated Liposarcoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05218499
• Other study ID #: 1403-0008
• Secondary ID: 2021-002392-20
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: March 25, 2022
• Est. completion date: May 27, 2026

Study information

• Verified date: May 2024
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 400
• Est. completion date: May 27, 2026
• Est. primary completion date: April 16, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

• Further exclusion criteria apply

Related Conditions & MeSH terms

• Liposarcoma
• Liposarcoma, Dedifferentiated

Intervention

Drug:
• Brigimadlin (BI 907828)
Brigimadlin (BI 907828)
• Doxorubicin
doxorubicin

Locations

Country	Name	City	State
Australia	Ashford Cancer Centre Research	Kurralta Park	South Australia
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	Prince of Wales Hospital	Randwick	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Belgium	UZ Leuven	Leuven
Canada	Maisonneuve-Rosemont Hospital	Montreal	Quebec
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	BC Cancer Agency - Vancouver	Vancouver	British Columbia
China	Beijing Cancer Hospital	Beijing
China	Cancer Hospital of Chinese Academy of Medical Science	Beijing
China	The First Hospital of Jilin University	Changchun
China	West China Hospital	Chengdu
China	Sun Yat-Sen University Cancer Center	Guangzhou
China	Harbin Medical University cancer hospital	Haerbin
China	Zhejiang Cancer Hospital	Hangzhou
China	Zhongshan Hospital Fudan University	Shanghai
China	Wuhan Union Hospital	Wuhan
Czechia	Masaryk Memorial Cancer Institute	Brno
Czechia	University Hospital Olomouc	Olomouc
Czechia	University Hospital Motol	Prague 5
Denmark	Herlev and Gentofte Hospital	Herlev
Finland	HUCH Comprehensive Cancer Center, building 2	Helsinki
Finland	Tampere University Hospital	Tampere
France	INS Bergonie	Bordeaux
France	CTR Oscar Lambret	Lille
France	CTR Leon Berard	Lyon
France	HOP Timone	Marseille
France	HOP Cochin	Paris
France	CTR Eugène Marquis	Rennes
France	INS Claudius Regaud IUCT-Oncopole	Toulouse
France	INS Gustave Roussy	Villejuif
Germany	Helios Klinikum Bad Saarow	Bad Saarow
Germany	Helios Klinikum Berlin-Buch	Berlin
Germany	Universitätsklinikum Carl Gustav Carus Dresden	Dresden
Germany	Universitätsklinikum Essen AöR	Essen
Germany	Asklepios Kliniken GmbH & Co. KGaA	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitätsklinikum Mannheim GmbH	Mannheim
Germany	Klinikum der Universität München AÖR	München
Germany	Robert Bosch Gesellschaft für medizinische Forschung mbH	Stuttgart
Greece	Hippokration General Hospital of Athen	Athens
Greece	"Attikon" University General Hospital of Attica	Haidari
Greece	Bioclinic Thessaloniki	Thessaloniki
Hong Kong	Prince of Wales Hospital	Hong Kong
Italy	Humanitas Gavazzeni	Bergamo
Italy	Istituto Di Candiolo	Candiolo (TO)
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	Istituto Nazionale IRCCS Tumori Fondazione Pascale	Napoli
Italy	AOU San Luigi Gonzaga	Orbassano (TO)
Italy	Istituto Oncologico Veneto IRCCS	Padova
Italy	A.O. Univ. Policlinico Giaccone	Palermo
Italy	Università Campus Bio-Medico - ROMA	Roma
Japan	Aichi Cancer Center Hospital	Aichi, Nagoya
Japan	Nagoya University Hospital	Aichi, Nagoya
Japan	National Cancer Center Hospital East	Chiba, Kashiwa
Japan	Kyushu University Hospital	Fukuoka, Fukuoka
Japan	National Hospital Organization Kyushu Cancer Center	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
Netherlands	Nederlands Kanker Instituut	Amsterdam
Netherlands	Leids Universitair Medisch Centrum (LUMC)	Leiden
Norway	Oslo Universitetssykehus HF, Radiumhospitalet	Oslo
Portugal	IPO Lisboa Francisco Gentil, EPE	Lisboa
Portugal	ULS de Santa Maria, E.P.E	Lisboa
Spain	Hospital Santa Creu i Sant Pau	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Duran i Reynals	L'Hospitalet de Llobregat
Spain	Fundación Jiménez Díaz	Madrid
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital La Paz	Madrid
Spain	Hospital Universitario HM Sanchinarro	Madrid
Spain	Hospital Virgen de la Victoria	Malaga
Spain	Hospital Clínico de Santiago	Santiago de Compostela
Spain	Hospital Miguel Servet	Zaragoza
Sweden	Skånes universitetssjukhus	Lund
Sweden	Karolinska Universitetssjukhuset Stockholm	Stockholm
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
United Kingdom	Addenbrooke's Hospital	Cambridge
United Kingdom	Churchill Hospital	Headington
United Kingdom	The Royal Marsden Hospital, Chelsea	London
United Kingdom	University College Hospital	London
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	Winship Cancer Institute	Atlanta	Georgia
United States	Precision NextGen Oncology	Beverly Hills	California
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University Hospitals of Cleveland	Cleveland	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	City of Hope	Duarte	California
United States	Mayo Clinic Cancer Center	Jacksonville	Florida
United States	University of Southern California	Los Angeles	California
United States	Froedtert and The Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Henry-Joyce Cancer Clinic	Nashville	Tennessee
United States	Nebraska Cancer Specialists	Omaha	Nebraska
United States	Oregon Health and Sciences University	Portland	Oregon
United States	Mayo Clinic, Rochester	Rochester	Minnesota
United States	Barnes-Jewish Hospital	Saint Louis	Missouri
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Sarcoma Oncology Center	Santa Monica	California
United States	University of Arizona	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  China,  Czechia,  Denmark,  Finland,  France,  Germany,  Greece,  Hong Kong,  Italy,  Japan,  Netherlands,  Norway,  Portugal,  Spain,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival	defined as the time interval from randomization until tumor progression according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (solely based on blinded central independent review) or death from any cause, whichever occurs first.	Up to 30 months
Secondary	Objective response (OR)	defined as a best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST version 1.1 (based on blinded central independent review) from the date of randomization until disease progression, death, or last evaluable tumor assessment before start of subsequent anti-cancer therapy, loss to follow-up, or withdrawal of consent, whichever occurs first.	Up to 30 months
Secondary	Duration of objective response (DOR)	defined as the time interval from first documented confirmed OR until disease progression or death among patients with confirmed objective response (based on blinded central independent review), whichever occurs first.	Up to 30 months
Secondary	Overall survival (OS)	defined as the time interval from randomization until death from any cause	Up to 50 months
Secondary	Disease control (DC)	defined as a best overall response of CR, PR, or stable disease (SD) according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 (based on blinded central independent review).	Up to 30 months
Secondary	Change from baseline in QLQ-C30 (Quality of Life questionnaire C30)	The QLQ C30 rates the overall quality of life in cancer participants. 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function, symptoms and financial difficulties and 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Includes scores for physical functioning, fatigue, pain, global health status.	Up to week 18
Secondary	Change from baseline in EQ-5D5L (European Quality of Life 5 dimensions 5 level)	The EQ-5D-5L is a standardized instrument to assess of health outcome through 5 Likert scale items. In the EQ-5D-5L VAS, the participant rates his or her general state of health at the time of the assessment on a scale from 0 to 100.	Up to week 18
Secondary	Change from baseline in fatigue	Fatigue symptoms are assessed through 25 items selected from the European Organization for Research and Treatment of Cancer (EORTC) item library. Items use a 4-point scale (1=not at all to 4=very much) similar to the C30.	Up to week 18
Secondary	Change from baseline in pain	Pain symptoms are assessed through 18 items selected from the EORTC item library. Items use a 4-point scale (1=not at all to 4=very much) similar to the C30.	Up to week 18
Secondary	Occurrence of treatment-emergent adverse events (AEs)		Up to 30 months
Secondary	Occurrence of treatment-emergent AEs leading to study drug discontinuation		Up to 30 months

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