Clinical trial NCT05218499: Brightline-1: A Study to Compare Brigimadlin (BI 907828) With Doxorubicin in People With a Type of Cancer Called Dedifferentiated Liposarcoma
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Liposarcoma, Dedifferentiated
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2022-02-01
Enrollment: 401
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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).
* Further exclusion criteria apply

Primary outcomes:
measure: Progression-free survival
timeFrame: Up to 30 months
Secondary outcomes:
measure: Objective response (OR)
timeFrame: Up to 30 months
measure: Duration of objective response (DOR)
timeFrame: Up to 30 months
measure: Overall survival (OS)
timeFrame: Up to 50 months
measure: Disease control (DC)
timeFrame: Up to 30 months
measure: Change from baseline in QLQ-C30 (Quality of Life questionnaire C30)
timeFrame: Up to week 18
measure: Change from baseline in EQ-5D5L (European Quality of Life 5 dimensions 5 level)
timeFrame: Up to week 18
measure: Change from baseline in fatigue
timeFrame: Up to week 18
measure: Change from baseline in pain
timeFrame: Up to week 18
measure: Occurrence of treatment-emergent adverse events (AEs)
timeFrame: Up to 30 months
measure: Occurrence of treatment-emergent AEs leading to study drug discontinuation
timeFrame: Up to 30 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Beverly Hills
country: United States
facility: Precision NextGen Oncology
state: California
city: Duarte
country: United States
facility: City of Hope-Duarte-56419
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Santa Monica
country: United States
facility: Sarcoma Oncology Center
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute
state: Georgia
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic, Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Omaha
country: United States
facility: Nebraska Cancer Specialists-Omaha-69502
state: Nebraska
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Sciences University
state: Oregon
city: Nashville
country: United States
facility: Henry-Joyce Cancer Clinic
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Milwaukee
country: United States
facility: Froedtert and The Medical College of Wisconsin
state: Wisconsin
city: Randwick
country: Australia
facility: Prince of Wales Hospital-Randwick-66496
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Kurralta Park
country: Australia
facility: Ashford Cancer Centre Research
state: South Australia
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Leuven
country: Belgium
facility: UZ Leuven
city: Vancouver
country: Canada
facility: BC Cancer Agency - Vancouver
state: British Columbia
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Maisonneuve-Rosemont Hospital
state: Quebec
city: Beijing
country: China
facility: Cancer Hospital of Chinese Academy of Medical Science
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Changchun
country: China
facility: The First Hospital of Jilin University
city: Chengdu
country: China
facility: West China Hospital
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Shanghai
country: China
facility: Zhongshan Hospital Affiliated to Fudan University
city: Wuhan
country: China
facility: Wuhan Union Hospital
city: Brno
country: Czechia
facility: Masaryk Memorial Cancer Institute
city: Olomouc
country: Czechia
facility: University Hospital Olomouc
city: Prague 5
country: Czechia
facility: University Hospital Motol
city: Herlev
country: Denmark
facility: Herlev and Gentofte Hospital
city: Helsinki
country: Finland
facility: HUCH Comprehensive Cancer Center, building 2
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Bordeaux
country: France
facility: INS Bergonie
city: Lille
country: France
facility: CTR Oscar Lambret
city: Lyon
country: France
facility: CTR Leon Berard
city: Marseille
country: France
facility: HOP Timone
city: Paris
country: France
facility: HOP Cochin
city: Rennes
country: France
facility: CTR Eugène Marquis
city: Toulouse
country: France
facility: INS Claudius Regaud IUCT-Oncopole
city: Villejuif
country: France
facility: INS Gustave Roussy
city: Bad Saarow
country: Germany
facility: Helios Klinikum Bad Saarow
city: Berlin
country: Germany
facility: Helios Klinikum Berlin-Buch
city: Dresden
country: Germany
facility: Technische Universität Dresden
city: Essen
country: Germany
facility: Universitätsklinikum Essen AöR
city: Hamburg
country: Germany
facility: Asklepios Kliniken GmbH & Co. KGaA
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Mannheim
country: Germany
facility: Universitätsklinikum Mannheim GmbH
city: München
country: Germany
facility: Klinikum der Universität München AÖR
city: Stuttgart
country: Germany
facility: Robert Bosch Gesellschaft für medizinische Forschung mbH
city: Athens
country: Greece
facility: Hippokration General Hospital of Athen
city: Haidari
country: Greece
facility: "Attikon" University General Hospital of Attica
city: Thessaloniki
country: Greece
facility: Bioclinic Thessaloniki
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital-Hong Kong-20715
city: Bergamo
country: Italy
facility: Humanitas Gavazzeni
city: Candiolo (TO)
country: Italy
facility: Istituto Di Candiolo
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Napoli
country: Italy
facility: Istituto Nazionale IRCCS Tumori Fondazione Pascale
city: Orbassano (TO)
country: Italy
facility: AOU San Luigi Gonzaga
city: Padova
country: Italy
facility: Istituto Oncologico Veneto IRCCS
city: Palermo
country: Italy
facility: A.O. Univ. Policlinico Giaccone
city: Roma
country: Italy
facility: Università Campus Bio-Medico - ROMA
city: Aichi, Nagoya
country: Japan
facility: Aichi Cancer Center Hospital
city: Aichi, Nagoya
country: Japan
facility: Nagoya University Hospital
city: Chiba, Kashiwa
country: Japan
facility: National Cancer Center Hospital East
city: Fukuoka, Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Fukuoka, Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Miyagi, Sendai
country: Japan
facility: Tohoku University Hospital
city: Okayama, Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka, Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Sapporo, Hokkaido
country: Japan
facility: Hokkaido Cancer Center
city: Tokyo, Chuo-ku
country: Japan
facility: National Cancer Center Hospital
city: Tokyo, Koto-ku
country: Japan
facility: Japanese Foundation for Cancer Research
city: Amsterdam
country: Netherlands
facility: Nederlands Kanker Instituut
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum (LUMC)
city: Oslo
country: Norway
facility: Oslo Universitetssykehus HF, Radiumhospitalet
city: Lisboa
country: Portugal
facility: IPO Lisboa Francisco Gentil, EPE
city: Lisboa
country: Portugal
facility: ULS de Santa Maria, E.P.E
city: Barcelona
country: Spain
facility: Hospital Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: L'Hospitalet de Llobregat
country: Spain
facility: Hospital Duran i Reynals
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital La Paz
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
city: Malaga
country: Spain
facility: Hospital Virgen de la Victoria
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico de Santiago
city: Zaragoza
country: Spain
facility: Hospital Miguel Servet
city: Lund
country: Sweden
facility: Skånes universitetssjukhus
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset Stockholm
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: Headington
country: United Kingdom
facility: Churchill Hospital
city: London
country: United Kingdom
facility: University College Hospital
city: London
country: United Kingdom
facility: The Royal Marsden Hospital, Chelsea
Study officials:
References: