Brightline-1: A Study to Compare Brigimadlin (BI 907828) With Doxorubicin in People With a Type of Cancer Called Dedifferentiated Liposarcoma
- Conditions
- Liposarcoma, Dedifferentiated
- Interventions
- Registration Number
- NCT05218499
- Lead Sponsor
- Boehringer Ingelheim
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 401
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Brigimadlin (BI 907828) arm Brigimadlin (BI 907828) Phase III Brigimadlin (BI 907828) low dose Brigimadlin (BI 907828) Phase II Brigimadlin (BI 907828) high dose Brigimadlin (BI 907828) Phase II Doxorubicin arm Doxorubicin Phase II/III
- Primary Outcome Measures
Name Time Method Progression-free survival Up to 30 months 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.
- Secondary Outcome Measures
Name Time Method Objective response (OR) Up to 30 months 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, withdrawal of consent, or end of patient's participation in the trial, whichever occurs first.
Duration of objective response (DOR) Up to 30 months 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.
Overall survival (OS) Up to 50 months defined as the time interval from randomization until death from any cause
Disease control (DC) Up to 30 months 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).
Change from baseline in QLQ-C30 (Quality of Life questionnaire C30) Up to week 18 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.
Change from baseline in EQ-5D5L (European Quality of Life 5 dimensions 5 level) Up to week 18 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.
Change from baseline in fatigue Up to week 18 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.
Change from baseline in pain Up to week 18 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.
Occurrence of treatment-emergent adverse events (AEs) Up to 30 months Occurrence of treatment-emergent AEs leading to study drug discontinuation Up to 30 months
Trial Locations
- Locations (108)
A.O. Univ. Policlinico Giaccone
🇮🇹Palermo, Italy
Helios Klinikum Berlin-Buch
🇩🇪Berlin, Germany
National Cancer Center Hospital East
🇯🇵Chiba, Kashiwa, Japan
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
🇺🇸Saint 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
🇨🇳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
University Hospital Motol
🇨🇿Prague 5, 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
HOP 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
Technische Universität 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, Germany
Hippokration General Hospital of Athen
🇬🇷Athens, Greece
"Attikon" University General Hospital of Attica
🇬🇷Haidari, Greece
Istituto Oncologico Veneto IRCCS
🇮🇹Padova, Italy
IPO Lisboa Francisco Gentil, EPE
🇵🇹Lisboa, Portugal
Hospital Duran i Reynals
🇪🇸L'Hospitalet de Llobregat, Spain
Hospital General Universitario Gregorio Marañón
🇪🇸Madrid, Spain
Fundación Jiménez Díaz
🇪🇸Madrid, Spain
Hospital La Paz
🇪🇸Madrid, Spain
Bioclinic Thessaloniki
🇬🇷Thessaloniki, Greece
Prince of Wales Hospital-Hong Kong-20715
🇭🇰Hong Kong, Hong Kong
Humanitas Gavazzeni
🇮🇹Bergamo, Italy
AOU San Luigi Gonzaga
🇮🇹Orbassano (TO), Italy
Istituto Di Candiolo
🇮🇹Candiolo (TO), Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Italy
Istituto Nazionale IRCCS Tumori Fondazione Pascale
🇮🇹Napoli, Italy
Osaka International Cancer Institute
🇯🇵Osaka, Osaka, Japan
Hokkaido Cancer Center
🇯🇵Sapporo, Hokkaido, Japan
Japanese Foundation for Cancer Research
🇯🇵Tokyo, Koto-ku, Japan
Oslo Universitetssykehus HF, Radiumhospitalet
🇳🇴Oslo, Norway
ULS de Santa Maria, E.P.E
🇵🇹Lisboa, Portugal
Università Campus Bio-Medico - ROMA
🇮🇹Roma, Italy
Aichi Cancer Center Hospital
🇯🇵Aichi, Nagoya, Japan
Nagoya University Hospital
🇯🇵Aichi, Nagoya, Japan
Tohoku University Hospital
🇯🇵Miyagi, Sendai, Japan
Okayama University Hospital
🇯🇵Okayama, Okayama, Japan
National Hospital Organization Kyushu Cancer Center
🇯🇵Fukuoka, Fukuoka, Japan
Kyushu University Hospital
🇯🇵Fukuoka, Fukuoka, Japan
National Cancer Center Hospital
🇯🇵Tokyo, Chuo-ku, Japan
Nederlands Kanker Instituut
🇳🇱Amsterdam, Netherlands
Leids Universitair Medisch Centrum (LUMC)
🇳🇱Leiden, Netherlands
Hospital Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Vall d'Hebron
🇪🇸Barcelona, 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, Spain
Skånes universitetssjukhus
🇸🇪Lund, Sweden
Karolinska Universitetssjukhuset Stockholm
🇸🇪Stockholm, Sweden
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
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