Brightline-2: A Study to Test Whether Brigimadlin (BI 907828) Helps People With Cancer in the Biliary Tract, Pancreas, Lung or Bladder
- Conditions
- Pancreatic NeoplasmsLung NeoplasmsSolid TumorsBiliary Tract CancerBladder Cancer
- Interventions
- Registration Number
- NCT05512377
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
This study is open to adults with advanced cancer in the biliary tract, pancreas, lung, or bladder. This is a study for people for whom previous treatment was not successful or no treatment exists.
The purpose of this study is to find out whether a medicine called BI 907828 helps people with cancer in the biliary tract, pancreas, lung, or bladder. BI 907828 is a so-called MDM2 inhibitor that is being developed to treat cancer. All participants take BI 907828 as a tablet once every 3 weeks. Participants may continue to take BI 907828 as long as they benefit from treatment and can tolerate it. They visit the study site regularly. At the study site, doctors regularly check the size of the tumour and 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
- 99
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Diagnosis of a solid tumour which meets the criteria for an open trial cohort:
- Cohorts 1 and 1-CN (biliary tract adenocarcinoma): Locally advanced or metastatic biliary tract adenocarcinoma (intra- and extrahepatic cholangiocarcinoma, gallbladder cancer, and ampullary cancer).Patients must have unresectable disease and have received all available conventional therapies known to confer clinical benefit for their disease based on local approved standards; or (in the opinion of the investigator) patients are unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy.
- Cohort 2 (pancreatic ductal adenocarcinoma): Locally advanced or metastatic pancreatic ductal adenocarcinoma. Patients must have unresectable disease and have received all available conventional therapies known to confer clinical benefit for their disease based on local approved standards.
- Cohort 3 (lung adenocarcinoma): Locally advanced or metastatic lung adenocarcinoma. Patients must have unresectable disease and have received all available conventional therapies known to confer clinical benefit for their disease based on local approved standards.
- Cohort 4 (urothelial bladder cancer): Locally advanced or metastatic urothelial bladder cancer. Patients must have unresectable disease and have received all available conventional therapies known to confer clinical benefit for their disease based on local approved standards.
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Written pathology report / molecular profiling report indicating Mouse double minute 2 homolog (MDM2) amplification or a copy number ≥8 and tumor protein 53 (TP53) wild-type status. This must have been confirmed with a tissue-based test. A test with liquid biopsy is not accepted.
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Archival tissue (formalin fixed paraffin embedded [FFPE] tumour blocks or slides) must be provided for retrospective confirmation of MDM2 amplification and TP53 status.
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Presence of at least 1 measurable target lesion according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.
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Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
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Patient must be willing to donate mandatory blood samples for the pharmacokinetics, pharmacodynamics, and biomarker analyses
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Adequate organ function
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All toxicities related to previous anti-cancer therapies have resolved to ≤Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 prior to trial treatment administration (except for alopecia and amenorrhea / menstrual disorders which can be of any grade and peripheral neuropathy which must be ≤CTCAE Grade 2).
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Life expectancy ≥3 months at the start of treatment in the opinion of the investigator.
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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.
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Male or female patients ≥18 years old at the time of signature of the 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.
- Previous administration of brigimadlin (BI 907828) or any other MDM2-p53 or mouse double minute 4 (MDMX, MDM4)-p53 antagonist.
- Active bleeding, significant risk of haemorrhage (e.g. previous severe gastrointestinal bleeding, previous haemorrhagic stroke at any time), or current bleeding disorder (e.g. haemophilia, von Willebrand disease).
- Major surgery (major according to the investigator's assessment) performed within 4 weeks prior to start of trial treatment or planned within 6 months after screening (e.g. hip replacement).
- Clinically significant previous or concomitant malignancies in the opinion of the investigator affecting the efficacy and/or outcome of the trial.
- 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.
- Any history of, or concomitant condition that, in the opinion of the investigator, would compromise the patient's ability to comply with the trial or interfere with the evaluation of the safety and efficacy of the trial drug.
- 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
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description brigimadlin (BI 907828) treatment arm brigimadlin -
- Primary Outcome Measures
Name Time Method Objective response (OR) Up to 30 months OR is defined as a best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST version 1.1.
- Secondary Outcome Measures
Name Time Method Duration of objective response (DOR) Up to 30 months DOR is defined as the time from first documented confirmed objective response (OR) until the earliest date of disease progression or death among patients with confirmed objective response.
Progression-free survival (PFS) Up to 30 months PFS is defined as the time from treatment start until the earliest date of tumour progression according to RECIST version 1.1 or death from any cause, whichever occurs first.
Overall survival (OS) Up to 50 months OS is defined as the time from treatment start until death from any cause.
Disease control (DC) Up to 30 months DC is defined as a best overall response of CR, PR, or stable disease (SD) where best overall response is defined according to RECIST version 1.1.
Change from baseline in European Organisation for Research and Treatment (EORTC) Quality of Life Questionnaire (QLQ)-C30 physical functioning domain score Up to 30 months The QLQ-C30 comprises 30 questions. The QLQ-C30 incorporates both multi-items scales and single-item measures. These include 1 global health status/QoL scale, 5 functional scales, 3 symptoms scales and 6 single items to assess dyspnoea, insomnia, appetite loss, constipation, diarrhoea, and financial difficulties. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. 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.
Occurrence of treatment-emergent adverse events (AEs) during the on-treatment period Up to 30 months Change from baseline in EORTC QLQ-C30 fatigue domain score Up to 30 months It is part of QLQ-C30 and uses 4-point scale (1=not at all to 4=very much)
Change from baseline in EORTC QLQ-C30 role functioning domain score Up to 30 months It is part of QLQ-C30 and uses 4-point scale (1=not at all to 4=very much)
Change from baseline in EORTC QLQ-BIL21 tiredness domain score Up to 30 months The QLQ-BIL21 is specific for the assessment of quality of life in patients with cholangiocarcinoma and cancer of the gallbladder. It consists of 21 questions with a 4-point scale (1=not at all to 4=very much), and the tiredness domain is part of it.
Occurrence of treatment-emergent AEs leading to trial drug discontinuation during the on-treatment period Up to 30 months
Trial Locations
- Locations (60)
Southern Cancer Center
🇺🇸Mobile, Alabama, United States
University of Arizona
🇺🇸Tucson, Arizona, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Stanford Cancer Institute
🇺🇸Palo Alto, California, United States
Providence Medical Foundation-Santa Rosa -69764
🇺🇸Santa Rosa, California, United States
Rocky Mountain Cancer Centers-Lone Tree-69498
🇺🇸Lone Tree, Colorado, United States
Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital
🇺🇸Washington, District of Columbia, United States
Norton Cancer Institute, Downtown
🇺🇸Louisville, Kentucky, United States
University of Michigan Health System
🇺🇸Ann Arbor, Michigan, United States
Nebraska Cancer Specialists-Omaha-69066
🇺🇸Omaha, Nebraska, United States
Perlmutter Cancer Center at NYU Langone Hospital - Long Island
🇺🇸Mineola, New York, United States
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
🇺🇸New York, New York, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Oncology Associates of Oregon, PC
🇺🇸Eugene, Oregon, United States
Oregon Health and Sciences University
🇺🇸Portland, Oregon, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Prince of Wales Hospital-Randwick-66496
🇦🇺Randwick, New South Wales, Australia
ICON-South Brisbane-69267
🇦🇺South Brisbane, Queensland, Australia
Flinders Medical Centre
🇦🇺Bedford Park, South Australia, Australia
Austin Health
🇦🇺Heidelberg, Victoria, Australia
Ordensklinikum Linz GmbH - Barmherzige Schwestern
🇦🇹Linz, Austria
LK Wiener Neustadt
🇦🇹Wiener Neustadt, Austria
Edegem - UNIV UZ Antwerpen
🇧🇪Edegem, Belgium
UNIV UZ Gent
🇧🇪Gent, Belgium
CTR Georges-François Leclerc
🇫🇷Dijon, France
INS Gustave Roussy
🇫🇷Villejuif, France
Universitätsklinikum Carl Gustav Carus Dresden
🇩🇪Dresden, Germany
Krankenhaus Nordwest, Frankfurt
🇩🇪Frankfurt, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Klinikum der Universität München AÖR
🇩🇪München, Germany
Universitätsklinikum Ulm
🇩🇪Ulm, Germany
National Cancer Center Hospital East
🇯🇵Chiba, Kashiwa, Japan
Kanagawa Cancer Center
🇯🇵Kanagawa, Yokohama, Japan
Tohoku University Hospital
🇯🇵Miyagi, Sendai, Japan
Osaka International Cancer Institute
🇯🇵Osaka, Osaka, Japan
National Cancer Center Hospital
🇯🇵Tokyo, Chuo-ku, Japan
Japanese Foundation for Cancer Research
🇯🇵Tokyo, Koto-ku, Japan
Yamaguchi University Hospital
🇯🇵Yamaguchi, Ube, Japan
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
King Abdul Aziz Medical City
🇸🇦Riyadh, Saudi Arabia
National University Hospital-Singapore-42005
🇸🇬Singapore, Singapore
Rainbow Oncology
🇿🇦KwaZulu, South Africa
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Fundación Jiménez Díaz
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Clínico de Valencia
🇪🇸Valencia, Spain
University Hospital Bern/Inselspital Bern
🇨🇭Bern, Switzerland
University Hospital Geneva
🇨🇭Genève 14, Switzerland
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
China Medical University Hospital
🇨🇳Taichung, Taiwan
National Taiwan University Cancer Center
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Songklanagarind Hospital
🇹🇭Hat Yai, Thailand
Srinagarind Hospital
🇹🇭Muang, Thailand
University College Hospital
🇬🇧London, United Kingdom