Brightline-1: A Study to Compare Brigimadlin (BI 907828) With Doxorubicin in People With a Type of Cancer Called Dedifferentiated Liposarcoma
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| ClinicalTrials.gov Identifier: NCT05218499 |
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Recruitment Status :
Active, not recruiting
First Posted : February 1, 2022
Last Update Posted : March 29, 2024
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Liposarcoma, Dedifferentiated | Drug: Brigimadlin (BI 907828) Drug: Doxorubicin | Phase 2 Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 400 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | March 25, 2022 |
| Estimated Primary Completion Date : | April 16, 2024 |
| Estimated Study Completion Date : | May 27, 2026 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Brigimadlin (BI 907828) low dose
Phase II
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Drug: Brigimadlin (BI 907828)
Brigimadlin (BI 907828)
Other Name: Brigimadlin |
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Experimental: Brigimadlin (BI 907828) high dose
Phase II
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Drug: Brigimadlin (BI 907828)
Brigimadlin (BI 907828)
Other Name: Brigimadlin |
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Experimental: Brigimadlin (BI 907828) arm
Phase III
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Drug: Brigimadlin (BI 907828)
Brigimadlin (BI 907828)
Other Name: Brigimadlin |
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Active Comparator: Doxorubicin arm
Phase II/III
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Drug: Doxorubicin
doxorubicin |
- Progression-free survival [ Time Frame: 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.
- Objective response (OR) [ Time Frame: 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, or withdrawal of consent, whichever occurs first.
- Duration of objective response (DOR) [ Time Frame: 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) [ Time Frame: Up to 50 months ]defined as the time interval from randomization until death from any cause
- Disease control (DC) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: Up to 30 months ]
- Occurrence of treatment-emergent AEs leading to study drug discontinuation [ Time Frame: Up to 30 months ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05218499
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| Responsible Party: | Boehringer Ingelheim |
| ClinicalTrials.gov Identifier: | NCT05218499 |
| Other Study ID Numbers: |
1403-0008 2021-002392-20 ( EudraCT Number ) |
| First Posted: | February 1, 2022 Key Record Dates |
| Last Update Posted: | March 29, 2024 |
| Last Verified: | March 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Once the time frame criteria given under number 4 are fulfilled, researchers can use the following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Clinical Study Report (CSR) |
| Time Frame: | After structured results have been posted, all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication. |
| Access Criteria: | For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement. |
| URL: | https://www.mystudywindow.com/msw/datasharing |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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