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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 400
- 试验地点
- 217
- 主要终点
- Progression-free Survival (PFS)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •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
- •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.
排除标准
- •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
研究组 & 干预措施
Brigimadlin 30 mg q3w
Patients with advanced or metastatic dedifferentiated liposarcoma (DDLPS) received 30 milligram (mg) brigimadlin taken orally on day 1 of each 21-day cycle (q3w).
干预措施: Brigimadlin (Drug)
Brigimadlin 45 mg q3w
Patients with advanced or metastatic dedifferentiated liposarcoma (DDLPS) received 45 milligram (mg) brigimadlin taken orally on day 1 of each 21-day cycle (q3w).
干预措施: Brigimadlin (Drug)
Doxorubicin
Patients with advanced or metastatic dedifferentiated liposarcoma (DDLPS) received one intravenous infusion of 75 milligram per square meter (mg/m2) on Day 1 of each 21-day cycle (q3w) until a maximum cumulative dose of 450 mg/m2 (approximately 6 cycles).
干预措施: Doxorubicin (Drug)
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: Up to 20.6 months.
Progression-free survival (PFS) based on blinded central independent review. For each patient, PFS was 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. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter. (Note: the appearance of one or more new lesions is also considered progression).
次要结局
- Objective Response (OR)(Up to 20.6 months.)
- Duration of Objective Response (DOR)(Up to 20.6 months.)
- Disease Control (DC)(Up to 20.6 months.)
- Change in Health-Related Quality of Life at Week 6 and 18(Baseline (cycle 1 day 1), week 6 and week 18.)