Advanced dedifferentiated liposarcoma MedDRA version: 20.0 Level: PT Classification code 10073135 Term: Dedifferentiated liposarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Boehringer Ingelheim SComm
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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. 2. Male or female patients =18 years old at the time of signature of the ICF. Women of childbearing potential 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. 3. Histologically proven locally advanced or metastatic, unresectable (surgery morbidity would outweigh potential benefits), progressive or recurrent 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. 4. Written pathology report indicating the diagnosis of DDLPS with positive MDM2 immunohistochemistry or MDM2 amplification as demonstrated by fluorescence in situ hybridization or NGS must be available. 5. Formalin fixed paraffin embedded tumor blocks or slides must be available for retrospective histopathological central review. 6. Presence of at least one measurable target lesion according to 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. 7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. 8. Patient must be willing to donate blood samples for the pharmacokinetics, pharmacodynamics, and tumor mutation analysis. 9. Patient willing to undergo a mandatory tumor biopsy at the time point specified in the flowchart unless exempt. 10. Adequate organ function Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 195 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 195
Exclusion criteria
Exclusion criteria: 1. Known mutation in the TP53 gene (screening for TP53 status is not required). 2. Major surgery (major according to the investigator’s assessment) performed within 4 weeks prior to randomization or planned within 6 months after screening. 3. Prior systemic therapy for liposarcoma in any setting (including adjuvant, neoadjuvant, maintenance, palliative). 4. 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. 5. 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). 6. 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. 7. 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). 8. 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 criteria apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The trial will assess the efficacy and safety of brigimadlin compared to doxorubicin as first line systemic therapy for advanced or metastatic DDLPS.;Secondary Objective: The secondary objectives of the Phase II part of the trial are to select an optimal dose of brigimadlin and to evaluate prior to the Phase III part whether the expected benefits of brigimadlin as first line systemic therapy for advanced or metastatic DDLPS outweigh any risks. The secondary objectives of the Phase III part of the trial are to evaluate whether brigimadlin as first line systemic therapy for advanced or metastatic DDLPS improves the objective response rate, duration of responses, overall survival, disease control rate, tolerability and delays worsening of quality of life, compared to doxorubicin. Safety of brigimadlin will be investigated in both parts of the trial. ;Primary end point(s): Progression-free survival (PFS);Timepoint(s) of evaluation of this end point: 1) 13 and 21 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Objective response (OR) 2) Duration of objective response (DOR) 3) Overall survival (OS) 4) Disease control (DC) 5) Health-Related Quality of Life (HRQoL) 6) Occurrence of the trialtreatment-emergent adverse events (AEs). 7) Occurrence of treatment-emergent AEs leading to study drug discontinuation;Timepoint(s) of evaluation of this end point: 1) 13 and 21 months 2) 13 and 21 months 3) 13 and 21 months 4) 13 and 21 months 5) 13 and 21 months 6) 13 and 21 months 7) 13 and 21 months | — |
Countries
Australia, Belgium, Canada, China, Czechia, Czech Republic, Denmark, Finland, France, Germany, Greece, Hong Kong, Ireland, Italy, Japan, Korea, Republic of, Netherlands, Norway, Portugal, Spain, Sweden, Taiwan, Türkiye, United Kingdom, United States
Contacts
Public ContactCT Disclosure & Data Transparency
Boehringer Ingelheim Pharma GmbH & Co. KG
Outcome results
None listed