Neoplasms

All Conditions

Rare Diseases

Liposarcoma

Neoplasms, Adipose Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Sarcoma

Soft Tissue Sarcoma

Brigimadlin

Boehringer Ingelheim

This study is open to adults with a type of cancer called dedifferentiated liposarcoma (DDLPS). They can join the study if their tumours are positive for MDM2. The purpose of this study is to find out whether a medicine called brigimadlin (BI 907828) is tolerated by and helps people with DDLPS. Brigimadlin is a so-called MDM2 inhibitor that is being developed to treat cancer.

Participants take brigimadlin as a tablet once every 3 weeks. Participants may continue to take brigimadlin as long as they benefit from treatment and can tolerate it. They visit the study site regularly. At the study site, doctors regularly check participants' health and take note of any unwanted effects. The doctors also regularly check tumour size.

Brightline-4: A Study to Test How Well Brigimadlin is Tolerated by People With a Type of Cancer Called Dedifferentiated Liposarcoma

Brightline-4: A Phase III Open-label, Single-arm, Multi-center Study to Assess the Safety and Efficacy of Brigimadlin (BI 907828) Treatment in Patients With Treatment-naïve or Pre-treated Advanced Dedifferentiated Liposarcoma

Once the criteria in section "Time Frame" 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.

OR is defined as a best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (based on investigator assessment) from the date of treatment start until the earliest date of disease progression, death, or last evaluable tumour assessment before start of subsequent anticancer therapy, lost to follow-up, or withdrawal of consent

PFS is defined as the time from treatment start until the earliest date of tumour progression according to RECIST version 1.1, based on investigator assessment, or death from any cause

OS is defined as the time from treatment start until death from any cause

DOR is defined as the time from first documented confirmed OR until the earliest date of disease progression or death among patients with confirmed OR (based on investigator assessment)

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 based on investigator assessment

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Brigimadlin (BI 907828)

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.

Brightline-1: A Study to Compare Brigimadlin (BI 907828) With Doxorubicin in People With a Type of Cancer Called Dedifferentiated Liposarcoma

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

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.

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.

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.

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.

defined as the time interval from randomization until death from any cause

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).

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.

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.

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.

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.

Liposarcoma, Myxoid

Myxoid Liposarcoma

Hypoglycemic Agents

Pioglitazone

Trabectedin

Antineoplastic Agents, Alkylating

Alkylating Agents

Trabectedin administered at a dose of 1.5 mg/m2-1.3 mg/m2 (according to investigator's choice, with a top-dose of 2.6 total mg per cycle) as a 24-hour continuous infusion via a central venous access every 3 weeks and Pioglitazone given continuously at the daily dose of 45 mg by oral route. Since Trabectedin has no cumulative toxicities, and Pioglitazone as well, the combination will be administered until progressive disease, major toxicity, patient's intolerance or unwillingness to continue treatment, or medical decision by the responsible physician.

Patients will be treated with Trabectedin administered at a dose of 1.5 mg/m2-1.3 mg/m2 (according to investigator's choice, with a top-dose of 2.6 total mg per cycle) as a 24-hour continuous infusion via a central venous access every 3 weeks and pioglitazone given continuously at the daily dose of 45 mg by oral route.

Pioglitazone Oral Product

Roberta Sanfilippo, MD

Valter Torri, MD

Maurizio D'Incalci, MD

Irene De Simone

This is a phase 2 study conducted in two sequential stages:

The first stage is an Italian single institution, single arm, pilot study, aimed at exploring the activity of the combination T and P in myxoid liposarcoma patients who achieved a stable disease after a minimum of 4 cycles of T alone. If a minimum required activity will be demonstrated from the first stage, the second stage of the study will be conducted;otherwise, the study will be stopped. The second stage is an Italian open-label, multicenter, randomized, double arm, phase II trial, aimed at evaluating the combination of T and P in myxoid liposarcoma and G1 or G2 dedifferentiated liposarcomas compared to the standard treatment with T alone. Patients will be randomized with a 1:1 ratio to treatments arms as specified below:

* Control arm (A): T alone
* Experimental arm (B): T in combination with P

In the specific the first stage will be an Italian mono-institutional, single arm, pilot study exploring the activity of the combination of T and P in myxoid liposarcoma patients who achieved a stable disease after a minimum of 4 cycles of T alone. If a minimum required activity will be demonstrated from the first stage, the second stage of the study will be conducted; otherwise, the study will be stopped.

The second stage will be an Italian multicenter, open-label, randomized, double arm, phase II trial, aimed at evaluating the combination of T and P in myxoid liposarcoma and G1 or G2 dedifferentiated liposarcomas compared to the standard treatment. Patients will be randomized by a centralized computer system with a 1:1 ratio to one of the following two arms:

* Control arm (A): T alone
* Experimental arm (B): T in combination with P The pilot study will be conducted in Italy at Istituto Nazionale Tumori Milano in order to recruit 10 evaluable patients. The second stage will be conducted in approximately 10 italian centers in order to recruit 80 evaluable patients.

Study on Trabectedin in Combination With Pioglitazone in Patients Myxoid Liposarcomas With Stable Disease After T Alone.

A Phase II Study on Trabectedin in Combination With PPARg Agonist Pioglitazone in Patients With Round Cell Myxoid Liposarcomas or Dedifferentiated G1 and G2 Liposarcomas With Stable Disease After a Monotherapy With Trabectedin. (TRABEPIO)

The primary activity endpoint is the number of responders. Patients will be considered as responders if they reach a CR or PR as best response during treatment according to RECIST criteria or according to Choi criteria.

The safety profile of T+P is assessed by the frequency and type of treatment emergent adverse events, graded according to NCI-CTCAE v5.0, frequency and nature of SAEs.

The analysis of \[Cmax\] will be performed on the first four enrolled patients within the safety analysis set 1.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Brightline-4: A Study to Test How Well Brigimadlin is Tolerated by People With a Type of Cancer Called Dedifferentiated Liposarcoma	NCT06058793	Liposarcoma, De...	Brigimadlin	18 Years -	Boehringer Ingelheim
Brightline-1: A Study to Compare Brigimadlin (BI 907828) With Doxorubicin in People With a Type of Cancer Called Dedifferentiated Liposarcoma	NCT05218499	Liposarcoma, De...	Brigimadlin (BI... Doxorubicin	18 Years -	Boehringer Ingelheim
Brightline-1: A Study to Compare Brigimadlin (BI 907828) With Doxorubicin in People With a Type of Cancer Called Dedifferentiated Liposarcoma	NCT05218499	Liposarcoma, De...	Brigimadlin (BI... Doxorubicin	18 Years -	Boehringer Ingelheim
Study on Trabectedin in Combination With Pioglitazone in Patients Myxoid Liposarcomas With Stable Disease After T Alone.	NCT04794127	Liposarcoma, My... Liposarcoma, De... Liposarcoma, Ro...	Trabectedin Pioglitazone Or...	18 Years -	Mario Negri Institute for Pharmacological Research

Spots Global Cancer Trial Database for liposarcoma, dedifferentiated