Brightline-4: A study to test how well brigimadlin is tolerated by people with a type of cancer called dedifferentiated liposarcoma

JRCT ID: jRCT2071230107

Registered date:18/01/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Dedifferentiated liposarcoma
• Date of first enrollment: 01/03/2024
• Target sample size: 37
• Countries of recruitment: US,Japan,Argentina,Japan,Australia,Japan,Belguim,Japan,Brazil,Japan,Canada,Japan,Italy,Japan,UK,Japan
• Study type: Interventional
• Intervention(s): Oral, single 45 mg dose, on Day 1 q3w

Outcome(s)

Primary Outcome

- Occurrence of TEAEs according to Common Terminology Criteria for Adverse Events (CTCAE) version 5 during the entire treatment period
- Occurrence of TEAEs with Grade >=3 according to CTCAE version 5 during the entire treatment period

Secondary Outcome

- Occurrence of treatment-emergent serious adverse events (SAEs)
- Occurrence of TEAEs leading to study treatment discontinuation
- Occurrence of TEAEs leading to dose reduction
- Occurrence of TEAEs leading to dose delay
- Occurrence of TEAEs of special interest
- Objective response
- Progression-free survival
- Overall survival
- Duration of objective response
- Disease control

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Male or female patients >=18 years old at the time of signature of the informed consent form
- Women of childbearing potential and men able to father a child must be ready and able to use two medically acceptable methods of birth control that result in a low failure rate of <1% per year when used consistently and correctly beginning at screening, during study participation, and until 6 months and 12 days after last dose for women and 102 days after last dose for men
- Histologically documented locally advanced or metastatic, unresectable, progressive or recurrent DDLPS, meeting the criteria for an open study cohort:
* Cohort A: patient has not received prior systemic therapy for DDLPS in any setting (including adjuvant, neoadjuvant, maintenance, palliative)
* Cohort B: patient has received any prior systemic therapy for DDLPS in any setting (including adjuvant, neoadjuvant, maintenance, palliative)
- Written pathology report indicating the diagnosis of DDLPS with positive MDM2 immunohistochemistry or MDM2 amplification as demonstrated by fluorescence in situ hybridisation or next-generation sequencing
- Presence of at least 1 measurable target lesion according to RECIST version 1.1
- Eastern Cooperative Oncology Group performance status of 0 or 1
- Life expectancy >=3 months at the start of treatment in the opinion of the investigator
- All toxicities related to previous anticancer therapies have resolved to CTCAE Grade <=1 prior to study treatment administration (except for alopecia and amenorrhoea or menstrual disorders which can be any grade, and peripheral neuropathy which must be of CTCAE Grade <=2)
- Adequate organ function

Exclude criteria

- Known mutation in the TP53 gene
- Major surgery performed within 4 weeks prior to start of study treatment or planned within 6 months after screening
- Previous administration of brigimadlin or any other MDM2-p53 or MDM4 regulator of p53 (MDM4, MDMX)-p53 antagonist
- Previous treatment in study 1403-0008 (Brightline-1)
- Having to receive, or intending to receive, restricted medications or any drug considered likely to interfere with the safe conduct of the study
- Receiving treatment for brain metastases or leptomeningeal disease which may interfere with safety and/or endpoint assessment
- Unable to swallow the study treatment
- Previous or concomitant malignancies other than the one treated in this study within the previous 2 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
- Any history or presence of uncontrolled GI disorders that could affect the intake and/or absorption of the study treatment in the opinion of the investigator
- History or presence of clinically relevant cardiovascular abnormalities
- Active bleeding, significant risk of haemorrhage, or current bleeding disorder
- Any history of or concomitant condition that, in the opinion of the investigator, would compromise the patients ability to comply with the study or interfere with the evaluation of the safety and efficacy of the study treatment
- Patients not expected to comply with the protocol requirements or not expected to complete the study as scheduled
- Active major infection requiring systemic treatment at treatment start in this study

Related Information

• Primary Sponsor: Hagimori Kenta
• Secondary ID(s): NCT06058793