NCT05932667

Milademetan and Fulvestrant in GATA3-mutant, ER+HER- Advanced or Metastatic Breast Cancer

Milademetan and Fulvestrant in GATA3-mutant, ER-positive, HER2-negative Advanced or Metastatic Breast Cancer Patients: a Multicenter Phase II Trial

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 1 (actual)
• Sponsor: Institut Curie · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a single arm, multicentric phase II study of milademetan plus fulvestrant in patients with ER+, HER2- ABC harboring GATA3 mutation(s) in the tumor and/or in ctDNA who have progressed on or after prior treatments including a CDK4/6 inhibitor. Frameshift or truncating GATA3 mutations will be identified by next generation sequencing (NGS) performed on either tissue or circulating DNA. Given the well-known safety profile of fulvestrant and the absence of significant toxicity expected from the association of fulvestrant and milademetan, a safety run-in is planned. During the course of the study, the Steering Committee will specifically review the occurrence of toxicities defined as DLTs in the safety run-in.

Detailed description

This is a single arm, multicentric phase II study designed to evaluate the efficacy and safety of milademetan-fulvestrant combination in patients with ER+ advanced breast cancer. The trial is dedicated to patients experiencing disease progression after one prior line of endocrine therapy, including a prior CDK4/6 inhibitor, but no more than 2 prior lines of endocrine therapy for metastatic disease. No more than 2 prior lines of chemotherapy for metastatic disease is allowed. The study selection step includes the confirmation of GATA3 mutational status, either with a result already available, or following informed consent form signature, and mutationnal and analysis of FFPE block available as per inclusion criteria. The study treatment step is divided into two successive parts: a safety run-in part followed by a phase II part. In the safety run-in, 6 patients will be included at dose D (milademetan 260mg qdx3 every 14 days twice in a 28-day cycle and fulvestrant 500mg IM at Day1, Day15 of cycle 1, then Day1 of every 28 day-cycle. In case of unacceptable toxicity at the D-dose, a D-1 dose will be investigated, followed by a D-2 dose in case of unacceptable toxicity at D-1 dose. In the phase II, patients will be treated at the milademetan dose recommended in the safety run-in. Dose reductions will be allowed on subsequent cycles in case of toxicity. Patients will continue to receive study drug treatment until progression of disease, unacceptable toxicity, patient withdrawal of consent, Investigator decision, lost to follow-up, death, patient non-compliance, or study termination by Sponsor.

Conditions

• Advanced or Metastatic Breast Cancer

Interventions

Type	Name	Description
DRUG	Milademetan	The study treatment, including a combination of milademetan and fulvestrant, is administered into two successive parts: a safety run-in part followed by a phase II part. Once GATA3 mutational status confirmed, patients will continue to receive study drug treatment until progression of disease, unacceptable toxicity, patient withdrawal of consent, Investigator decision, lost to follow-up, death, patient non-compliance, or study termination by Sponsor.
BEHAVIORAL	Patient Reported Outcomes (PROs) and Health-Related Quality of Life (HRQOL)	Measure of interest is the mean difference in the change from baseline to different specific visit (each disease radiological assessment, disease progression and/or treatment discontinuation) in total/subscale scores of the 5 Dimension 5 Level (EQ-5D-5L) scale and the EORTC-QLQ-C30 questionnaire

Timeline

• Start date: 2023-10-12
• Primary completion: 2023-11-24
• Completion: 2023-11-30
• First posted: 2023-07-06
• Last updated: 2023-12-21

Locations

6 sites across 1 country: France