Elacestrant vs Elacestrant Plus a CDK4/6 Inhibitor in Patients With ERpositive/HER2-negative Advanced or Metastatic Breast Cancer

Phase 2

Not yet recruiting

• Conditions: Metastatic Breast Cancer; Advanced Breast Cancerv; Estrogen-receptor-positive Breast Cancer; HER2/Neu-Negative Breast Cancer
• Interventions: Drug: elacestrant, palbociclib, abemaciclib, ribociclib

• Registration Number: NCT06062498
• Lead Sponsor: Northwestern University

Brief Summary

Breast cancer is not only the leading cause of cancer in women, but also the leading cause of cancer deaths in women. Estrogen receptor-positive and HER2-negative breast cancer is the most prevalent breast cancer subtype. Endocrine therapy is the mainstay of treatment; however, due to the varied nature of the disease, development of resistance to this therapeutic approach is very common in the metastatic setting.

The purpose of this study is to see whether the effectiveness of elacestrant can be enhanced by combining it with a targeted agent such as a CDK4/6 inhibitor to treat patients with ER+/HER2- or metastatic breast cancer with prior exposure to a CDK4/6 inhibitor.

Detailed Description

Primary Objective I. Evaluate progression-free survival (PFS) of patients with advanced or metastatic ERpositive/HER2-negative breast cancer who have been treated with either elacestrant monotherapy or combination therapy of elacestrant with a CDK4/6 inhibitor (palbociclib, abemaciclib, or ribociclib). PFS of the elacestrant monotherapy arm will be compared with PFS of the combination therapy arm.

Secondary Objectives I. Assess toxicity profile of elacestrant combination therapy with a CDK4/6 inhibitor (palbociclib, abemaciclib, or ribociclib) in advanced or metastatic ER-positive/HER2- negative breast cancer according to NCI-CTCAE v5.0.

II. Assess duration of response (DOR) in patients with advanced or metastatic ERpositive/HER2-negative breast cancer who have been treated with either elacestrant monotherapy or combination therapy of elacestrant with a CDK4/6 inhibitor (palbociclib, abemaciclib, or ribociclib). DOR of the elacestrant monotherapy arm will be compared with DOR of the combination therapy arm. III. Determine overall survival (OS) in patients with advanced or metastatic ER-positive, HER2-negative breast cancer who have been treated with either elacestrant monotherapy or combination therapy of elacestrant with a CDK4/6 inhibitor (palbociclib, abemaciclib, or ribociclib). OS of the elacestrant monotherapy arm will be compared with OS of the combination therapy arm.

OUTLINE:

Patients will receive either elacestrant monotherapy or combination therapy with a CDK4/6 inhibitor (palbociclib, abemaciclib, or ribociclib) orally for each 28 day cycle until progressive disease, unacceptable toxicity, treating physician decision, or patient withdrawal of consent.

Patients will be followed (either by routine clinic visit or by phone call) every 36 weeks for 2 years and then every 72 weeks up to 5 years total from time of registration to document survival and disease progression.

Study Timeline

• Status Verified: 2023-09
• Study First Submitted: 2023-09-25
• Study First Submitted QC: 2023-09-25
• Last Update Submitted: 2023-09-25
• Study Start: 2023-09-30
• Study First Posted: 2023-10-02
• Last Update Posted: 2023-10-02
• Primary Completion: 2024-07-01
• Study Completion: 2025-07-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 174

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Elacestrant Monotherapy	elacestrant, palbociclib, abemaciclib, ribociclib	Elacestrant (345 mg) will be taken orally once daily for each 28-day cycle. Courses repeat until progressive disease.
Combination Therapy	elacestrant, palbociclib, abemaciclib, ribociclib	Patients will receive either: Elacestrant 345 mg orally once daily + Palbociclib 125 mg orally once daily for 21 days out of 28-day cycle OR Abemaciclib 150 mg orally twice daily OR Ribociclib 600 mg orally once daily for 21 days out of 28-day cycle

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS)	Up to 5 years	The primary endpoint of PFS for elacestrant or combination therapy (elacestrant and either palbociclib, abemaciclib, or ribociclib) will involve calculation of the progression-free survival time as the time that elapses between time of treatment initiation and first documented disease progression or death from any cause (whichever comes first). For PFS analysis, disease progression is defined as progressive disease (PD) per RECIST v1.1. The PFS results from the two treatment arms will be compared.

Secondary Outcome Measures

Name	Time	Method
Duration of Response (DOR)	Up to 5 years	For DOR analysis, response is defined as confirmed complete response (CR) or confirmed partial response (PR) per RECIST v1.1. Disease progression is defined as progressive disease (PD) per RECIST v1.1.
Adverse events	Up to 30 business days after end of treatment	To determine toxicity, grading will be evaluated using NCI CTCAE v5.0. Adverse events will be assessed from start of therapy up to 30 business days after treatment discontinuation.
Overall Survival (OS)	Up to 5 years	Overall survival is calculated as the time that elapses between the day of patient registration and death from any cause, for all evaluable patients.

Trial Locations

Locations (1)

Northwestern University; 🇺🇸 Chicago, Illinois, United States