This phase II trial compares the effect of elacestrant alone to elacestrant plus a CDK4/6 inhibitor (palbociclib, abemaciclib, or ribociclib) in patients with an ESR1 mutation and estrogen receptor (ER)-positive and HER2-negative breast cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or has spread from where it first started (primary site) to other places in the body (metastatic). Breast cancer is not only the leading cause of cancer in women, but also the leading cause of cancer deaths in women. ER-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 disease that does not respond to endocrine treatment (resistance) is very common in the metastatic setting. There remains an unmet need for more effective therapies for patients with ER-positive/HER2-negative, metastatic breast cancer. Partnering targeted therapy with endocrine agents have proven more effective than therapy with an endocrine agent alone, particularly after disease progression. Elacestrant is a selective estrogen receptor degrader (SERD), a type of antiestrogen therapy. SERDs fill estrogen receptors to stop this hormone from attaching to tumor cells and helping them grow. These medicines also reduce the number of estrogen receptors and change the receptors that remain so they don't work as well. CDK4/6 inhibitors, such as palbociclib, abemaciclib, or ribociclib, is a type of targeted therapy that may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Information gained from this study may allow researchers to determine if the effectiveness of elacestrant can be enhanced by combining it with CDK4/6 inhibitor to treat patients with an ESR1 mutation and ER-positive/HER2-negative, advanced or metastatic breast cancer.
Additional locations may be listed on ClinicalTrials.gov for NCT06062498.
Locations matching your search criteria
United States
Illinois
Chicago
Northwestern UniversityStatus: Active
Contact: William John Gradishar
Phone: 312-695-0990
PRIMARY OBJECTIVE:
I. Evaluate progression-free survival (PFS) of patients with advanced or metastatic estrogen receptor (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). 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 National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.
II. Assess duration of response (DOR) 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). 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 are randomized to 1 of 2 arms.
ARM I: Patients receive elacestrant orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a bone scan during screening and on trial as clinically indicated as well as computed tomography (CT) or magnetic resonance imaging (MRI) throughout the trial.
ARM II: Patients receive elacestrant PO QD on days 1-28 of each cycle and a CDK4/6 inhibitor with either palbociclib PO QD on days 1-21 of each cycle, abemaciclib PO twice daily (BID) on days 1-28 of each cycle, or ribociclib PO QD on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a bone scan during screening and on trial as clinically indicated as well as CT or MRI throughout the trial.
Upon completion of study treatment, patients are followed up within 30 days and every 36 weeks for 2 years and then every 72 weeks for up to 5 years total from time of registration.
Lead OrganizationNorthwestern University
Principal InvestigatorWilliam John Gradishar
