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.
Patients must have histologically or cytologically confirmed ER-positive and HER2- negative breast cancer as per the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines (Allison et al, 2020, Wolff et al, 2018).
Patients must have a confirmed ESR1 mutation. Note: This information will be drawn from patients' treatment charts. Mutational analysis will be done as standard of care; there is no research-related mutational testing for this study. ctDNA may be used for mutational testing.
Patients must have at least one measurable lesion (as per RECIST v1.1) lesion anywhere in the body or a mainly lytic metastatic bone lesion. Note: Lytic bone lesions with identifiable soft tissue components that can be evaluated by cross-sectional imaging techniques such as CT or MRI can be considered as measurable lesions if the soft tissue component meets the definition of measurability per RECIST v1.1.
Patients must have received at least 2 prior endocrine therapies, including a CDK4/6 inhibitor in the metastatic disease setting.
Patients who have received prior elacestrant.
Patients who have had chemotherapy or radiotherapy ≤ 28 days (6 weeks for nitrosureas or mitomycin C) prior to registration.
Patients who have taken steroid therapy or any other immunosuppressive therapy within 7 days of first dose prior to trial treatment.
Patients with brain metastases. Note: Patients with stable brain or subdural metastases are allowed if the patient has completed local therapy and was on a stable or decreasing dose of corticosteroids at baseline for brain management for at least 4 weeks before starting treatment in this study. The dose must be <2.0 mg/day of dexamethasone or equivalent. Any signs (e.g., radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment. RANO criteria are used to evaluate brain metastases
Single group
elacestrant, palbociclib, abemaciclib, ribociclib
DrugGiven orally
Progression-Free Survival (PFS)
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.
Adverse events
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.
Duration of Response (DOR)
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.
Overall Survival (OS)
Overall survival is calculated as the time that elapses between the day of patient registration and death from any cause, for all evaluable patients.
Click on the lead sponsor to view all of their trials.
Northwestern University
Lead sponsor
National Cancer Institute (NCI)
Collaborator
