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

NCT06062498 | Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: NU 23B05STU00219978NCI-2023-07168P30CA060553
• Study Type: interventional
• Target: 174
• Locations: 1 country
• Sites: 1

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.

Conditions

Estrogen-receptor-positive Breast Cancer; HER2/Neu-Negative Breast Cancer; Advanced Breast Cancerv; Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 5 years

Secondary Outcomes (3)

• Adverse events

  Up to 30 business days after end of treatment

• Duration of Response (DOR)

  Up to 5 years

• Overall Survival (OS)

  Up to 5 years

Study Arms (2)

Elacestrant Monotherapy

EXPERIMENTAL

Elacestrant (345 mg) will be taken orally once daily for each 28-day cycle. Courses repeat until progressive disease.

Drug: elacestrant, palbociclib, abemaciclib, ribociclib

Combination Therapy

EXPERIMENTAL

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

Drug: elacestrant, palbociclib, abemaciclib, ribociclib

Interventions

elacestrant, palbociclib, abemaciclib, ribociclib DRUG

Given orally

Combination Therapy; Elacestrant Monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• Note: In the context of this trial, ER status will be considered positive if \>10% of tumor cells demonstrate positive nuclear staining by immunohistochemistry. Note: Fresh biopsy is not a requirement.
• 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 must be age ≥ 18 years. Patients of childbearing potential (POCBP) may be premenopausal, postmenopausal, or perimenopausal.
• Potential POCBP who may be menopausal and are \< 55 years of age must have a serum follicle-stimulating hormone (FSH) level \> 40 mIU/mL to confirm menopause.
• Patients must exhibit an ECOG performance status of 0 or 1.
• Patients must have adequate organ and bone marrow function as defined below:
• Leukocytes (WBC) ≥ 3,000/mcL Absolute neutrophil count (ANC) ≥ 1,500/mcL Hemoglobin (Hgb) ≥ 80-100 g/dL Platelets (PLT) ≥ 50,000/mcL Total serum bilirubin \< 1.5 x Institutional upper limit of normal (ULN) AST (SGOT) ≤ 3 x institutional ULN (no liver metastases)
• x institutional ULN (liver metastases present) ALT (SGPT) ≤ 3 x institutional ULN
• x institutional ULN (liver metastases present) Cockcroft-Gault based creatinine clearance
• mL/min
• Note:
• Creatinine clearance (DMAB)

You may not qualify if:

• 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
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 3) with the exception of alopecia.
• Patients who are receiving any other investigational agents. For patients who were previously on palbociclib, abemaciclib, or ribociclib, the washout period between stopping that CDK4/6 inhibitor and starting a different one is 14 days.
• Patients with advanced, symptomatic visceral spread who are at risk of life-threatening complications in the short term, including massive uncontrolled effusions (peritoneal, pleural, pericardial), pulmonary lymphangitis, or liver involvement \>50%.
• Patients with documented pneumonitis/interstitial lung disease prior to registration.
• Patients who have received major surgery within 28 days before starting trial therapy.
• Patients who are taking strong or moderate CYP3A4 inducers or strong or moderate CYP3A4 inhibitors. See Section 4.4 for additional incompatibilities.
• Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following:
• Hypertension that is not controlled on medication
• Psychiatric illness/social situations that would limit compliance with study requirements
• Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints
• Patients with refractory or chronic nausea, gastrointestinal conditions (including significant gastric or bowel resection or gastric bypass surgery), history of malabsorption syndrome, or any other uncontrolled gastrointestinal condition that impact the absorption of the study drug. Similarly, patients who are unable to take/retain oral medications.

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

elacestrant; palbociclib; abemaciclib; ribociclib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• William Gradishar, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Coordinator

CONTACT

3126951301; cancer@northwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2023
• First Posted: October 2, 2023
• Study Start: September 29, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: October 20, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)