ELACESTRANT in Women and Men With CDK4/6 Inhibitor-Naive Estrogen Receptor Positive, HER-2 Negative Metastatic Breast Cancer Study

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the efficacy and safety of elacestrant over the course of 6 months in patients with ER+/HER2- advanced/metastatic breast cancer who received no prior CDK4/6i in the metastatic setting.

Detailed Description
-----------------
This is a Phase 2 trial evaluating the efficacy of elacestrant in patients with estrogen receptor positive (ER+)/human epidermal growth factor receptor-2 negative (HER2-) advanced/metastatic breast cancer who received one or two prior hormonal therapies and no prior cyclin-dependent kinase targeting enzymes CDK4 and CDK6 inhibitor (CDK4/6i) in the metastatic setting. The study duration for each patient is estimated to be: Screening Phase: Up to 21 days prior to Cycle 1, Day 1 (C1/D1); Treatment Phase: From C1/D1 until the date of radiologically documented progression, or treatment discontinuation due to other reasons. Survival Follow-Up Phase: All patients will be followed for survival approximately every 3 months up to 24 months after enrollment of the last patient. Patients will be followed for AEs for 28 days after the last treatment administration.

Official Title
-----------------
ELACESTRANT in Women and Men With CDK4/6 Inhibitor-Naive Estrogen Receptor Positive, HER-2 Negative Metastatic Breast Cancer: An Open-Label Multicenter Phase 2 Study (ELCIN)

Conditions
-----------------
Metastatic Breast Cancer

Intervention / Treatment
-----------------
* Drug: Elacestrant


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient has signed the informed consent before all study specific activities are conducted. Women or men aged ≥18 years (or the minimum age of consent as per local law), at the time of informed consent signature. Female patients may be either postmenopausal or premenopausal or perimenopausal. Premenopausal or perimenopausal women and men must be concurrently given a luteinizing hormone-releasing hormone (LHRH) agonist starting at least 4 weeks before the start of trial therapy and is planning to continue LHRH during the study. For perimenopausal women to be considered of non-childbearing potential, FSH levels must be >40 mIU/mL. Documentation of histopathologically or cytologically confirmed ER+, HER2-breast cancer, per local laboratory, 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. Patient has received at least one (and up to two) prior hormonal therapy in the advanced/metastatic setting. At least one measurable lesion as per RECIST version 1.1 or a mainly lytic bone lesion. 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 management of brain metastasis 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. ECOG performance status of 0 or 1. Patient has adequate bone marrow and organ function, as defined by the following laboratory values: Absolute neutrophil count (ANC) ≥1.5 × 109/L Platelets ≥100 × 109/L Hemoglobin ≥9.0 g/dL Potassium, sodium, calcium (corrected for serum albumin) and magnesium CTCAE grade ≤1 Cockcroft-Gault based creatinine clearance ≥50 mL/min. Note: Creatinine clearance (male) = ([140-age in years] × weight in kg)/ ([serum creatinine in mg/dL] × 72) Creatinine clearance (female) = (0.85 × [140-age in years] × weight in kg)/ ([serum creatinine in mg/dL] × 72) Serum albumin ≥3.0 g/dL (≥30 g/L) In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 × upper limit of normal (ULN). If the patient has liver metastases, ALT and AST ≤5 × ULN Total serum bilirubin <1.5 × ULN except for patients with Gilbert's syndrome who may be included if the total serum bilirubin is ≤3.0 × ULN or direct bilirubin ≤ 1.5 × ULN. Exclusion Criteria: Active or newly diagnosed central nervous system (CNS) metastases, including meningeal carcinomatosis. Patients with advanced, symptomatic visceral spread, that are at risk of life-threatening complications in the short term, including massive uncontrolled effusions (peritoneal, pleural, pericardial) and liver involvement of >50%. Prior chemotherapy, elacestrant, or CDK4/6i in the advanced/metastatic setting. Patient has a concurrent malignancy or history of invasive malignancy within 3 years of enrollment, with the exception of basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix that has completed curative therapy. Uncontrolled significant active infections. Patients with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection must have undetectable viral load during screening. Patients known to be HIV+ are allowed as long as they have undetectable viral load at baseline. Major surgery or radiotherapy within 28 days before starting trial therapy. Inability to take oral medication, refractory or chronic nausea, gastrointestinal condition (including significant gastric or bowel resection), history of malabsorption syndrome, or any other uncontrolled gastrointestinal condition that may impact the absorption of study drug. Known intolerance to elacestrant or any of its excipients. Females of childbearing potential who within 28 days before starting trial therapy, did not use a highly effective method of contraception. Females of childbearing potential who do not agree to use a highly effective method of contraception throughout the entire study period and for 28 days after trial therapy discontinuation. Note: Please refer to Recommendations related to contraception and pregnancy testing in clinical trials for additional details. Men who do not agree to abstain from donating sperm, or to use a highly effective method of contraception, during the course of the treatment period and for 120 days thereafter. Patient is currently receiving or received any of the following medications prior to first dose of trial therapy: Investigational anti-cancer therapy within 14 days (28 days in case of anticancer antibody-based treatments) or 5 half-lives, whichever is shorter. Fulvestrant treatment (last injection) <42 days before first dose of study drug. Any other endocrine therapy <14 days before first dose of study drug. Known strong or moderate inducers or inhibitors of cytochrome P450 (CYP) 3A4 within 14 days or 5 half-lives, whichever is shorter. Herbal preparations/medications within 7 days. These include, but are not limited to, St. John's wort, kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng. Evidence of ongoing alcohol or drug abuse as assessed by the investigator.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Elacestrant<br>Subjects will take a starting dose of 400 mg of elacestrant dihydrochloride in tablet form once daily for up to 6 months. | Drug: Elacestrant<br>* Starting dose 400 mg elacestrant dihydrochloride administered orally once daily for an estimated 6 months of treatment.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival rate | Rate is defined as percentage of subjects achieving progression-free survival, defined as time from the date of the first dose to the date of the first radiological documentation of disease progression or death, whichever comes first. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | Proportion of patients who achieve a best overall response of partial response or complete response | 24 months | 
| Duration of response | Time from the date of first documented complete response or partial response until the first radiological documentation of disease progression or death, whichever comes first | 36 months | 
| Clinical benefit rate | Proportion of patients who achieve a best overall response of confirmed complete response or partial response or durable stable disease (duration at least 24 weeks from date of first dose) | 36 months | 
| Overall survival | Time from the date of the first dose to the date of the first radiological documentation of disease progression or death, whichever comes first | 36 months | 
| Progression-free survival | Time from the date of the first dose to the date of the first radiological documentation of disease progression or death, whichever comes first | 36 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
metastatic breast cancer, breast cancer, elacestrant