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

Metastatic Breast Cancer Clinical Trial

— ELCIN  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05596409
• Other study ID #: STML-ELA-0322
• Status: Recruiting
• Phase: Phase 2
• Start date: May 19, 2023
• Est. completion date: August 2025

Study information

• Verified date: April 2024
• Source: Stemline Therapeutics, Inc.
• Contact: Stemline Trials
• Phone: 877-332-7961
• Email: clinicaltrials[@]menarinistemline.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: August 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patient has signed the informed consent before all study specific activities are conducted.

2. 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.

1. 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.

2. For perimenopausal women to be considered of non-childbearing potential, FSH levels must be >40 mIU/mL.

3. 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.

4. Patient has received at least one (and up to two) prior hormonal therapy in the advanced/metastatic setting.

5. 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.

6. ECOG performance status of 0 or 1.

7. Patient has adequate bone marrow and organ function, as defined by the following laboratory values:

1. Absolute neutrophil count (ANC) =1.5 × 109/L

2. Platelets =100 × 109/L

3. Hemoglobin =9.0 g/dL

4. Potassium, sodium, calcium (corrected for serum albumin) and magnesium CTCAE grade =1

5. 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)

6. Serum albumin =3.0 g/dL (=30 g/L)

7. 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

8. 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:

1. Active or newly diagnosed central nervous system (CNS) metastases, including meningeal carcinomatosis.

2. 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%.

3. Prior chemotherapy, elacestrant, or CDK4/6i in the advanced/metastatic setting.

4. 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.

5. Uncontrolled significant active infections.

6. Patients with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection must have undetectable viral load during screening.

7. Patients known to be HIV+ are allowed as long as they have undetectable viral load at baseline.

8. Major surgery or radiotherapy within 28 days before starting trial therapy.

9. 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.

10. Known intolerance to elacestrant or any of its excipients.

11. Females of childbearing potential who within 28 days before starting trial therapy, did not use a highly effective method of contraception.

12. 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.

13. 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.

14. Patient is currently receiving or received any of the following medications prior to first dose of trial therapy:

1. Investigational anti-cancer therapy within 14 days (28 days in case of anticancer antibody-based treatments) or 5 half-lives, whichever is shorter.

2. Fulvestrant treatment (last injection) <42 days before first dose of study drug.

3. Any other endocrine therapy <14 days before first dose of study drug.

4. Known strong or moderate inducers or inhibitors of cytochrome P450 (CYP) 3A4 within 14 days or 5 half-lives, whichever is shorter.

5. 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.

15. Evidence of ongoing alcohol or drug abuse as assessed by the investigator.

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Elacestrant
Starting dose 400 mg elacestrant dihydrochloride administered orally once daily for an estimated 6 months of treatment.

Locations

Country	Name	City	State
Brazil	Hospital de Amor de Barretos	Barretos	São Paulo
Brazil	Centro de Pesquisas Oncologicas	Florianópolis	Santa Catarina
Brazil	Hospital São Lucas PUCRS - Centro de Pesquisa em Oncologia (CPO)	Porto Alegre	Rio Granda Do Sul
Brazil	Centro de Estudos e Pesquisas de Hematologia e Oncologia- CEPHO	Santo Andre	São Paulo
Brazil	Clinica de Pesquisas e Centro de Estudos Em Oncologia Ginecologica e Mamaria Ltda	São Paulo
Bulgaria	COMPLEX ONCOLOGICAL CENTER - Shumen	Shumen
Bulgaria	COC Veliko Tarnovo	Veliko Tarnovo
Georgia	Cancer Research Centre	Tbilisi
Georgia	Innova Medical Center	Tbilisi
Georgia	Institute of Clinical Oncology	Tbilisi
Georgia	LTD Simon Khechinashvili University Clinic	Tbilisi
Georgia	Multiprofile Clinic Consilium Medulla	Tbilisi
Georgia	Todua Clinic	Tbilisi
Romania	Institutul Oncologic "Prof. Dr. Ion Chiricuta" Cluj Napoca	Cluj Napoca	Cluj
Romania	Centrul de Oncologie "Sf. Nectarie"	Craiova	Dolj
United States	OPN Healthcare	Arcadia	California
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	Morton Plant Hospital - Baycare Health System	Clearwater	Florida
United States	Inventa Center for Cancer Research at Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Alliance for Multispecialty Research	Merriam	Kansas
United States	UT Health San Antonio Mays Cancer Center	San Antonio	Texas
United States	Highlands Oncology Group, PA	Springdale	Arkansas
United States	Quality Cancer Care Alliance (QCCA) Northwest Medical Specialties	Tacoma	Washington
United States	The Toledo Clinic	Toledo	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Stemline Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Brazil,  Bulgaria,  Georgia,  Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall response rate	Proportion of patients who achieve a best overall response of partial response or complete response	24 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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