Open-Label Umbrella Study To Evaluate Safety And Efficacy Of Elacestrant In Various Combination In Participants With Metastatic Breast Cancer

NCT05563220 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STML-ELA-0222
• Study Type: interventional
• Target: 435
• Locations: 13 countries
• Sites: 83

Brief Summary

This is a multicenter, Phase 1b/2 trial in participants with estrogen receptor positive/human epidermal growth factor receptor 2 negative (ER+/HER2-) advanced/metastatic breast cancer. The phase 1b part of the trial will determine the recommended Phase 2 dose (RP2D) of elacestrant when administered in combination with alpelisib, everolimus, palbociclib, capivasertib, and ribociclib. The Phase 2 part of the trial will evaluate the efficacy and safety of the various combinations.

Conditions

Metastatic Breast Cancer; Breast Cancer

Keywords

breast cancer

Outcome Measures

Primary Outcomes (2)

• Number of Participants with DLTs Observed During the First Cycle

  Number of dose-limiting toxicities during the first cycle

  28 days

• Progression-free Survival

  The 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 Outcomes (6)

• Standard Pharmacokinetics (PK) Parameters Including AUC0-tau, Cmax, Tmax, and Ctrough

  36 months

• Overall Response Rate

  36 months

• Duration of Response

  36 months

• Clinical Benefit Rate

  36 months

• Progression-free Survival Rate

  36 months

Study Arms (5)

Phase 1b Arm A: elacestrant with alpelisib

EXPERIMENTAL

Elacestrant Dihydrochloride 300 milligrams (mg) or 400 mg + Alpelisib 150 mg to 250 mg

Drug: Elacestrant; Drug: Alpelisib

Phase 1b Arm B: elacestrant with everolimus

EXPERIMENTAL

Elacestrant Dihydrochloride 300 mg or 400 mg + Everolimus 5.0 mg, 7.5 mg or possibly 10 mg

Drug: Elacestrant; Drug: Everolimus

Phase 1b Arm C: elacestrant with abemaciclib or ribociclib:

EXPERIMENTAL

Elacestrant Dihydrochloride 100 mg, 200 mg, 300 mg + Ribociclib 400 mg or possibly 600 mg The RP2D for the combination of elacestrant and abemaciclib is evaluated in the ongoing ELECTRA trial (ClinicalTrials.gov Identifier: NCT04791384)

Drug: Elacestrant; Drug: Ribociclib; Drug: Abemaciclib

Phase 1b Arm D: elacestrant with either palbociclib, abemaciclib, or ribociclib (no prior CDK4/6i)

EXPERIMENTAL

Elacestrant Dihydrochloride 300 mg or 400 mg + Palbociclib 100 mg,125 mg or the RP2D for the combination of elacestrant and abemaciclib is evaluated in the ongoing ELECTRA trial (ClinicalTrials.gov Identifier: NCT04791384) Elacestrant 86 mg, 172 mg, 258 mg + Ribociclib 400 mg or possibly 600 mg

Drug: Elacestrant; Drug: Ribociclib; Drug: Palbociclib; Drug: Abemaciclib

Phase 1b Arm E:

EXPERIMENTAL

Elacestrant Dihydrochloride 300 mg, 400 mg + Capivasertib 200 mg, 320 mg, 400 mg

Drug: Elacestrant; Drug: Capivasertib

Interventions

Alpelisib DRUG

Alpelisib 150 mg or 250 mg once daily in cycles of 28 days

Also known as: Piqray

Phase 1b Arm A: elacestrant with alpelisib

Everolimus DRUG

Everolimus 5 mg, 7.5 mg, or 10 mg once daily in cycles of 28 days

Also known as: Afinitor

Phase 1b Arm B: elacestrant with everolimus

Ribociclib DRUG

Ribociclib 400 mg or 600 mg once daily for 21 days followed by 7 days off in cycles of 28 days

Also known as: Kisqali

Phase 1b Arm C: elacestrant with abemaciclib or ribociclib:; Phase 1b Arm D: elacestrant with either palbociclib, abemaciclib, or ribociclib (no prior CDK4/6i)

Elacestrant DRUG

Elacestrant 86 mg, 172 mg, 258 mg or 345 mg once daily in cycles of 28 days

Phase 1b Arm A: elacestrant with alpelisib; Phase 1b Arm B: elacestrant with everolimus; Phase 1b Arm C: elacestrant with abemaciclib or ribociclib:; Phase 1b Arm D: elacestrant with either palbociclib, abemaciclib, or ribociclib (no prior CDK4/6i); Phase 1b Arm E:

Palbociclib DRUG

Palbociclib 100 mg or 125 mg once daily for 21 days followed by 7 days off in cycles of 28 days

Also known as: Ibrance

Phase 1b Arm D: elacestrant with either palbociclib, abemaciclib, or ribociclib (no prior CDK4/6i)

Capivasertib DRUG

Capivasertib 200 mg or 320 mg or 400 mg twice daily for 4 days on, 3 days off in cycles of 28 days

Also known as: Truqap

Phase 1b Arm E:

Abemaciclib DRUG

Abemaciclib 100 mg or 150 mg twice daily in cycles of 28 consecutive days

Also known as: Verzenio

Phase 1b Arm C: elacestrant with abemaciclib or ribociclib:; Phase 1b Arm D: elacestrant with either palbociclib, abemaciclib, or ribociclib (no prior CDK4/6i)

Eligibility Criteria

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

You may qualify if:

• Participant has signed the informed consent before all study specific activities are conducted.
• Women or men aged ≥18 years (or the minimum age of consent in accordance with the local law), at the time of informed consent signature. Female participants may be of any menopausal status.
• Postmenopausal status is defined as follows or in accordance with local regulations:
• Age ≥60 years or
• Age \<60 years and amenorrhea for 12 or more months (without an alternative cause) and follicle-stimulating hormone value and an estradiol level within the postmenopausal range per local laboratory reference or
• Documentation of bilateral oophorectomy, at least 1 month before first dose of trial therapy.
• Premenopausal and perimenopausal women (who do not fit postmenopausal criteria) and men must be receiving a luteinizing hormone-releasing hormone (LHRH) agonist and must be initiated at least 3 weeks (4 depending on local label) before the start of trial therapy and are planning to continue LHRH agonist treatment during the study treatment.
• Histopathological or cytological confirmed ER+, HER2-, breast cancer, per local laboratory, as per the American Society of Clinical Oncology/College of American Pathologists guidelines. Note: In the context of this trial, ER status will be considered positive if ≥10% of tumor cells demonstrate positive nuclear staining by immunohistochemistry, with or without progesterone positivity.
• Documented radiological disease progression during or after the most recent therapy.
• At least 1 measurable lesion as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Tumor lesions previously irradiated or subjected to any locoregional treatment will only be considered measurable if there is clear, documented progression at the treated site. For participants with bone only disease, lesions: must be lytic or mixed (lytic + blastic / sclerotic), confirmed and accurately assessed by computed tomography or magnetic resonance imaging, and must have an identifiable soft tissue component meeting the definition of measurability per RECIST v1.1. Note: participants with blastic / sclerotic bone lesions only are not eligible.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• Participant has adequate bone marrow and organ function, as defined by the following laboratory values:
• Absolute neutrophil count ≥1.5 × 10\^9/liter (L)
• Platelets ≥100 × 10\^9/L
• Hemoglobin ≥9.0 grams/deciliter (g/dL)

You may not qualify if:

• Active or newly diagnosed central nervous system metastases, or meningeal carcinomatosis. Note: Participants with stable brain or subdural metastases are allowed if the participant 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 (for example, radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment.
• Participants 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%.
• Prior chemotherapy or elacestrant in the advanced/metastatic setting.
• Participants with known germline BRCA mutation without prior treatment with a PARP inhibitor before study entry.
• Participant has a concurrent malignancy or history of invasive malignancy within 3 years of enrollment, except basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix that has completed curative therapy. Other malignancies with low risk of recurrence may be considered eligible with Sponsor approval.
• Uncontrolled significant active infections.
• Participants with hepatitis B virus and/or hepatitis C virus infection must have undetectable viral load during screening.
• Participants known to be human immunodeficiency virus+ are allowed if they have undetectable viral load at baseline.
• Documented pneumonitis/interstitial lung disease prior to Cycle 1 Day 1.
• Major surgery within 28 days before starting trial therapy.
• Inability to take oral medications, refractory or chronic nausea, gastrointestinal conditions (including significant gastric or bowel resection), history of malabsorption syndrome, or any other uncontrolled gastrointestinal condition that impact the absorption of the study drug.
• Known intolerance to elacestrant or any of its excipients.
• Pregnant and breast-feeding women are excluded from the study. In addition, women of childbearing potential are excluded who:
• Within 28 days before starting trial therapy, did not use a highly effective method of contraception.
• Do not agree to use a highly effective method of contraception (Appendix F) or abstain from heterosexual intercourse throughout the entire study period and for 120 days after trial therapy discontinuation.

Sponsors & Collaborators

• Stemline Therapeutics, Inc.: lead

Study Sites (83)

Dothan Hematology and Oncology

Dothan, Alabama, 36303, United States

Location

Mayo Clinic - Arizona

Phoenix, Arizona, 85054, United States

Location

Highlands Oncology Group

Springdale, Arkansas, 72762, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

OPN Healthcare (Los Alamitos Location)

Los Alamitos, California, 90720, United States

Location

Cedars Sinai

Los Angeles, California, 90048, United States

Location

UCLA UCLA Hem/Onc - Clinical Research Unit

Los Angeles, California, 90095, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158, United States

Location

TOI Clinical Research

Whittier, California, 90603, United States

Location

Rocky Mountain Cancer Centers

Lone Tree, Colorado, 80124, United States

Location

George Washington Cancer Center

Washington D.C., District of Columbia, 20037, United States

Location

Advent Health (Florida Hospital) - Altamonte Springs

Altamonte Springs, Florida, 32701, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Northwestern Feinberg Scholl of Medicine Prentice Women's Hospital

Chicago, Illinois, 60611, United States

Location

MD Alliance for Multispecialty Research, LLC

Merriam, Kansas, 66204, United States

Location

Johns Hopkins School of Medicine

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine in St. Louis

St Louis, Missouri, 63110, United States

Location

Astera Cancer Care

East Brunswick, New Jersey, 08816, United States

Location

Summit Medical Group

Florham Park, New Jersey, 07932, United States

Location

Cooperman Barnabas Medical Center

New Brunswick, New Jersey, 08901, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

W&IH of RI Breast Health Center of Women and Infants Hospital of Rhode Island

Providence, Rhode Island, 02905, United States

Location

Sarah Cannon Research Institute / Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

MD Anderson Cancer Center Texas

Houston, Texas, 77030, United States

Location

UT Health San Antonio

San Antonio, Texas, 78229, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

Cancer Care Northwest

Spokane Valley, Washington, 99216, United States

Location

Northwest Medical Specialties (Nwms) - Puyallup - Medical Oncology (Rainier Hematology-Oncology)/Exigent Research Network; LLC

Tacoma, Washington, 98405, United States

Location

University of WI - Carbone Cancer Center (Phase II only)

Madison, Wisconsin, 53792, United States

Location

Centro Medico Austral

Buenos Aires, C1017AAS, Argentina

Location

Cemaic - Centro De Especialidades Medicas Ambulatorias E Investigacion Clinica

Córdoba, X5008HHW, Argentina

Location

Centro Oncologico Riojano Integral (Cori)

La Rioja, 01122, Argentina

Location

Macquarie University

Sydney, 2113, Australia

Location

Institut Jules Bordet

Anderlecht, 01070, Belgium

Location

Grand Hôpital de Charleroi - Site Notre Dame

Charleroi, 06000, Belgium

Location

Universitaire Ziekenhuizen (Uz) Leuven - Campus Gasthuisberg - Multidisciplinair Borstcentrum (Multidisciplinary Breast Center) (Mbc)

Leuven, 03000, Belgium

Location

ACCG - Hospital Araujo Jorge

Goiânia, 74605-070, Brazil

Location

Clinica Neoplasias Litoral

Itajaí, 88301-220, Brazil

Location

Hospital Sao Lucas da PUCRS

Porto Alegre, 90610-000, Brazil

Location

Centro Gaucho Integrado de Oncologia; Hematologia; Ensino e Pesquisa - Hospital Mae de Deus/AESC

Porto Alegre, 90850-170, Brazil

Location

Hospital Sirio-Libanes (HSL) - Centro De Oncologia - Sao Paulo

São Paulo, 01308-050, Brazil

Location

Centre Hospitalier Lyon SUD- HCL

Lyon, 69495, France

Location

Centre de Cancérologie du Grand Montpellier

Montpellier, 34070, France

Location

Centre de Cancérologie du Grand Montpellier

Rouen, 76038 Cedex 1, France

Location

Centre Hospitalier Universitaire (Chu) De Toulouse - Institut Universitaire Du Cancer De Toulouse-Oncopole (Iuct-Oncopole) (Institut Claudius Regaud)

Toulouse, 31059 Cedex 09, France

Location

Institut Gustave-Roussy-Umr 981

Villejuif, 94805, France

Location

Samson Assuta Ashdod University Hospital - The Institute of Oncology

Ashdod, 7747629, Israel

Location

Rambam Heath

Haifa, 352408, Israel

Location

Shaare Zedek Medical Center

Jerusalem, 9103102, Israel

Location

Davidoff Rabin Medical Center

Petah Tikva, 49100, Israel

Location

Sheba Medical Center; Center Israel

Ramat Gan, 5265601, Israel

Location

ASST degli Spedali Civili di Brescia

Brescia, 25123, Italy

Location

Istituto Europeo di Oncologia (IEO)

Milan, 20141, Italy

Location

Istituto Nazionale Tumori "Fondazione PASCALE"

Naples, 80131, Italy

Location

Ospedale Infermi di Rimini - Azienda Unita Sanitaria Locale Della Romagna

Rimini, 47923, Italy

Location

Centre Hospitalier De L'Ardenne

Libramont, 06800, Luxembourg

Location

Seoul National University Bundang Hospital

Seongnam-si, 13620, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Gangnam Severance Hospital

Seoul, 06273, South Korea

Location

Complejo Hospitalario Universitario A Coruna

A Coruña, 15006, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic Barcelona

Barcelona, 08036, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

IOB Madrd Institute of Oncology Hospital Beata Maria Ana de Jesus

Madrid, 28007, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

NEXT Madrid

Pozuelo de Alarcón, 28223, Spain

Location

Fundacion Instituto Valeciano De Oncologia

Valencia, 46009, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital Arnau De Vilanova

Valencia, 46015, Spain

Location

Abdurrahman Yurtaslan Oncology Hospital

Ankara, 0*6200, Turkey (Türkiye)

Location

The Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, L7 8YA, United Kingdom

Location

North Middlesex University Hospital

London, N18 1QX, United Kingdom

Location

Sarah Cannon Research Institute UK; Ltd

London, W1G 6AD, United Kingdom

Location

University College London Hospitals NHS Foundation Trust; The London Clinic - Main Hospital

London, W1T 7HA, United Kingdom

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

elacestrant; Alpelisib; Everolimus; ribociclib; palbociclib; capivasertib; abemaciclib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2022
• First Posted: October 3, 2022
• Study Start: January 24, 2023
• Primary Completion (Estimated): December 27, 2026
• Study Completion (Estimated): December 28, 2028
• Last Updated: June 12, 2026

Record last verified: 2026-06

Locations

AR (3); GB (4); US (35); LU (1); BR (5); TU (1); BE (3); KR (3); IL (5); FR (5); AU (1); ES (13); IT (4)