New drug cocktails aim to stall metastatic breast cancer

NCT ID NCT05563220

Disease control Sponsor: Stemline Therapeutics, Inc. Source: ClinicalTrials.gov ↗

First seen Jun 27, 2026 · Last updated Jun 27, 2026

Summary

This study tests a drug called elacestrant combined with other medicines in people with a common type of advanced breast cancer (ER+/HER2-). The goal is to find safe doses and see if these combinations can slow down cancer growth. About 435 adults with metastatic breast cancer will take part.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 1/2

Runs two stages together: safety and dose first, then whether the treatment works.

Participants

About 435 people

The number the study aims to enrol. It can still change while the study runs.

Started

Jan 2023

Expected to finish

Dec 2028

An estimate. End dates often move.

Lead sponsor

A company

The lead sponsor is a pharmaceutical, biotech, or medical-device company.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. Participant 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 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: 1. Age ≥60 years or 2. 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 3. 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. 3. 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. 4. Documented radiological disease progression during or after the most recent therapy. 5. 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. 6. Eastern Cooperative Oncology Group performance status of 0 or 1. 7. Participant has adequate bone marrow and organ function, as defined by the following laboratory values: 1. Absolute neutrophil count ≥1.5 × 10\^9/liter (L) 2. Platelets ≥100 × 10\^9/L 3. Hemoglobin ≥9.0 grams/deciliter (g/dL) 4. Creatinine is ≤ 1.5 x upper limit of normal (ULN) or if creatinine is \> 1.5 x ULN, then creatinine clearance must be ≥50 milliliters/minute based on the Cockcroft-Gault formula. Note: C-G formula: * Creatinine clearance (male) = (\[140-age in years\] × weight in kilograms \[kg\])/ (\[serum creatinine in milligrams/deciliter (mg/dL)\] × 72) * Creatinine clearance (female) = (0.85 × \[140-age in years\] × weight in kg)/ (\[serum creatinine in mg/dL\] × 72) f. Serum albumin ≥3.0 g/dL (≥30 g/L) g. In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 × ULN. If the participant has liver metastases, ALT and AST ≤ 5 × ULN h. Total serum bilirubin \<1.5 × ULN except for participants with Gilbert's syndrome who may be included if the total serum bilirubin is ≤3.0 × ULN or direct bilirubin ≤ 1.5 × ULN. Additional Criteria for the Alpelisib Combination (Phase 1b and Arm A): In general, the prescription information of the respective combination drug should be consulted for instructions/restrictions with respect to interactions with concomitant medications. 1. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation by local laboratory assessment. 2. One or up to two prior hormonal therapies in the advanced or metastatic setting, one of which was in combination with a cyclin-dependent kinase targeting enzymes CDK4 and CDK6 (CDK4/6) inhibitor. Additional Criteria for the Everolimus Combination (Phase 1b and Arm B), the Abemaciclib Combination (Arm C), the Ribociclib Combination (Phase 1b and Arm C), and the Palbociclib Combination (Phase 1b): One or up to two prior hormonal therapies in the advanced or metastatic setting, one of which was in combination with a CDK4/6 inhibitor. Additional Criteria for the Palbociclib Combination (Arm D), the Abemaciclib Combination (Arm D), and the Ribociclib Combination (Arm D): One or up to two prior hormonal therapies in the advanced or metastatic setting. Additional Criteria for Capivasertib Combination (Phase 1b and Arm E): Recruitment in this combination will occur only in countries where capivasertib is locally approved and available. 1. PIK3CA/AKT1/PTEN-alteration as detected by an FDA and/or locally approved test (local result). 2. One or up to two prior hormonal therapies in the advanced or metastatic setting or participants who have radiological evidence of breast cancer recurrence or progression within 12 months from the end of adjuvant treatment with endocrine therapy, as these participants are considered as first line relapsed participants. Prior CDK4/6i treatment is allowed but not required. Exclusion Criteria: 1. 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. 2. 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%. 3. Prior chemotherapy or elacestrant in the advanced/metastatic setting. 4. Participants with known germline BRCA mutation without prior treatment with a PARP inhibitor before study entry. 5. Prior therapy with elacestrant or other investigational selective estrogen receptor degraders, or investigational alike agents such as selective estrogen receptor modulators, selective estrogen receptor covalent antagonists, complete estrogen receptor antagonists, and proteolysis-targeting chimeras, in the metastatic setting. Prior treatment with fulvestrant is not exclusionary, except for Arm E, as it is an approved medication. 6. 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. 7. 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. 8. Documented pneumonitis/interstitial lung disease prior to Cycle 1 Day 1. 9. Major surgery within 28 days before starting trial therapy. 10. 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. 11. Known intolerance to elacestrant or any of its excipients. 12. 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. 13. Men or women who do not agree to abstain from donating sperm or ova, or to use a highly effective method of contraception, 28 days prior, during the course of the treatment period and for 120 days after the last dose of study treatment. 14. Participant is currently receiving or received any of the following medications prior to first dose of trial therapy: • Anti-cancer therapy within 14 days (28 days for anticancer antibody based treatment) or 5 half-lives, whichever is shorter. Please note: Toxicity from prior therapy must be resolved to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 Grade ≤1, except alopecia and peripheral sensory neuropathy (Grade ≤2). * Known strong or moderate inducers or inhibitors of cytochrome P450 (CYP) 3A4 within 14 days or 5 half-lives, whichever is shorter, (refer to https://drug-interactions.medicine.iu.edu/maintable.aspx or https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers). * Herbal preparations/medications within 7 days. These include, but are not limited to, St. John's wort, kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone, yohimbe, saw palmetto, and ginseng. * Vaccination, including but not limited to vaccination against COVID-19, during the 7 days prior to starting trial therapy. 15. Evidence of ongoing alcohol or drug abuse as assessed by the investigator. 16. Any severe medical or psychiatric condition that, in the Investigator's opinion, would preclude the participant's participation in a clinical study. Additional Criteria for the Alpelisib Combination (Phase 1b and Arm A): 1. Prior therapy with alpelisib or any other phosphoinositide 3-kinase (PI3K) inhibitor. 2. Type 1 diabetes or uncontrolled type 2 diabetes (fasting plasma glucose level of \>140 mg/dL \[7.7 millimole (mmol)/L\], or glycosylated hemoglobin \[HbA1c\] level of \>6.4%). 3. Known intolerance to alpelisib or any of its excipients. 4. Participant is currently receiving or received drugs known to be a breast cancer resistant protein inhibitor (for example, curcumin, cyclosporine A, eltrombopag, febuxostat, fostamatinib, rolapitant, teriflunomide) within 14 days or 5 half-lives, whichever is shorter, prior to first dose of trial therapy (refer to Table 5.2 of https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers). 5. Participant has ongoing osteonecrosis of the jaw from previous or concurrent treatment with bisphosphonates or denosumab Additional Criteria for the Everolimus Combination (Phase 1b and Arm B): 1. Prior therapy with everolimus. 2. Known intolerance to everolimus or any of its excipients. Additional Criteria for the Abemaciclib Combination (Arm C): 1. Prior therapy with abemaciclib in the advanced or metastatic setting. Adjuvant therapy with abemaciclib is also exclusionary. 2. Known intolerance to abemaciclib or any of its excipients. 3. History of deep vein thrombosis or pulmonary embolism (unless on anticoagulation), cerebrovascular accident, or myocardial infarction, in the past 6 months. Participants on anticoagulation should have been on a stable dose for at least 3 months prior to enrollment. Additional Criteria for the Ribociclib Combination (Phase 1b and Arm C): 1. Prior therapy with ribociclib in the advanced or metastatic setting. Prior adjuvant therapy with ribociclib is also exclusionary. 2. Known intolerance to ribociclib or any of its excipients. 3. QTcF interval corrected by Fridericia formula (QTcF) values ≥450 milliseconds (msec). 4. Participants who already have or who are at significant risk of developing QTc prolongation, including participants with: * Long QT syndrome * Uncontrolled or significant cardiac disease including recent (6 months) myocardial infarction, congestive heart failure, unstable angina, and brady-arrhythmias * Electrolyte abnormalities (K+, Ca++, Phos, Mg++) ≥Grade 1 5. Participant is currently receiving or received drugs known to prolong QT interval within 14 days or 5 half-lives, whichever is shorter, before the first dose of trial therapy. Additional Criteria for the Palbociclib Combination (Phase 1b): 1. Prior therapy with palbociclib in the advanced or metastatic setting. 2. Known intolerance to palbociclib or any of its excipients Additional Criteria for the Palbociclib Combination (Arm D): 1. Prior therapy with a CDK4/6i in the metastatic setting. 2. Known intolerance to palbociclib or any of its excipients. Additional Criteria for the Abemaciclib Combination (Arm D): 1. Prior therapy with any CDK4/6i. 2. Known intolerance to abemaciclib or any of its excipients. Additional Criteria for Ribociclib Combination (Arm D): 1. Prior therapy with a CDK4/6i in the advanced or metastatic setting. 2. Known intolerance to ribociclib or any of its excipients. 3. QTcF values ≥450 msec. 4. Participants who already have or who are at significant risk of developing QTc prolongation, including participants with: * Long QT syndrome * Uncontrolled or significant cardiac disease including recent (6 months) myocardial infarction, congestive heart failure, unstable angina, and brady-arrhythmias * Electrolyte abnormalities (K+, Ca++, Phos, Mg++) ≥Grade 1 5. Participant is currently receiving or received drugs known to prolong QT interval within 14 days or 5 half-lives, whichever is shorter, before the first dose of trial therapy. Additional Criteria for Capivasertib Combination (Phase 1b and Arm E): Recruitment in this combination will occur only in countries where capivasertib is locally approved and available. 1. Prior treatment with any of the following: AKT, PI3K and mammalian target of rapamycin inhibitors and, for Arm E, fulvestrant. 2. Known intolerance to capivasertib or any of its excipients. 3. QTcF values ≥470 msec or factors that increase the risk of corrected QT interval (QTc) prolongation or risk of arrhythmic events such as heart failure, hypokalemia, potential for torsades de pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age, or any concomitant medication known to prolong the QT interval. 4. Clinically significant abnormalities of glucose metabolism as defined by any of the following: Participants with diabetes mellitus type 1; participants with diabetes mellitus type 2 requiring insulin treatment or participants with HbA1c level of \>8.0% (63.9 mmol/mol).

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Conditions

The condition(s) this trial relates to.

breast cancer breast carcinoma breast neoplasm estrogen-receptor positive breast cancer

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Breast cancer Metastatic breast cancer

Contacts and locations

Locations

ACCG - Hospital Araujo Jorge

Goiânia, 74605-070, Brazil
ASST degli Spedali Civili di Brescia

Brescia, 25123, Italy
Abdurrahman Yurtaslan Oncology Hospital

Ankara, 0*6200, Turkey (Türkiye)
Advent Health (Florida Hospital) - Altamonte Springs

Altamonte Springs, Florida, 32701, United States
Asan Medical Center

Seoul, 05505, South Korea
Astera Cancer Care

East Brunswick, New Jersey, 08816, United States
Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States
Cancer Care Northwest

Spokane Valley, Washington, 99216, United States
Cedars Sinai

Los Angeles, California, 90048, United States
Cemaic - Centro De Especialidades Medicas Ambulatorias E Investigacion Clinica

Córdoba, X5008HHW, Argentina
Centre Hospitalier De L'Ardenne

Libramont, 06800, Luxembourg
Centre Hospitalier Lyon SUD- HCL

Lyon, 69495, France
Centre Hospitalier Universitaire (Chu) De Toulouse - Institut Universitaire Du Cancer De Toulouse-Oncopole (Iuct-Oncopole) (Institut Claudius Regaud)

Toulouse, 31059 Cedex 09, France
Centre de Cancérologie du Grand Montpellier

Montpellier, 34070, France
Centre de Cancérologie du Grand Montpellier

Rouen, 76038 Cedex 1, France
Centro Gaucho Integrado de Oncologia; Hematologia; Ensino e Pesquisa - Hospital Mae de Deus/AESC

Porto Alegre, 90850-170, Brazil
Centro Medico Austral

Buenos Aires, C1017AAS, Argentina
Centro Oncologico Riojano Integral (Cori)

La Rioja, 01122, Argentina
City of Hope National Medical Center

Duarte, California, 91010, United States
Clinica Neoplasias Litoral

Itajaí, 88301-220, Brazil
Complejo Hospitalario Universitario A Coruna

A Coruña, 15006, Spain
Cooperman Barnabas Medical Center

New Brunswick, New Jersey, 08901, United States
Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States
Davidoff Rabin Medical Center

Petah Tikva, 49100, Israel
Dothan Hematology and Oncology

Dothan, Alabama, 36303, United States
Fundacion Instituto Valeciano De Oncologia

Valencia, 46009, Spain
Gangnam Severance Hospital

Seoul, 06273, South Korea
George Washington Cancer Center

Washington D.C., District of Columbia, 20037, United States
Grand Hôpital de Charleroi - Site Notre Dame

Charleroi, 06000, Belgium
Highlands Oncology Group

Springdale, Arkansas, 72762, United States
Hospital Arnau De Vilanova

Valencia, 46015, Spain
Hospital Clinic Barcelona

Barcelona, 08036, Spain
Hospital Clinico San Carlos

Madrid, 28040, Spain
Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain
Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain
Hospital Sao Lucas da PUCRS

Porto Alegre, 90610-000, Brazil
Hospital Sirio-Libanes (HSL) - Centro De Oncologia - Sao Paulo

São Paulo, 01308-050, Brazil
Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain
Hospital Universitario 12 de Octubre

Madrid, 28041, Spain
Hospital Universitario La Paz

Madrid, 28046, Spain
Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain
IOB Madrd Institute of Oncology Hospital Beata Maria Ana de Jesus

Madrid, 28007, Spain
Institut Gustave-Roussy-Umr 981

Villejuif, 94805, France
Institut Jules Bordet

Anderlecht, 01070, Belgium
Istituto Europeo di Oncologia (IEO)

Milan, 20141, Italy
Istituto Nazionale Tumori "Fondazione PASCALE"

Naples, 80131, Italy
Johns Hopkins School of Medicine

Baltimore, Maryland, 21287, United States
MD Alliance for Multispecialty Research, LLC

Merriam, Kansas, 66204, United States
MD Anderson Cancer Center Texas

Houston, Texas, 77030, United States
Macquarie University

Sydney, 2113, Australia
Massachusetts General Hospital

Boston, Massachusetts, 02114, United States
Mayo Clinic - Arizona

Phoenix, Arizona, 85054, United States
Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States
Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States
NEXT Madrid

Pozuelo de Alarcón, 28223, Spain
NYU Langone Health

New York, New York, 10016, United States
North Middlesex University Hospital

London, N18 1QX, United Kingdom
Northwest Medical Specialties (Nwms) - Puyallup - Medical Oncology (Rainier Hematology-Oncology)/Exigent Research Network; LLC

Tacoma, Washington, 98405, United States
Northwestern Feinberg Scholl of Medicine Prentice Women's Hospital

Chicago, Illinois, 60611, United States
OPN Healthcare (Los Alamitos Location)

Los Alamitos, California, 90720, United States
Ospedale Infermi di Rimini - Azienda Unita Sanitaria Locale Della Romagna

Rimini, 47923, Italy
Rambam Heath

Haifa, 352408, Israel
Rocky Mountain Cancer Centers

Lone Tree, Colorado, 80124, United States
Samson Assuta Ashdod University Hospital - The Institute of Oncology

Ashdod, 7747629, Israel
Sarah Cannon Research Institute / Tennessee Oncology

Nashville, Tennessee, 37203, United States
Sarah Cannon Research Institute UK; Ltd

London, W1G 6AD, United Kingdom
Seoul National University Bundang Hospital

Seongnam-si, 13620, South Korea
Shaare Zedek Medical Center

Jerusalem, 9103102, Israel
Sheba Medical Center; Center Israel

Ramat Gan, 5265601, Israel
Summit Medical Group

Florham Park, New Jersey, 07932, United States
TOI Clinical Research

Whittier, California, 90603, United States
Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States
The Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, L7 8YA, United Kingdom
UCLA UCLA Hem/Onc - Clinical Research Unit

Los Angeles, California, 90095, United States
UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158, United States
UT Health San Antonio

San Antonio, Texas, 78229, United States
Universitaire Ziekenhuizen (Uz) Leuven - Campus Gasthuisberg - Multidisciplinair Borstcentrum (Multidisciplinary Breast Center) (Mbc)

Leuven, 03000, Belgium
University College London Hospitals NHS Foundation Trust; The London Clinic - Main Hospital

London, W1T 7HA, United Kingdom
University of WI - Carbone Cancer Center (Phase II only)

Madison, Wisconsin, 53792, United States
Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States
Virginia Oncology Associates

Norfolk, Virginia, 23502, United States
W&IH of RI Breast Health Center of Women and Infants Hospital of Rhode Island

Providence, Rhode Island, 02905, United States
Washington University School of Medicine in St. Louis

St Louis, Missouri, 63110, United States

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