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

Running, not enrolling · Phase 1/Phase 2

Conditions studied: Breast Cancer, Metastatic Breast Cancer

In brief

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.

Key facts

Study ID

NCT05563220

Run by

Stemline Therapeutics, Inc.

People needed

435

Starts

2023-01-24

Expected to finish

2028-12-28

Last updated by the study team

2026-06-12

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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)
• 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.
• Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation by local laboratory assessment.
• 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.

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.
• 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.
• 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.
• 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.
• 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.
• Evidence of ongoing alcohol or drug abuse as assessed by the investigator.
• Any severe medical or psychiatric condition that, in the Investigator's opinion, would preclude the participant's participation in a clinical study.

Where it is running

• Mayo Clinic - Arizona — Phoenix, Arizona, United States
• Highlands Oncology Group — Springdale, Arkansas, United States
• City of Hope National Medical Center — Duarte, California, United States
• OPN Healthcare (Los Alamitos Location) — Los Alamitos, California, United States
• Cedars Sinai — Los Angeles, California, United States
• UCLA UCLA Hem/Onc - Clinical Research Unit — Los Angeles, California, United States
• UCSF Helen Diller Family Comprehensive Cancer Center — San Francisco, California, United States
• TOI Clinical Research — Whittier, California, United States
• Rocky Mountain Cancer Centers — Lone Tree, Colorado, United States
• George Washington Cancer Center — Washington D.C., District of Columbia, United States
• Advent Health (Florida Hospital) - Altamonte Springs — Altamonte Springs, Florida, United States
• Mayo Clinic - Jacksonville — Jacksonville, Florida, United States
• Northwestern Feinberg Scholl of Medicine Prentice Women's Hospital — Chicago, Illinois, United States
• MD Alliance for Multispecialty Research, LLC — Merriam, Kansas, United States
• Johns Hopkins School of Medicine — Baltimore, Maryland, United States
• Massachusetts General Hospital — Boston, Massachusetts, United States
• Dana Farber Cancer Institute — Boston, Massachusetts, United States
• Barbara Ann Karmanos Cancer Institute — Detroit, Michigan, United States
• Mayo Clinic - Rochester — Rochester, Minnesota, United States
• Washington University School of Medicine in St. Louis — St Louis, Missouri, United States
• Astera Cancer Care — East Brunswick, New Jersey, United States
• Summit Medical Group — Florham Park, New Jersey, United States
• Cooperman Barnabas Medical Center — New Brunswick, New Jersey, United States
• NYU Langone Health — New York, New York, United States
• Dothan Hematology and Oncology — Dothan, Alabama, United States

Full record on ClinicalTrials.gov

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