Ph 2 Elacestrant in ER Positive Uterine Sarcomas

A Phase 2 Study Evaluating the Efficacy of Elacestrant in Patients With Estrogen Receptor Positive Uterine Sarcomas

This study is to evaluate the efficacy and safety of elacestrant, in participants with advanced estrogen receptor (ER)-positive uterine sarcomas. The name of the study drug involved in this research study is:

-Elacestrant (a type of selective estrogen receptor degrader)

Study Overview

• Status: Recruiting
• Conditions: Uterine Sarcoma; Endometrial Stromal Sarcoma; Estrogen Receptor Positive Tumor; Uterine Leiomyosarcoma; ESS; Perivascular Epithelioid Cell Tumors; Uterine Adenosarcoma; Uterine PEComa; uLMS
• Intervention / Treatment: Drug: Elacestrant

Detailed Description

This is a single-arm, open-label, phase 2 study evaluating the efficacy and safety of elacestrant in participants with advanced estrogen receptor (ER)-positive uterine sarcomas. Elacestrant is designed to block estrogen receptors, which may slow down or stop the growth of cancers that rely on estrogen to grow.

The U.S. Food and Drug Administration (FDA) has not approved elacestrant as a treatment for ER positive uterine sarcoma.

The research study procedures include screening for eligibility, in-clinic visits, blood tests, urine tests, Computerized Tomography (CT) scans, Magnetic Resonance Imaging (MRI) scans, or Positron Emission (PET) scans, and electrocardiograms (ECGs).

It is expected that about 30 people will take part in this research study. Stemline-Menarini is supporting this research study by providing the study drug.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Suzanne George, MD; Phone Number: 617-632-5204; Email: suzanne_george@dfci.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
      • Contact: Suzanne George, MD; Phone Number: 877-338-7425

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Participant must have histologically confirmed uterine sarcoma of one of the following subtypes: uterine leiomyosarcoma (uLMS), endometrial stromal sarcoma (ESS), uterine adenosarcoma, or uterine PEComa.

Tumor must have moderate to strong immunohistochemical expression in ≥75% of tumor cells of estrogen receptor (ER) as assessed by institutional pathology review.

Participants must have locally advanced or metastatic disease that is not amenable to surgery.

Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) by chest x-ray or as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam. See Section 12 (Measurement of Effect) for the evaluation of measurable disease.

Age ≥18 years at the time of consent

ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).

Participants must have adequate organ and marrow function as defined below:

Hemoglobin ≥ 8.0 g/dL

absolute neutrophil count ≥1,000/mcL

platelets ≥100,000/mcL

total bilirubin ≤1.5 × institutional upper limit of normal (ULN)

AST(SGOT)/ALT(SGPT) ≤3.0 × institutional ULN (unless liver metastases are present in which case it must be ≤ 5 × ULN)

glomerular filtration rate (GFR) ≥60 mL/min/1.73 m2

Human immunodeficiency virus (HIV)-infected participants on effective non-CYP3A4 interacting (see Section 3.2.3) anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.

For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.

Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.

Participants with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.

Participants must be disease-free of prior invasive malignancies for > 5 years with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix. NOTE: If there is a history of prior malignancy, participants must not be receiving other specific treatment for that cancer.

Participants should have completed prior treatment for their cancer: chemotherapy or radiotherapy must have been completed for greater than 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.

Participants should have recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 1) with the exception of alopecia.

Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.

Participants must have a QTc interval length of below 450 msec. QTc will be calculated via the Fridericia's formula.

Participant must be willing to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

Participant must be able to swallow and maintain pills.

Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) and/or family member available will also be eligible.

Women of childbearing age, women who are made postmenopausal through use of GNRH agonists must agree to use adequate contraception for the duration of protocol treatment and for at least 6 months after the last dose of elacestrant if the risk of conception exists.

Adequate contraception is defined as one highly effective non-hormonal form of contraception or two effective forms of non-hormonal contraception by the participant and/or partner.

Highly Effective Non-Hormonal Contraception

Methods of birth control which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly are considered highly effective forms of contraception.

The following non-hormonal methods of contraception are acceptable:

• True abstinence when this is in line with the preferred and usual lifestyle of the participant. [Periodic abstinence (e.g., calendar, ovulation, symptothermal post-ovulation methods) and withdrawal are not acceptable methods of contraception].
• Male sterilization (with appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). For female participants, the vasectomized male partner should be the sole partner.

OR Effective Non-Hormonal Contraception

Alternatively, two of the following effective forms of contraception may be used instead:

Placement of non-hormonal intrauterine device (IUD) or intrauterine system (IUS). Consideration should be given to the type of device being15used, as there is higher failure rates quoted for certain types, e.g., steel or copper wire.

• Condom with spermicidal foam/gel/film/cream/suppository.
• Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
• The use of barrier contraceptives should always be supplemented with the use of spermicide. Failure rates indicate that, when used alone, the diaphragm and condom are not highly effective forms of contraception. Therefore, the use of additional spermicides does confer additional theoretical contraceptive protection. However, spermicides alone are ineffective at preventing pregnancy when the whole ejaculate is spilled. Therefore, spermicides are not a barrier method of contraception and should not be used alone.

It should be noted that two forms of effective contraception are required. A double barrier method is acceptable, which is defined as condom and occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.

Premenopausal women must have a negative serum or urine pregnancy test. Pregnancy testing does not need to be pursued in female participants who are:

• Age > 60 years; or
• Age < 60 with intact uterus and amenorrhea for 12 consecutive months or more AND estrogen (estradiol) levels within postmenopausal range; or
• Documented Status-post bilateral oophorectomy, total hysterectomy, or bilateral tubal ligation

Women must be postmenopausal, which is defined as any of the following:

• Age ≥ 60 years
• Age < 60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) and FSH, and estradiol in the postmenopausal range per local normal range
• Premenopausal women must be on GnRH agonist prior to study entry are eligible. Women in this group MUST remain on the GnRH agonist for the duration of protocol treatment.
• Status-post bilateral oophorectomy - After adequate healing post-surgery

Exclusion Criteria:

Participants who are receiving any other investigational agents.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to elacestrant.

Rapidly progressive, symptomatic, visceral spread of disease placing participant at risk of

life- threatening complications in the short term.

Participants with uncontrolled intercurrent illness, including but not limited to active infection, uncontrolled diabetes, cardiac disease, hypertension or conditions that in the opinion of the investigator would compromise participant safety or study participation

Participants with psychiatric illness/social situations that would limit compliance with study requirements.

Treatment with strong CYP3A inducers/inhibitors within 2 weeks before first study treatment administration or five elimination half-lives, whichever is longest and cannot be replaced. See Appendix B for a list of medications that are CYP3A inducers/inhibitors.

Female participants who are pregnant or nursing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Elacestrant; 30 participants will be enrolled and will complete the following: Baseline visit; Cycle 1 through End of Treatment (28 day cycles)--Days 1 - 28: predetermined dose of Elacestrant 1x daily; End of treatment visit; 30 day post-treatment follow up; Long term follow every 3 months	Drug: Elacestrant; Selective estrogen receptor degrader, tablet taken orally per protocol.; Other Names: RAD1901; Elacestrant Dihydrochloride; Elacestrant Hydrochloride; ASYM-122762; RAD1901 Dihydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR is defined as proportion of participants achieving partial response (PR) or better on treatment per the Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1 (Eisenhauer et al. Eur J Ca 2009; section 11.0).	Observed on treatment plus 30 days; Disease assessed on treatment every 8 (+/- 3 days) weeks for the first 14 cycles, then every 12 (+/- 3 days) weeks thereafter with longest follow-up estimated as 12 months.
Treatment-Related Grade 3-4 Adverse Event (AE) Rate	Percentage of participants who experience an AE of grade 3 or 4 with treatment attribution of possible, probable or definite per Common Toxicity Adverse Event Criteria (CTCAE) version 5 on treatment.	Assessed continuously on treatment plus 30 days with longest follow-up estimated as 13 months.

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Collaborators: Stemline Therapeutics, Inc.
• Investigators: Principal Investigator: Suzanne George, MD, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: February 12, 2026
• First Submitted That Met QC Criteria: March 9, 2026
• First Posted (Actual): March 12, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Neoplasms; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms, Complex and Mixed; Endometrial Neoplasms; Endometrial Stromal Tumors; Sarcoma, Endometrial Stromal; Perivascular Epithelioid Cell Neoplasms; Adenosarcoma of the uterus; elacestrant; RAD1901
• Other Study ID Numbers: 25-822

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication
• IPD Sharing Access Criteria: Contact the Beffer office for Dana -Farber Innovations(BODFI) at innovations@dfci.harvard.edu
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No