Evaluation of Lasofoxifene Versus Fulvestrant in Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation

NCT03781063 | Completed Phase 2 FDA Drug

• 1 other identifier: SMX 18001
• Study Type: interventional
• Target: 100
• Locations: 3 countries
• Sites: 51

Brief Summary

This is an open label, randomized, multicenter study evaluating the activity of lasofoxifene relative to fulvestrant for the treatment of pre- and postmenopausal women with locally advanced or metastatic ER+/HER2- breast cancer with an acquired ESR1 mutation and who have disease progression on an aromatase inhibitor (AI) in combination with a cyclin dependent kinase (CDK) 4/6 inhibitor. The primary objective is to evaluate the progression free survival (PFS) of 5 mg lasofoxifene relative to fulvestrant for the treatment of pre- and postmenopausal women with locally advanced or metastatic estrogen receptor positive (ER+)/human epidermal growth factor 2 negative (HER2-) breast cancer with an estrogen receptor 1 (ESR1) mutation. The secondary objectives are to evaluate:

1. 1.Clinical benefit rate (CBR) and Objective Response Rate (ORR)
2. 2.Duration of response
3. 3.Time to response
4. 4.Overall Survival (OS)
5. 5.Pharmacokinetics of lasofoxifene
6. 6.Quality of life (QoL): Quality of Life (QoL): vaginal assessment scale (VAS) and vulvar assessment scale (VuAS) questionnaires
7. 7.Safety of lasofoxifene
8. 8.Response to various ESR1 mutation (Y537S, Y537C, D538G, E380Q, S463P, V534E, P535H, L536H, L536P, L536R, L536Q, or Y537N).

Conditions

Locally Advanced or Metastatic Breast Cancer

Keywords

Locally Advanced Breast Cancer; Metastatic Breast Cancer; Lasofoxifene; Fulvestrant; ER+/HER2; ESR1 mutation

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  PFS is defined as the interval from the date of randomization to the earlier date of first documented radiographic progression or death due to any cause

  through study completion, an average of 1 year

Secondary Outcomes (4)

• Clinical Benefit Rate (CBR)

  through study completion, an average of 1 year

• Objective Response Rate (ORR)

  through study completion, an average of 1 year

• Overall Survival (OS)

  through study completion, an average of 1 year

• Incidence of Adverse Events (AEs) and Serious AEs

  through study completion, an average of 1 year

Study Arms (2)

Lasofoxifene

EXPERIMENTAL

5 mg/d of oral lasofoxifene

Drug: Lasofoxifene

Fulvestrant

ACTIVE COMPARATOR

500 mg fulvestrant intramuscular (IM)

Drug: Fulvestrant

Interventions

Lasofoxifene DRUG

Estrogen receptor antagonist antineoplastic agent

Lasofoxifene

Fulvestrant DRUG

Estrogen receptor antagonist antineoplastic agent

Fulvestrant

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Pre- and Postmenopausal women
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pre- or postmenopausal.
• Postmenopausal women are defined as:
• ≥60 years of age with no vaginal bleeding over the prior year, or
• \<60 years with "premature menopause" or "premature ovarian failure" manifest itself with secondary amenorrhea for at least 1 year and follicle stimulating hormone (FSH) and estradiol levels in the postmenopausal range according to institutional standards, or
• surgical menopause with bilateral oophorectomy. Note: premenopausal women who meet all of the other entry criteria must be maintained on ovarian suppression (such as Lupron) during the study and subjects counseled to use appropriate contraception to prevent pregnancy.
• If possible, a biopsy of metastatic breast cancer tissue will be obtained to provide histological or cytological confirmation of ER+ and HER2- disease as assessed by a local laboratory, according to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines, using slides, paraffin blocks, or paraffin samples. If a biopsy is not possible, the ER and HER2 status from the tissue obtained at the time of the original diagnosis must confirm that the subject's cancer is ER+ and HER2-.
• Locally advanced or metastatic breast cancer with radiological or clinical evidence of progression on an AI in combination with a CDK 4/6 inhibitor for advanced breast cancer with demonstrated prior sensitivity to endocrine therapy (recurrence or progression after at least 12 months of treatment in the metastatic setting).
• Locally advanced or metastatic breast cancer with either measurable (according to RECIST 1.1) or non-measurable lesions.
• At least one or more of the following point ESR1 mutations as assessed in cell-free circulating tumor DNA (ctDNA) obtained from a blood (plasma) or tissue sample: Y537S, Y537C, D538G, E380Q, S463P, V534E, P535H, L536H, L536P, L536R, L536Q, or Y537N. The ctDNA sample collection must be obtained within 30 days prior to randomization to determine eligibility and baseline. Note: a prior genomic test confirming that the subject has an ESR1 mutation can be used to determine eligibility; however, an ESR1 sample must also be collected within 30 days of randomization.
• Subjects who have not received cytotoxic chemotherapy or those who have received one cytotoxic chemotherapy regimen in the neo-adjuvant or adjuvant setting prior to entry into the trial and/or no more than one chemotherapy regimen for metastatic breast cancer. Subjects must be free of all chemotherapy acute toxicity excluding alopecia and Grade II peripheral neuropathy before study entry.
• ECOG performance score of 0 or 1.
• Adequate organ function as shown by:
• absolute neutrophil count (ANC) \>/=1,500 cells/mm3
• platelet count ≤100,000 cells/mm3
• hemoglobin \>/=9.0 g/dl

You may not qualify if:

• Prior use of everolimus or other mammalian target of rapamycin (mTOR) inhibitor or phosphoinositide 3-kinase inhibitor (PI3K) inhibitors is excluded unless discontinued to reasons other than disease progression.
• Presence of brain metastasis.
• Lymphangitic carcinomatosis involving the lung.
• Impending visceral crisis in need of cytotoxic chemotherapy as assessed by the investigator.
• Radiotherapy within 30 days prior to randomization except in case of localized radiotherapy for analgesic purposes or for lytic lesions at risk of fracture, which can then be completed within 7 days prior to randomization. Subjects must have recovered from radiotherapy toxicities prior to randomization.
• History of long QTC syndrome or a QTC of \>480 ms.
• History of a pulmonary embolus (PE) or deep vein thrombosis (DVT) within the last 6 months or any known thrombophilia. Subjects stable on anti-coagulants for maintenance are eligible as long as the DVT and/or PE occurred \>6 months prior to enrollment and there is no evidence for active thrombosis. The use of low dose ASA is permitted.
• Any significant co-morbidity that would impact the study or the subject's safety.
• History of a positive human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) at Screening. Subjects cured of hepatitis C (no viral load) are eligible.
• History of malignancy within the past 5 years (excluding breast cancer), except basal cell or squamous cell carcinoma of the skin curatively treated by surgery, or early stage cervical cancer.
• History of vaginal bleeding over the last year unless it is documented that the bleeding was due to non-uterine causes (e.g. vaginal atrophy).
• Uncontrolled hypertension defined as sitting systolic pressure \>160 mm Hg or diastolic pressure \>100 mm Hg at Screening.
• History of non-compliance to medical regimens.
• Unwilling or unable to comply with the protocol.
• Current participation in any clinical research trial involving an investigational drug or device within the last 30 days.

Sponsors & Collaborators

• Sermonix Pharmaceuticals Inc.: lead
• Linical Accelovance Group: collaborator

Study Sites (51)

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

Yuma Regional Medical Center (JIT)

Yuma, Arizona, 85364, United States

Location

City of Hope Comprehensive Cancer

Duarte, California, 91010, United States

Location

Compassionate Care Research Group

Fountain Valley, California, 92708, United States

Location

UCSF Cancer Center

San Francisco, California, 94115, United States

Location

Rocky Mountain Cancer Centers

Longmont, Colorado, 80501, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

Miami Cancer Institute

Miami, Florida, 33176, United States

Location

Ocala Oncology Center (JIT)

Oscala, Florida, 34474, United States

Location

Florida Cancer Specialists

Tallahassee, Florida, 32308, United States

Location

The Bond Clinic Cancer & Research Center.

Winter Haven, Florida, 33880, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Hawaii Cancer Care (JIT)

Honolulu, Hawaii, 96813, United States

Location

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Illinois Cancer Care (JIT)

Peoria, Illinois, 61615, United States

Location

Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

Beacon Health (JIT)

South Bend, Indiana, 46601, United States

Location

University of Louisville / James Graham Brown Cancer Center

Louisville, Kentucky, 40202, United States

Location

FMH James M Stockman Cancer Institute (JIT)

Frederick, Maryland, 21702, United States

Location

Mayo Clinic

Rochester, Minnesota, 55902, United States

Location

Hattiesburg Clinic Hematology/Oncology

Hattiesburg, Mississippi, 39401, United States

Location

Saint Luke's Cancer Institute

Kansas City, Missouri, 64111, United States

Location

HCA Midwest Health

Kansas City, Missouri, 64132, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Comprehensive Cancer Centers of Nevada (JIT)

Las Vegas, Nevada, 89128, United States

Location

New Jersey Cancer Care and Blood Disorders (JIT)

Belleville, New Jersey, 07203, United States

Location

Summit Medical Group (JIT)

Florham Park, New Jersey, 07932, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

TriHealth Cancer Institute

Cincinnati, Ohio, 45220, United States

Location

The Ohio State University - Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Ohio Health (JIT)

Columbus, Ohio, 43221, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Sanford Cancer Center (JIT)

Sioux Falls, South Dakota, 57104, United States

Location

Tennessee Oncology Chattanooga

Chattanooga, Tennessee, 37404, United States

Location

West Cancer Center

Germantown, Tennessee, 38138, United States

Location

Tennessee Oncology/SCRI

Nashville, Tennessee, 37203, United States

Location

Mary Crowley Cancer Research (JIT)

Dallas, Texas, 75230, United States

Location

Oncology Consultants (JIT)

Houston, Texas, 77024, United States

Location

Utah Cancer Specialists (JIT)

Salt Lake City, Utah, 84102, United States

Location

Peninsula Cancer Institute

Newport News, Virginia, 23601, United States

Location

The Ottawa Hospital

Ottawa, Ontario, K1H8L6, Canada

Location

Sunnybrook Health Sciences Center

Toronto, Ontario, M4N3M5, Canada

Location

CIUSSS de Saguenay-Lac-Saint Jean

Chicoutimi, Quebec, G7H5H6, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T1E2, Canada

Location

McGill University Health Centre

Montreal, Quebec, H4A3J1, Canada

Location

Soroka University Medical Center

Beersheba, Israel, 84101, Israel

Location

Hadassah Ein Kerem Medical Center

Jerusalem, Israel, 9112001, Israel

Location

Rabin Medical Center

Petah Tikva, Israel, 49100, Israel

Location

Sheba Medical Center

Ramat Gan, Israel, 52656021, Israel

Location

Related Publications (1)

• Goetz MP, Bagegni NA, Batist G, Brufsky A, Cristofanilli MA, Damodaran S, Daniel BR, Fleming GF, Gradishar WJ, Graff SL, Grosse Perdekamp MT, Hamilton E, Lavasani S, Moreno-Aspitia A, O'Connor T, Pluard TJ, Rugo HS, Sammons SL, Schwartzberg LS, Stover DG, Vidal GA, Wang G, Warner E, Yerushalmi R, Plourde PV, Portman DJ, Gal-Yam EN. Lasofoxifene versus fulvestrant for ER+/HER2- metastatic breast cancer with an ESR1 mutation: results from the randomized, phase II ELAINE 1 trial. Ann Oncol. 2023 Dec;34(12):1141-1151. doi: 10.1016/j.annonc.2023.09.3104.

  PMID: 38072514 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Lasofoxifene; Fulvestrant

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Paul V. Plourde, MD

  Sermonix Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: open label, randomized, parallel-group, multicenter study

Study Record Dates

• First Submitted: December 14, 2018
• First Posted: December 19, 2018
• Study Start: September 20, 2019
• Primary Completion: May 8, 2025
• Study Completion: May 8, 2025
• Last Updated: January 28, 2026

Record last verified: 2026-01

Locations

US (42); CA (5); IL (4)