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Evaluation of Lasofoxifene Combined With Abemaciclib in Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation (ELAINEII)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT04432454
Recruitment Status : Active, not recruiting
First Posted : June 16, 2020
Last Update Posted : June 7, 2022
Information provided by (Responsible Party):
Sermonix Pharmaceuticals Inc.

Brief Summary:
This is an open-label, multicenter, single-arm safety study evaluating the safety and tolerability of the lasofoxifene and abemaciclib combination for the treatment of pre- and postmenopausal women with locally advanced or metastatic ER+/HER2- breast cancer who have disease progression on first and/or 2nd lines of hormonal treatment for metastatic disease and have an ESR1 mutation.

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Drug: Lasofoxifene and abemaciclib (VERZENIO (R)). Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Multicenter Study Evaluating the Safety of Lasofoxifene in Combination With Abemaciclib for the Treatment of Pre- and Postmenopausal Women With Locally Advanced or Metastatic ER+/HER2- Breast Cancer and Have an ESR1 Mutation ( ELAINEII )
Actual Study Start Date : September 29, 2020
Estimated Primary Completion Date : November 2022
Estimated Study Completion Date : November 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Abemaciclib

Arm Intervention/treatment
Experimental: Treatment
Women who have locally advanced or metastatic ER+/HER2- breast cancer and disease progression on first and/or 2nd lines of hormonal treatment for metastatic disease and have an ESR1 mutation
Drug: Lasofoxifene and abemaciclib (VERZENIO (R)).
Lasofoxifene 5 mg given once a day orally and abemaciclib 150 mg given twice a day orally.

Primary Outcome Measures :
  1. Safety and tolerability of the combination of lasofoxifene and abemaciclib as measured by number of adverse events (AEs), severity of AEs and mortality due to AEs at every scheduled visit. [ Time Frame: All subjects enrolled in the study will be treated until documented disease progression or until withdrawal for any reason. Safety and tolerability will be assessed from enrollment up to 24 months. ]
    AEs will be assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.

Secondary Outcome Measures :
  1. Progression free survival (PFS) [ Time Frame: Up to 24 months ]
    PFS is defined as the time from the date of entry into the study to the earliest date of first documented progression or death due to any cause.

  2. Clinical benefit rate (CBR) [ Time Frame: 24 weeks or longer ]
  3. Objective response rate (ORR) [ Time Frame: All subjects enrolled in the study will be treated until documented disease progression or until withdrawal for any reason. ORR will be assessed up to 24 months. ]
  4. Duration of response (DoR) [ Time Frame: DoR will be assessed up to 24 months. ]
    DoR is from the date of first documented response (CR or PR) to the date of first documented progression of disease or death due to any cause.

  5. Time to response [ Time Frame: Time to response will be assessed up to 24 months. ]
    From the date of entry into the study to the date of first documented response (CR or PR).

  6. Steady-state pharmacokinetics (PK) sampling for lasofoxifene and abemaciclib concentrations as well as abemaciclib's 3 major metabolites [ Time Frame: Baseline and pre-dose at every visit starting at Visit 0 (Day 1) through Visit 4 (Week 8) and at the Final/ET visit if this occurred prior to Week 8 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Pre- or postmenopausal.

    Postmenopausal women are defined as:

    1. ≥ 60 years of age with no vaginal bleeding over the prior year, or
    2. < 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
    3. 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.
  2. If possible, a biopsy of metastatic breast cancer tissue should be obtained to provide histological or cytological confirmation of ER+/HER2- disease as assessed by a local laboratory, according to American Society of Clinical Oncology/College of American Pathologists 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 is ER+ and HER2-.
  3. Locally advanced and/or metastatic breast cancer with radiological or clinical evidence of progression on the first or 2nd lines of hormonal therapy for metastatic disease. Progression may have occurred on no more than 2 of the following endocrine treatments for metastatic breast cancer: an aromatase inhibitor (AI) and/or fulvestrant either as monotherapy or in combination with any commercially approved CDKi; and/or the combination of fulvestrant and everolimus; and/or the combination of fulvestrant and alpelisib; and/or tamoxifen; and/or the combination of exemestane/everolimus. (Note: before starting study treatment, subjects should have stopped any CDKi for at least 21 days)
  4. Subjects must have had no evidence of progression for at least 6 months during their first hormonal treatment for advanced breast cancer.
  5. At least one or more of the following ESR1 point mutations as assessed in cell-free circulating tumor DNA (ctDNA) obtained from a blood or tissue sample: Y537S, Y537C, D538G, E380Q, S463P, V534E, P535H, L536H, L536P, L536R, L536Q, or Y537N. Note: the Sponsor's blood ctDNA assay must be used but tissue sequencing (if done) may be done by a validated commercial laboratory.

    Note: A positive ESR1 mutation in tissue or ctDNA using a validated commercial assay if done prior or at the time of disease progression is acceptable to meet this entry criteria. However, blood for ctDNA must still be obtained for genomic analyses using the sponsor's ctDNA assay.

  6. Locally advanced or metastatic breast cancer with either measurable (according to RECIST 1.1) or non-measurable lesions.
  7. Subjects may have received one cytotoxic chemotherapy regimen for metastatic disease as well as those who received one cytotoxic chemotherapy regimen in the neo-adjuvant or adjuvant setting prior to entry into the trial can be enrolled but must be free of all chemotherapy acute toxicity excluding alopecia and Grade 2 peripheral neuropathy before study entry. A washout period of at least 21 days is required between last chemotherapy dose and entry into the study.
  8. Stable breast cancer metastasis to the brain is allowed as long as the subject has received radiotherapy and not demonstrated any evidence of brain metastasis progression for at least 3 months after the completion of radiotherapy.
  9. ECOG performance score of 0 or 1.
  10. Adequate organ function as shown by:

    1. absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
    2. platelet count ≥ 100,000 cells/mm3
    3. hemoglobin ≥ 8.0 g/dl
    4. ALT and AST levels ≤ 3 upper limit of normal (ULN) or ≤ 5 in the presence of liver metastasis
    5. total serum bilirubin ≤ 1.5 X ULN (≤ 3 X ULN for subjects known to have Gilbert Syndrome)
    6. alkaline phosphatase level ≤ 3 ULN
    7. creatinine clearance of 40 ml/min or greater as calculated by the Cockcroft-Gault formula
    8. International normalized ratio (INR) and activated partial thromboplastin (aPTT) < 2.0 X ULN
  11. Able to swallow tablets.
  12. Able to understand and voluntarily sign a written informed consent before any screening procedures.

Exclusion Criteria:

  1. Lymphangitic carcinomatosis involving the lung.
  2. Visceral crisis in need of cytotoxic chemotherapy as assessed by the investigator.
  3. Radiotherapy within 30 days prior to entry into the study 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 entry into the study. Subjects must have recovered from radiotherapy toxicities prior to entry into the study.
  4. Subjects with known inactivating RB1 mutations or deletions (Screening for RB1 mutation is not required for entry).
  5. History of long QTC syndrome or a QTC of > 480 msec.
  6. 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.
  7. Subjects on concomitant strong CYP3A4 inhibitors such as clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir.
  8. Subjects on strong and moderate CYP3A4 inducers such as amprenavir, barbiturates, carbamazepine, clotrimazole, dexamethasone, efavirenz, ethosuximide, griseofulvin, modafinil, nevirapine, oxcarbazepine, phenobarbital, phenytoin, chronic prednisone treatment, primidone, rifabutin, rifampin, rifapentine, ritonavir, topiramate.
  9. Any significant co-morbidity that would impact the study or the subject's safety. Since CDKi have reported the occurrence of interstitial lung disease (ILD), subjects with a history of ILD and those with severe dyspnea at rest or requiring oxygen therapy should not enter the study
  10. Subject has an active systemic bacterial or fungal infection (requiring intravenous [IV] antibiotics at the time of initiating study treatment).
  11. History of a positive human immunodeficiency virus (HIV) or hepatitis B virus (HBV) test. Screening is not required for enrollment.
  12. Subjects with hepatitis C virus (HCV) at Screening who still have a viral load. Subjects previously treated and achieved a HCV cure (no viral load) can be entered into the study
  13. 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.
  14. Positive serum pregnancy test (only if premenopausal).
  15. History of non-compliance to medical regimens.
  16. Unwilling or unable to comply with the protocol.
  17. Current participation in any clinical research trial involving an investigational drug or device within the last 30 days.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04432454

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United States, Alabama
University of Alabama at Birmingham (UAB) - Comprehensive Cancer Center
Birmingham, Alabama, United States, 35294-3300
United States, Arizona
Yuma Regional Medical Center
Yuma, Arizona, United States, 85364
United States, California
Compassionate Cancer Care Med Group - Clinic Aid USA - Fountain Valley
Fountain Valley, California, United States, 92708
St. Joseph Health
Santa Rosa, California, United States, 95403
United States, Florida
Mayo Jacksonville
Jacksonville, Florida, United States, 32224
United States, Illinois
Illinois Cancer Care
Peoria, Illinois, United States, 61704
United States, Indiana
Beacon Health System Memorial Regional Cancer Center
South Bend, Indiana, United States, 46601
United States, Minnesota
Mayo Clinic Rochester
Rochester, Minnesota, United States, 55905
United States, New Jersey
New Jersey Cancer Care, PA
Belleville, New Jersey, United States, 07109
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210
United States, Texas
Mary Crowley Cancer Research
Dallas, Texas, United States, 75230
MD Anderson Cancer Center
Houston, Texas, United States, 77030-4009
Oncology Consultants, P.A.
Houston, Texas, United States, 77030
United States, Virginia
Hematology Oncology Associates of Fredericksburg
Fredericksburg, Virginia, United States, 22408
United States, Washington
Northwest Medical Specialists, PLLC (NWMS)
Tacoma, Washington, United States, 98405
Sponsors and Collaborators
Sermonix Pharmaceuticals Inc.
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Responsible Party: Sermonix Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT04432454    
Other Study ID Numbers: SMX 20-001
First Posted: June 16, 2020    Key Record Dates
Last Update Posted: June 7, 2022
Last Verified: June 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases