ELAINEIII - An Open Label, Randomized, Multicenter Study Comparing the Efficacy and Safety of the Combination of Lasofoxifene and Abemaciclib to the Combination of Fulvestrant and Abemaciclib for the Treatment of Pre- and Postmenopausal Women and Men With Locally Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation

Studio Clinico

Patologia: Neoplasie della mammella

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: Sì

Fase di studio: III

Linee di trattamento: Seconda linea

Criteri di inclusione: 

- Pre- or postmenopausal women or men.
- Locally advanced and/or metastatic ER+ breast cancer with radiological or clinical evidence of progression on an AI in combination with either palbociclib or ribociclib as their first hormonal treatment for metastatic disease.
- Histological or cytological confirmation of ER+/HER2 - disease
- No evidence of progression for at least 6 months on an AI/CDKi combination for advanced breast cancer.
- At least 1 or more ESR1 point mutations in the ESR1 ligand binding domain as assessed in cell- free ctDNA obtained from a blood or breast cancer tissue.
- Locally advanced or metastatic breast cancer with either measurable (according to RECIST 1.1) or non-measurable lesions.
- Subjects may have received 1 cytotoxic chemotherapy regimen in the metastatic disease setting prior to study entry, but must have recovered from chemotherapy acute toxicity excluding alopecia and Grade 2 peripheral neuropathy.
- Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1
- Adequate organ function
- Able to swallow tablets
- Brain metastases are allowed only if the following 4 parameters hold:
    - Asymptomatic,
    - Definitively treated (e.g., radiotherapy, surgery),
    - Not requiring steroids up to 4 weeks before study treatment initiation, AND
    - Central nervous system disease stable for >3 months prior to registration as documented by magnetic resonance imagining (MRI).
- Able to understand and voluntarily sign a written informed consent before any screening procedures.

Criteri di esclusione: 

- Lymphangitic carcinomatosis involving the lung.
- History of Grade 3 or Grade 4 interstitial lung disease (ILD) on previous therapy.
- Visceral crisis in need of cytotoxic chemotherapy as assessed by the investigator.
- Prior progression of disease on abemaciclib, fulvestrant, or other selective estrogen receptor degrader (SERD) therapy.
- Subjects with a known hypersensitivity to fulvestrant or to any of the excipients
- Radiotherapy within 30 days prior to Visit 0 (Day 1) 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 Visit 0 (Day 1). Subjects must have recovered from radiotherapy toxicities prior to Visit 0 (Day 1).
- Known RB1 mutations or deletions that in the opinion of the investigator confer resistance to CDK4/6i. (Screening for RB1 mutation is not required for entry.)
- History of long QTc (Q-T interval corrected for heart rate) syndrome or a QTc of >480 msec.
- History of a pulmonary embolus (PE), deep vein thrombosis (DVT), or any known thrombophilia.
- Lasofoxifene is not recommended for use in subjects with conditions that place them at increased risk for VTEs (such as severe congestive heart failure [CHF] or prolonged immobilization).
- On concomitant strong CYP3A4 inhibitors.
- On strong and moderate CYP3A4 inducers.
- Any significant co-morbidity that would impact the study or the subject's safety, including subjects with significant malabsorption.
- Active systemic bacterial or fungal infection (requiring intravenous [IV] antibiotics or antifungals at the time of initiating study treatment).
- Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).
- 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.
- Positive serum pregnancy test (only if premenopausal).
- Sexually active premenopausal women and men unwilling to use double-barrier contraception.
- Women who are breast feeding
- 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.

Trattamento sperimentale: 

Lasofoxifene in combination with abemaciclib.

Trattamento di controllo: 

Fulvestrant in combination with abemaciclib.

Centri partecipanti

Nord Italia

Centro Italia

Sud Italia e isole

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2023-503708-10 - 2023-503708-10-00

Data di inserimento: 07.08.2024

Promotore

Sermonix Pharmaceuticals Inc.

Principal Investigator ITALIA

Riferimento: Dr. Info non applicabile

Telefono: 00000

Email: na@na.it

Localita: na