Combining Everolimus with standard therapy for advanced breast cancer

Study of Efficacy of Everolimus Combined With First-line Endocrine Therapy for HR+/HER2- (Open, Randomized, Phase II )

This study is testing if adding Everolimus to standard hormone therapy can help people with advanced breast cancer feel better and live longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 265 (estimated)
• Ages: 18 Years to 75 Years
• Sex: Female
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT05949541 on ClinicalTrials.gov

What this trial studies

This phase II clinical trial investigates the efficacy and safety of Everolimus when combined with standard first-line endocrine therapy for patients with HR+/HER2- SNF1 subtype advanced breast cancer. The study involves a randomized, controlled, open-label design, enrolling 584 patients who have undergone surgery and are classified into subtypes using advanced digital pathology techniques. Participants will be assigned to either the treatment group receiving Everolimus plus endocrine therapy or a control group receiving only standard endocrine therapy, with treatment continuing until disease progression or other specified criteria are met.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with pathologically confirmed HR+/HER2- breast cancer of the SNF1 subtype.

Not a fit: Patients with prior therapy for advanced or metastatic breast cancer or those with other subtypes of breast cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes for patients with advanced HR+/HER2- breast cancer.

How similar studies have performed: Other studies have shown promise in combining targeted therapies with endocrine treatments for breast cancer, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* Patients need to meet all of the following conditions

  * Patients must be ≥18 and ≤ 75 years of age;
  * Pathologically confirmed breast cancer is HR+/HER2- breast cancer (IHC ER \>10%, or/and PR\>10%, HER 0 OR +, if HER2++, FISH negative);
  * SNF1 subtype definition: SNF1 subtype confirmed by digital pathology of H\&E sections;
  * Locally advanced breast cancer (radical local therapy is not possible) or metastatic breast cancer (without using adjuvant CDK4/6 inhibitors in the past, or one year after adjuvant CDK4/6 inhibitor therapy has ended);
  * No prior therapy (chemotherapy, targeted therapy, etc.) for advanced or metastatic breast cancer;
  * Patients with at least one measurable lesion that has not previously received radiation therapy and can be evaluated repeatedly according to RECIST 1.1;
  * The functions of the main organs are basically normal, and the following conditions are met:

    1. Blood routine examination standards should meet: HB≥90g/L (no blood transfusion within 14 days); ANC≥1.5×109/L; PLT≥75×109/L;
    2. Biochemical examination shall meet the following standards: TBIL≤1.5×ULN (upper limit of normal value); ALT and AST≤3 x ULN; In case of liver metastasis, ALT and AST≤5×ULN; Serum Cr ≤1.5×ULN, endogenous creatinine clearance \> 50ml/min (Cockcroft-Gault formula);
  * ECOG performance status 0 or 1; The expected survival is more than 3 months;
  * Fertile female is required to use a medically approved contraceptive during study treatment and for at least 3 months after the last use of the study drug;
  * Patients voluntarily join the study, sign the informed consent, have good compliance, and cooperate with follow-up.

Exclusion Criteria:

* Patients with any of the following conditions were excluded from the study

  * Patients with central nervous system metastasis out of control (symptoms need to use glucocorticoids or mannitol).
  * A history of clinically significant or uncontrolled heart disease, including congestive heart failure, angina pectoris, myocardial infarction within the last 6 months, or ventricular arrhythmia;
  * Radiotherapy, chemotherapy, surgery, other targeted therapy and immunotherapy for advanced HR+/HER2- breast cancer within 4 weeks prior to first administration of drugs used in this study.
  * Pregnant or lactating patients;
  * Other malignancies within the previous 3 years, excluding cured skin basal cell carcinoma and cervical carcinoma in situ;
  * Significant comorbid medical conditions, including mental illnesses that the investigator or sponsor believes would adversely affect the patient's participation in the study;
  * Allergic physique, or known allergic history of the drug components of this program; Or allergic to other monoclonal antibodies;
  * The investigator does not consider the patient suitable for participation in any other circumstances of the study.

Where this trial is running

Shanghai, Shanghai Municipality

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Zhimin Shao, MD,PhD — Fudan University
• Study coordinator: Zhimin Shao, MD, PhD

Conditions Breast Cancer; Advanced Breast Cancer; luminal breast cancer; advanced breast cancer