Combining Everolimus with Chemotherapy for Advanced Triple-Negative Breast Cancer

An Open, Randomized Phase III Study of Everolimus With Investigator's Choice of Chemotherapy Versus Chemotherapy in The First-Line Treatment of Luminal Androgen Receptor (LAR) Subtype With PI3K/AKT/mTOR Pathway Mutation of Locally Recurrent Inoperable or Metastatic Triple-Negative Breast Cancer (BCTOP-T-M03)

This study is testing if adding everolimus to chemotherapy can help adults with advanced triple-negative breast cancer live longer and feel better.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 203 (estimated)
• Ages: 18 Years to 70 Years
• Sex: Female
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT05954442 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of everolimus in combination with an investigator's choice of chemotherapy for patients with advanced triple-negative breast cancer, specifically those with the luminal androgen receptor subtype and mutations in the PI3K/AKT/mTOR pathway. Participants must be adults aged 18 to 70 with locally recurrent inoperable or metastatic breast cancer who have not received prior chemotherapy or targeted therapy. The study aims to determine if this combination treatment can improve survival and quality of life compared to chemotherapy alone.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with advanced triple-negative breast cancer of the luminal androgen receptor subtype and specific genetic mutations.

Not a fit: Patients who have previously received chemotherapy or targeted therapy for advanced breast cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with advanced triple-negative breast cancer, potentially improving survival rates.

How similar studies have performed: Other studies have shown promise in using targeted therapies like everolimus in combination with chemotherapy for similar cancer types, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* Patients need to meet all of the following conditions

  * Patients must be ≥18 and ≤ 70 years of age;
  * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
  * The expected survival is more than 3 months;
  * Pathologically confirmed breast cancer is triple negative breast cancer (IHC ER \< 1%, PR\<1%, HER2 0 OR +, if HER2++, FISH negative), and LAR subtype with mutation in PAM pathway;
  * Recurrent or metastatic breast cancer; Patients with local recurrence need to be confirmed by the investigator that radical surgical resection is not possible;.
  * No prior therapy (chemotherapy, targeted therapy, etc.) for advanced or metastatic breast cancer;
  * Patients with at least one lesion (measurable and/or unmeasurable) that has not previously received radiation therapy can be accurately evaluated by CT/MRI at baseline 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× upper limit of normal value(ULN); alanine aminotransferase (ALT) and AST≤3 x ULN; In case of liver metastasis, ALT and AST≤5×ULN; Serum Cr ≤1×ULN, endogenous creatinine clearance \> 50ml/min (Cockcroft-Gault formula);
  * Patients have not received radiotherapy, endocrine therapy, molecular targeted therapy, or surgery within 3 weeks prior to study initiation, and have recovered from acute toxic effects of prior treatment (if surgery is present, the wound has fully healed); No peripheral neuropathy or grade I peripheral neurotoxicity;
  * Fertile female are 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 known central nervous system metastasis or history of central nervous system metastasis prior to screening. For patients with clinically suspected central nervous system metastasis, enhanced CT or enhanced MRI must be performed within 28 days before the first dose to rule out central nervous system metastasis.
  * 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;
  * Persistent grade ≥1 adverse events due to previous treatment. The exception to this is hair loss or something the researchers believe should not be ruled out. Such cases should be clearly documented in the investigator's notes;
  * Major surgery was performed within 3 weeks of the first course of trial treatment (except for minor outpatient surgery, such as placement of vascular access);
  * Pregnant or lactating patients;
  * Other malignancies within the previous 5 years, excluding cured cervical carcinoma in situ, skin basal cell carcinoma, or skin squamous cell carcinoma;
  * Inability to swallow, chronic diarrhea and intestinal obstruction, there are many factors affecting drug use and absorption;
  * There is a third space effusion that cannot be controlled by drainage or other methods (such as excessive pleural fluid and ascites);
  * Participated in other anti-tumor drug clinical trials within 4 weeks before taking the study drug for the first time;
  * Long-term unhealed wounds or incomplete healing fractures;
  * Patients with known Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection active phase or hepatitis B DNA≥500, or chronic phase with abnormal liver function;
  * 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 Triple Negative Breast Cancer; Metastatic Breast Cancer; Mutation; triple negative breast cancer; metastatic breast cancer; PI3K/AKT/mTOR mutation