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)
The goal of this clinical trial is to evaluate the efficacy of investigator's choice of chemotherapy, either alone or in combination with everolimus, in treating patients with locally recurrent inoperable or metastatic triple-negative breast cancer, luminal androgen receptor (LAR) subtype with PI3K/AKT/mTOR (PAM) pathway mutation, as the first-line treatment.
• 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:
• Blood routine examination standards should meet: HB≥90g/L (no blood transfusion within 14 days); ANC≥1.5×109/L; PLT≥75×109/L;
∙ 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.