Clinical trial NCT05954442: Everolimus With Investigator's Choice of Chemotherapy in Advanced Triple-Negative Breast Cancer (TNBC) With Luminal Androgen Receptor (LAR) Subtype
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Triple Negative Breast Cancer
Metastatic Breast Cancer
Mutation
Keywords: triple negative breast cancer
metastatic breast cancer
PI3K/AKT/mTOR mutation
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2023-07-20
Enrollment: 203
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: Eligible participants will be those diagnosed with estrogen receptor (ER)-negative \[Immunohistochemistry (IHC) ER positive \<1% ) , progesterone receptor (PR) negative(IHC PR positive \<1% ) , and human epidermal growth factor receptor 2 (HER2)-negative \[IHC 0 or +; or IHC ++, Fluorescence in situ hybridization (FISH) -\], LAR subtype with PAM pathway mutation locally recurrent inoperable or metastatic breast cancer, who have received no prior chemotherapy, targeted therapy or other treatments.

The study is aimed to evaluate the efficacy of investigator's choice (ICC) of chemotherapy (nab-paclitaxel, capecitabine, eribulin, carboplatin, vinorelbine, or utidelone) either alone or in combination with everolimus. This study aims to see if everolimus plus chemotherapy allows patients to live longer without the cancer getting worse, or simply to live longer, compared to patients receiving investigator's choice of chemotherapy. This study is also looking to see how the treatment and the cancer affects patients' quality of life.

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.

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Approximately 3 years
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: Approximately 3 years
measure: Duration of response (DoR)
timeFrame: Approximately 3 years
measure: Disease control rate (DCR)
timeFrame: Approximately 3 years
measure: Overall survival (OS)
timeFrame: Approximately 3 years
measure: Safety and tolerability
timeFrame: Approximately 3 years
measure: Number of participants with patient reported outcome (PRO)
timeFrame: Approximately 3 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Fudan University
name: Zhimin Shao, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: