Evaluation of Epalrestat in Metastatic Triple-negative Breast Cancer

This is a phase II,single center,prospective, single arm clinical trials. The objective is to evaluate the efficacy and safetyof Epalrestat in the treatment of metastatic triple negative breast.Primary endpoint is 16-week clinical benefit rate (CBR).

• Epalrestat (Drug), also known as Tanglin (Yangtze River Pharmaceutical Group), China: Epalrestat 50mg tid added to standard chemotherapy treatment

Primary outcomes

• Progression-free survival (PFS) [30 months]: the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse

Secondary outcomes

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [30 months]: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
• Overall Survival [3 years]: OS is measured from the date of randomization to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date.

Sex: Female, ages: 18 Years to 70 Years

Inclusion Criteria:

* Female ≥ 18 years, ≤70 years.
* Minimum life expectancy 16 weeks
* Histologicalconfirmation of hormone receptor negative and HER2 negative breast cancer(IHC:ER -, PR-) on primary tumour at diagnosis/on biopsy of metastasis
* Clinical or histological confirmation of metastatic or locally advanced disease not amenable to curative surgical resection
* ECOG 0-2 with no deterioration over previous 2 weeks Measurable disease
* Adequate bone marrow and organ function
* Availability of archival tumour sample or fresh biopsy Informed consent
* Normal organ function

Exclusion Criteria:

* Last dose chemotherapy, immunotherapy targeted therapy, biological therapy or tumour embolisation <21 days prior to study treatment
* Last dose of palliative radiotherapy <7 days prior to study treatment
* Rapidly progressive visceral disease not suitable for further therapy
* Spinal cord compression or brain/meningeal metastases unless asymptomatic, treated and stable and not requiring steroids for ≥ 4 weeks study treatment
* Major surgery (excluding placement of vascular access) within 4 weeks before study treatment
* Evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, or active infection including hepatitis B, hepatitis C and HIV
* With the exception of alopecia, any unresolved toxicities from previous therapy greater than CTCAE grade 1 before study treatment
* Elevated ALP in absence of bone metastasis
* Evidence of dementia, altered mental status or any psychiatric condition that would prohibit understanding or rendering of informed consent
* Participation in another study with investigational product during last 30 days
* Inability or unwillingness to comply with study procedures, including inability to take regular oral medication

• zhongyu yuan, M.D., Principal investigator, Sun Yat-sen University