A Study of Mitoxantrone Hydrochloride Liposome Injection in Advanced Recurrent or Metastatic Breast Cancer

A Randomized, Open-label, Positive-controlled, Single-institutional, Phase Ⅱ of Mitoxantrone Hydrochloride Liposome Injection in Advanced Recurrent or Metastatic Breast Cancer

The hypothesis of this clinical research study is to discover if the study drug Mitoxantrone Hydrochloride Liposome Injection can shrink or slow the growth of advanced recurrent or metastatic breast cancer

Mitoxantrone Hydrochloride Liposome Injection is a kind of anthraquinone compounds, and its antineoplastic effect has been viewed in preclinical tests. The investigator's phase Ⅰstudy has shown that the drug's toxicity is manageable and the tolerable does is 20 mg/m2. The hypothesis of this clinical research study is to discover if the study drug Mitoxantrone Hydrochloride Liposome Injection can shrink or slow the growth of advanced recurrent or metastatic breast cancer. The safety of Mitoxantrone Hydrochloride Liposome Injection will also be studied. Patients physical state, symptoms, changes in the size of the tumor, and laboratory findings obtained while on-study will help the research team decide if Mitoxantrone Hydrochloride Liposome Injection is safe and effective in advanced recurrent or metastatic breast cancer patients.

Inclusion Criteria:

• Written informed consent prior to study specific screening procedures;
• ≥ 18 and ≤ 75 years of age,female;
• Advanced recurrent or Metastatic breast cancer, comfirmed by histological analysis and/or cytology analysis. Have failed for at least two chemotherapy regimen aimed to the advanced recurrent or metastatic focus;
• Adapted to receive chemotherapy;
• Women diagnosed with human epidermal growth factor receptor negative(HER2-); Women diagnosed with HER2+, and unable to be treated by Anti-HER2+ targeted therapy. HER2- is defined as 0 or 1+ staining on immunohistochemistry or FISH negative for gene amplification. HER2+ is defined as +++ staining on immunohistochemistry or FISH positive for gene amplification;
• Not suitable for endocrine theapy or tolerance to endocrine therapy;
• Have at least one measurable site of disease according to RECIST1.1 criteria;
• If chemotherapy regimens containing anthracycline-based drugs, duration from palindromia to this chemotherapy regimens is not less than 12 mounths;
• ECOG performance status of 0-2, life expectancy of more than 3 mounths;
• Cardiac function is almost normal(NYHA classification is Grade 1, LVEF≥ 50％);
• Sexually active women of childbearing potential must use a medically acceptable form of contraception;
• Adequate hepatic, renal and hematologic functions: leukocyte≥3.0×10^9/L,neutrophils≥1.5×10^9/L,platelets≥75×10^9/L, hemoglobin≥90g/L, serum bilirubin≤1.5×ULN, ALT≤2.5×ULN(5×for liver metastasis),AST≤2.5×ULN(5×for liver metastasis), creatinine clearance rate≤1.5×ULN;

Exclusion Criteria:

• Suffering from serious internal disease, including serious heart attack, cerebrovascular disease, uncontrolled diabetes, uncontrolled hypertension, uncontrolled infection, active peptic ulcer;
• Uncontrolled brain metastases;
• Pregnant or lactating women;
• Mitoxantrone has been used before;
• Anthracycline-based drugs was used after relapse and metastasis;
• The cumulative doses of doxorubicin and epirubicin before inclusion have surpassed 360 mg/m2 and 600 mg/m2, respectively;
• Less than 4 weeks from the last chemotherapy, less than 4 weeks from the last radiotherapy, less than 2 weeks from the last endocrinotherapy; Other antineoplastic drugs need to be used in this study;
• History of anthracycline-based drug allergy;
• History of liposome drug allergy;
• Uncontrolled psychosis or uncontrolled infections disease;
• Unsuited to participate in thsi study judged by investigators;