Clinical Study of Mitoxantrone Hydrochloride Liposome Injection Combined With Capecitabine in Patients With HER-2 Negative Advanced Breast Cancer
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- MTD of mitoxantrone hydrochloride liposome
研究概览
简要总结
To evaluate the dose-limiting toxicity of mitoxantrone hydrochloride liposome combined with capecitabine in patients with HER-2 negative advanced breast cancer who have received at least first-line treatment, explore the maximum tolerated dose (MTD) of mitoxantrone hydrochloride liposome, and determine the recommended phase II dose (RP2D).
详细描述
This is a single-center, open-label, phase I dose-increasing study following the "3+3" principle, which planned to enroll a maximum of 48 clinically confirmed patients with advanced HER-2 negative breast cancer who have received at least first-line treatment, to explore the MTD of mitoxantrone hydrochloride liposome.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patients fully understand and voluntarily participate in this study and sign the informed consent form.
- •Age ≥18 and ≤70 years, Female.
- •Histopathologically confirmed HER-2 negative breast cancer (Immunohistochemical HER-2 0/1+ or immunohistochemical HER-2 2+ that had to be confirmed as negative by in situ hybridization).
- •Hormone receptor (HR) negative, HR positive but ineligible for endocrine therapy, or HR positive but resistant to endocrine therapy.
- •Recurrent or metastatic breast cancer that have failed at least one line of chemotherapy or ADC. And previous endocrine therapy was not counted.
- •Previous treatment with taxanes and/or anthracyclines.
- •Relapse occurred no less than 12 months after the last dose of an anthracycline-containing adjuvant chemotherapy regimen.
- •Have at least one measurable disease according to RECIST 1.
- •ECOG (Eastern Cooperative Oncology Group) performance status of 0-
- •Good bone marrow function (no blood transfusion or growth factor support within 2 weeks before the first dose of trial medication): WBC≥3.0×10^9/L, ANC ≥1.5×10^9/L, PLT ≥75×10^9/L, Hb≥90g/L.
- •Pregnancy tests were negative, and patients of childbearing age committed to use effective contraception or abstinence from sex from the start of the study until 6 months after the last study dose.
- •Expected survival time greater than 3 months.
- •Good compliance and willingness to cooperate with follow-up visits.
排除标准
- •Patients have one of the following conditions in the previous anti-tumor treatments:
- •Previous treatment with mitoxantrone or mitoxantrone liposome:
- •Previous treatment with doxorubicin or epirubicin (total cumulative dose of doxorubicin>350mg/m^2, total cumulative dose of epirubicin>700mg/m^2);
- •Has received anti-tumor treatment (including chemotherapy, targeted therapy, hormone therapy, taking traditional Chinese medicine with anti-tumor activity, etc.) or participated in other clinical trials and received clinical trial drugs within 4 weeks before the first use of the study drugs.
- •Abnormal heart function, including:
- •Long QTc syndrome or QTc interval > 480ms;
- •Complete left bundle branch block, degree II or III atrioventricular block;
- •Severe, uncontrolled arrhythmias requiring medical treatment;
- •New York Heart Association grade ≥ II;
- •A history of myocardial infarction, unstable angina, severe unstable ventricular arrhythmia or any other arrhythmia requiring treatment, a history of clinically significant pericardial disease, or ECG evidence of acute ischemia or active conduction system abnormalities within 6 months before recruitment.
- •Previous or current concurrent malignancy other than breast cancer.
- •Have any serious and/or uncontrolled medical conditions that in the judgment of the investigator may affect the patient's participation in the study (including advanced infection, uncontrolled diabetes or hypertension, severe liver disease, etc.).
- •Have uncontrolled brain metastases.
- •Chronic hepatitis B (HBsAg or HBcAb positive and HBV DNA≥1000IU/mL), chronic hepatitis C (HCV antibody positive and HCV RNA higher than the lower limit of the detection value of the research center), or HIV antibody positive.
- •Participants who are known to be allergic to the active or other components of the study treatment.
- •Pregnant or lactating women.
- •A history of severe neurological or psychiatric illness.
- •Participants who were judged by the investigator to be unsuitable for this study.
研究组 & 干预措施
Experimental: 3-week arm
Patients will receive mitoxantrone hydrochloride liposome combined with capecitabine therapy in a 3-week treatment cycle.
干预措施: Mitoxantrone hydrochloride liposome (Drug)
Experimental: 3-week arm
Patients will receive mitoxantrone hydrochloride liposome combined with capecitabine therapy in a 3-week treatment cycle.
干预措施: Capecitabine (Drug)
Experimental: 4-week arm
Patients will receive mitoxantrone hydrochloride liposome combined with capecitabine therapy in a 4-week treatment cycle.
干预措施: Mitoxantrone hydrochloride liposome (Drug)
Experimental: 4-week arm
Patients will receive mitoxantrone hydrochloride liposome combined with capecitabine therapy in a 4-week treatment cycle.
干预措施: Capecitabine (Drug)
结局指标
主要结局
MTD of mitoxantrone hydrochloride liposome
时间窗: At the end of Cycle 1 (each cycle is 21 days or 28 days)
To evaluate the tolerability of mitoxantrone hydrochloride liposome combination regime
次要结局
- Objective response rate (ORR)(21 or 28 days after the last dose)
- Disease control rate (DCR)(21 or 28 days after the last dose)
- Progression-free survival (PFS)(one year after the last dose)
- Safety: Hematologic and non-hematologic toxicities (NCI CTCAE v5.0)(From the initiation of the first dose to 21 or 28 days after the last dose)