Mitoxantrone Hydrochloride Liposome Combined With Capecitabine in Patients With HER-2 Negative Advanced Breast Cancer
Study Details
Study Description
Brief Summary
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Experimental: 3-week arm Patients will receive mitoxantrone hydrochloride liposome combined with capecitabine therapy in a 3-week treatment cycle. |
Drug: Mitoxantrone hydrochloride liposome
Drug: Mitoxantrone hydrochloride liposome (16 mg/m^2, 18 mg/m^2, 20 mg/m^2 and 22 mg/m^2) will be administered by intravenous infusion on day 1 in a 3-week treatment cycle.
Drug: Capecitabine
Capecitabine (1000 mg/m^2) will be administered orally in a 3-week treatment cycle, twice a day from day 1 to day 14 of each cycle.
|
| Experimental: Experimental: 4-week arm Patients will receive mitoxantrone hydrochloride liposome combined with capecitabine therapy in a 4-week treatment cycle. |
Drug: Mitoxantrone hydrochloride liposome
Mitoxantrone hydrochloride liposome (16 mg/m^2, 18 mg/m^2, 20 mg/m^2 and 22 mg/m^2) will be administered by intravenous infusion on day 1 in a 4-week treatment cycle.
Drug: Capecitabine
Capecitabine (825 mg/m^2) will be administered orally in a 4-week treatment cycle, twice a day from day 1 to day 21 of each cycle.
|
Outcome Measures
Primary Outcome Measures
- MTD of mitoxantrone hydrochloride liposome [At the end of Cycle 1 (each cycle is 21 days or 28 days)]
To evaluate the tolerability of mitoxantrone hydrochloride liposome combination regime
Secondary Outcome Measures
- 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]
To identify the incidence of AE and SAE in clinical trial
- Objective response rate (ORR) [21 or 28 days after the last dose]
To evaluate the efficacy of anti-tumor
- Disease control rate (DCR) [21 or 28 days after the last dose]
To evaluate the efficacy of anti-tumor
- Progression-free survival (PFS) [one year after the last dose]
To evaluate the efficacy of anti-tumor
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients fully understand and voluntarily participate in this study and sign the informed consent form.
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Age ≥18 and ≤70 years, Female.
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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).
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Hormone receptor (HR) negative, HR positive but ineligible for endocrine therapy, or HR positive but resistant to endocrine therapy.
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Recurrent or metastatic breast cancer that have failed at least one line of chemotherapy or ADC. And previous endocrine therapy was not counted.
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Previous treatment with taxanes and/or anthracyclines.
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Relapse occurred no less than 12 months after the last dose of an anthracycline-containing adjuvant chemotherapy regimen.
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Have at least one measurable disease according to RECIST 1.1.
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ECOG (Eastern Cooperative Oncology Group) performance status of 0-1.
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LVEF≥50%.
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Good bone marrow function (no blood transfusion or growth factor support within 2 weeks before the first dose of trial medication): WBC≥3.0×109/L, ANC ≥1.5×109/L, PLT ≥75×10^9/L, Hb≥90g/L.
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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.
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Expected survival time greater than 3 months.
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Good compliance and willingness to cooperate with follow-up visits.
Exclusion Criteria:
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Patients have one of the following conditions in the previous anti-tumor treatments:
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Previous treatment with mitoxantrone or mitoxantrone liposome:
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Previous treatment with doxorubicin or epirubicin (total cumulative dose of doxorubicin>350mg/m2, total cumulative dose of epirubicin>700mg/m2);
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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.
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Abnormal heart function, including:
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Long QTc syndrome or QTc interval > 480ms;
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Complete left bundle branch block, degree II or III atrioventricular block;
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Severe, uncontrolled arrhythmias requiring medical treatment;
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New York Heart Association grade ≥ II;
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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.
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Previous or current concurrent malignancy other than breast cancer.
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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.).
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Have uncontrolled brain metastases.
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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.
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Participants who are known to be allergic to the active or other components of the study treatment.
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Pregnant or lactating women.
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A history of severe neurological or psychiatric illness.
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Participants who were judged by the investigator to be unsuitable for this study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cancer Hospital Chinese Academy of Medical Sciences | Beijing | Beijing | China |
Sponsors and Collaborators
- Cancer Institute and Hospital, Chinese Academy of Medical Sciences
- CSPC Ouyi Pharmaceutical Co., Ltd.
Investigators
- Principal Investigator: Binghe Xu, PHD, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CSPC-DED-BC-K01