A Study of Mitoxantrone Hydrochloride Liposome Injection in Patients With Advanced HER2 Negative Breast Cancer

Breast Cancer Clinical Trial

Official title:

A Multicenter, Open-label, Single-arm, Phase II Study of Mitoxantrone Hydrochloride Liposome Injection in Patients With Advanced HER2 Negative Breast Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04927481
• Other study ID #: HE071-CSP-021
• Status: Terminated
• Phase: Phase 2
• Start date: June 11, 2021
• Est. completion date: January 17, 2023

Study information

• Verified date: February 2024
• Source: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multicenter, open-label, single-arm, phase II study to evaluate the safety and efficacy of Mitoxantrone Hydrochloride Liposome in patients with advanced HER2 negative breast cancer.

Description:

This is a multicenter, open-label, single-arm, phase II study to evaluate the safety and efficacy of Mitoxantrone Hydrochloride Liposome in patients with advanced HER2 negative breast cancer. Eligible patients will receive Mitoxantrone Hydrochloride Liposome 20 mg/m2 by an intravenous infusion (IV), every 21 days (q3w, 1 cycle) until disease progression, intolerable toxicity, death, or investigator or patient decision.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 28
• Est. completion date: January 17, 2023
• Est. primary completion date: January 17, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Voluntarily participate in this study and sign informed consent form;

2. Male or female patients aged 18 to 75 years (inclusive);

3. Histologically confirmed diagnosis of HER-2 negative breast cancer (Including immunohistochemistry HER2 0 or 1+, immunohistochemistry HER2 2+ must be confirmed as negative by in situ hybridization);

4. Patients with unresectable locally advanced or recurrent breast cancer with disease progression after first-line or higher chemotherapy;

5. Hormone receptor (HR) negative breast cancer or HR-positive breast cancer that is not suitable for endocrine treatment or is resistant to endocrine treatment.

6. Prior treatment with both an anthracycline (i.e., doxorubicin or epirubicin) and a taxane (i.e., paclitaxel or docetaxel) at least (acceptable for patients not previously treated with anthracyclines due to high risk factors for cardiotoxicity), and four prior chemotherapy regimens at most;

7. At least one measurable lesion according to RECIST v1.1;

8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2;

9. Patients must meet the following criteria prior to treatment (not receiving blood transfusion or growth factors therapy within 14 days before the first administration):

• Absolute neutrophil count (ANC) = 1.5 × 109/L;

• Hemoglobin = 90g / L;

• Platelet count = 90 × 109/L;

• Creatinine =1.5 × upper limit of normal (ULN);

• Total bilirubin = 1.5×ULN;

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3 ×ULN (= 5 ×ULN for liver metastasis);

10. For women of childbearing potential: the serum pregnancy test must be negative, and patients are willing to take adequate contraceptive measures during the treatment period and for at least 6 months after the last dose of the study drug;

11. Good compliance and willingness to cooperate with follow-up visits.

Exclusion Criteria:

1. Patients who have severe allergic reactions to mitoxantrone hydrochloride or liposome preparation ingredients;

2. History of other malignancy within 3 years, except for radical cure of carcinoma in situ of the cervix, basal cell carcinoma or squamous cell carcinoma of the skin;

3. Brain metastases and meningeal metastasis;

4. Patients with active hepatitis B (HBsAg positive with hepatitis B virus DNA = 2000 IU/mL), active hepatitis C (hepatitis C virus antibody positive with hepatitis C virus RNA above the lower limit of detection of the study center), or human immunodeficiency virus (HIV) antibody positive;

5. Life expectancy < 3 months;

6. Previous treatment with the anthracyclines, with the total cumulative dose (doxorubicin equivalent) >350 mg/m2;

7. Adverse events from the previous treatment have not resolved to = Grade 1 based on CTCAE (except for the toxicity without safety risk judged by the investigator, such as alopecia, hyperpigmentation);

8. Impaired cardiac function or serious cardiac disease:

• Long corrected QT interval syndrome or corrected QT interval > 480 ms;

• Complete left bundle branch block, II-III degree atrioventricular block;

• Severe, uncontrolled arrhythmias requiring pharmacological treatment;

• History of chronic congestive heart failure, New York Heart Association = grade 3;

• Cardiac ejection fraction < 50% within 6 months prior to screening;

• Heart valve disease with CTCAE = grade 3;

• ECG evidence of myocardial infarction, unstable angina, severe ventricular arrhythmias, history of severe pericardial disease, and acute ischemic or active conduction system abnormalities within 6 months prior to screening;

9. Uncontrollable hypertension (defined as a measured systolic blood pressure = 160 mmHg or diastolic blood pressure = 100 mmHg under pharmacological control);

10. Active bacterial, fungal or viral infections that require intravenous infusion treatment within 1 week prior to the first dose;

11. Any anticancer treatment (including chemotherapy, radiotherapy, molecular targeted therapy, immunotherapy, endocrine therapy) within 4 weeks prior to the first dose, immunomodulators as adjuvant therapy for malignancy within 2 weeks prior to the first dose, any anti-tumor proprietary Chinese medicine (except for those in the category of supporting and relieving symptoms) within 2 weeks prior to the first dose;

12. Patients who enrolled in any other clinical trials within 4 weeks prior to the first dose;

13. Patients who undergone major surgery within 12 weeks before the first dose, or have a surgical schedule during the study period;

14. Patients with thrombosis or thromboembolism within 6 months prior to screening;

15. Lactating female;

16. Serious and/or uncontrolled medical condition that, in the judgment of the investigator, may affect the patient's participation in this study (including, but not limited to: diabetes not effectively controlled, kidney disease requiring dialysis, severe liver disease, life-threatening autoimmune and bleeding disorders, substance abuse, neurological disorders, etc.);

17. Not suitable for this study as decided by the investigator due to other reasons.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Mitoxantrone Hydrochloride Liposome Injection
Mitoxantrone Hydrochloride Liposome 20 mg/m2, IV, on day 1 of each 21-day cycle (q3w).

Locations

Country	Name	City	State
China	Affiliated Hospital of Hebei University	Baoding	Hebei
China	The second hospital of Jinlin University	Changchun	Jinlin
China	Changsha Kexin Cancer Hospital	Changsha	Hunan
China	Sichuan Cancer Hospital & Institute	Chengdu	Sichuan
China	The second hospital of Dalian Medical University	Dalian	Liaoning
China	Daqing People's Hospital	Daqing	Helongjiang
China	Cancer Center Sun Yat-sen University	Guozhou	Guodong
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Anhui Provincial Hospical	Hefei	Anhui
China	Cancer Hospital of Jiamusi City	Jiamusi	Helongjiang
China	The First Affiliated Hospital of Jinzhou Medical University	Jinzhou	Liaoning
China	The third Hospital of Nanchang	Nanchang	Jiangxi
China	The second people's hospital of neijiang	Neijiang	Sichuan
China	The First hospital of China Medical University	Shenyang	Liaoning
China	The Fourth Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	Shanxi Provincial Cancer Hospital	Taiyuan	Shanxi
China	Tangshan People's Hospital	Tangshan	Hebei
China	Affiliated tumor Hospital of Xinjiang Medical University	Urumqi	Xinjiang
China	The First Affiliated Hospital of Xinjiang Medical University	Urumqi	Xinjiang
China	Hubei Cancer Hospital	Wuhan	Hubei
China	Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology	Wuhan	Hubei
China	Zhongnan Hospital of Wuhan University	Wuhan	Hubei
China	Xingtai People's Hospital	Xingtai	Hebei
China	The First Affiliated Hospital of Xinxiang Medical University	Xinxiang	Henan
China	Yiyang Central Hospital	Yiyang	Hunan
China	Yuncheng Central Hospital	Yuncheng	Shanxi
China	Cancer Hospital of Henan Province	Zhengzhou	Henan
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan
China	Henan Provincial People's Hospital	Zhenzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (ORR)	To investigate the preliminary antitumor efficacy	From the enrollment to the final documentation of response of the last subject(assessed up to 36 months)
Secondary	Disease control rate (DCR)	To investigate the preliminary antitumor efficacy	From the enrollment to the final documentation of response of the last subject(assessed up to 36 months)
Secondary	Duration of response (DoR)	To investigate the preliminary antitumor efficacy	From the enrollment to death,lost to follow-up,withdrawal,or study end,whichever occurred first,assessed up to 36 months
Secondary	Progression-free survival (PFS)	To investigate the preliminary antitumor efficacy	From the enrollment to death,lost to follow-up,withdrawal,or study end,whichever occurred first,assessed up to 36 months
Secondary	Overall survival (OS)	To investigate the preliminary antitumor efficacy	From the enrollment to death,lost to follow-up,withdrawal,or study end,whichever occurred first,assessed up to 36 months
Secondary	Treatment emergent adverse events (TEAEs)	The incidence and severity of adverse events, abnormalities in physical exams, vital sign assessments, clinical laboratory assessments, ultrasonic cardiograms (UCGs) and electrocardiographs (ECGs).	from the administration of the first dose to 28 days after the last dose