Efficacy and Safety of Utidelone Capsule and Utidelone Injection in Patients With HER-2 Negative Advanced Breast Cancer

A Randomized,Controlled Phase III Study on Efficacy and Safety of Utidelone Capsule and Utidelone Injection in Patients With HER-2 Negative Advanced Breast Cancer

This study is a randomized controlled study.The primary objective is to evaluate the Progression-Free Survival(PFS) of Utidelone Capsule combined with Capecitabine compared with Utidelone Injection combined with Capecitabine in patients with HER-2 negative advanced breast cancer.

Inclusion Criteria:

1. Patients who have fully understood the objectives, content, process of the study and possible adverse events, voluntarily serves as a subject and signs the informed consent form.
2. Subjects aged ≥18 and ≤75.
3. Male or female subjects with ECOG performance status scored 0-1.
4. Patients who were diagnosed with HER-2 negative advanced breast cancer by histopathology.
5. Patients with locally advanced,recurrent,or metastatic breast cancer.
6. Patients who had received chemotherapy regimens, including at least one taxanes or anthracyclines.
7. Patients with hormone receptor positive should have disease progression after endocrine therapy.
8. At least one measurable lesion present according to RECIST 1.1 criteria.
9. Expected survival time ≥ 12 weeks
10. Baseline routine blood tests is normal.
11. Liver and kidney function test results are normal.
12. Fertile males and females of childbearing potential must agree to use effective contraception (so do their partners, using hormonal or barrier contraception, or abstinence) during the study and within at least 6 months after the last dose. The blood or urine pregnancy test for female patients of childbearing potential prior to enrollment must be negative.

Exclusion Criteria:

1. Patients who have received non-investigational anti-tumor therapies within 4 weeks prior to study drug administration.
2. Patients who have used Capecitabine or Utidelone within 6 months prior to randomization.
3. Patients with breast cancer with CNS metastases leptomeningeal metastases.
4. Patients with uncontrollable bone metastases,existing or recent risk of fracture, recent need for surgery or local radiotherapy, or other critical conditions.
5. Patients with uncontrollable pleural effusion,pericardial effusion or ascites requiring repeated drainage(once a month or more)
6. Patients with serious cardiovascular disease.
7. Patients with mental illnesses which are hard to control, patients who lack legal capacity or have limited legal capacity.
8. Patients with gastrointestinal disorders affecting oral administration.
9. Patients with active infections and need systemic therapy currently.
10. Patients with peripheral neuropathy grade≥2 during randomization.
11. Patients with toxicity grade ≥2 which caused by prior anti-tumor therapy.(NCI-CTCAE 5.0,except for what is considered no safety risk such as alopecia by investigator.）
12. Patients who have received any major surgery(except for diagnostic procedures such as biopsy）,or have sustained major trauma within 4 weeks to randomization;or is expected to undergo major surgery during the treatment.
13. Patients who have received radiotherapy within 2 weeks to randomization.
14. Patients who have received interventional therapy in another clinical trail or have received other investigational treatments.
15. Patients with other malignant tumor within 5 years to randomization excluding curatively treated cervical carcinoma in situ, cutaneous basal cell carcinoma or squamous cell carcinoma, and papillary thyroid carcinoma.
16. Patients with allergy of caster oil:patients with previous fluorouracil medication history with severe allergy or known dihydropyrimidine dehydrogenase (DPD) deficiency;
17. Pregnant or lactating patients.
18. Patients who, in the opinion of the investigator, are not suitable to participate in this study.