A Pivotal Phase II Clinical Trial of Utidelone Injection Plus Capecitabine in HER2-negative Breast Cancer Patients With Brain Metastases

Exclusion Criteria

• •1. Leptomeningeal metastasis confirmed by MRI and/or cerebrospinal fluid cytology.
• •2. Any intracranial lesion thought to require immediate local therapy, including (but not limited to) a lesion in an anatomic site where increase in size or possible treatment-related edema may pose risk to patient (e.g. brain stem lesions).
• •3. Have poorly controlled (\> 1/week) generalized or complex partial seizures, or manifest neurologic progression due to brain metastases notwithstanding CNS-directed therapy.
• •4. Had evidence of intracranial hemorrhage within 3 months before study treatment.
• •5. Had evidence of hemoptysis within 6 months before study treatment. Or bleeding or evidence of coagulopathy within 4 weeks before study treatment.
• •6. Undergone major surgical procedures within 4 weeks or not fully recovered from surgery before study treatment.
• •7. Patients who have received anti-tumor therapies less than 2 weeks before the first dose of investigational product, including endocrine therapy, chemotherapy, radiotherapy, biotherapy, targeted therapy, immunotherapy or antibody-drug conjugate therapy.
• •8. Persistent toxicities caused by previous antitumor therapy (excluding alopecia), not yet improved to CTCAE v5.0 grade ≤ 1 or baseline.
• •9. Patients with neuropathy\> grade 1.
• •10. Known hypersensitivity to any components of the investigational product.
• •11. Known deficiency of dihydropyrimidine dehydrogenase (DPD).
• •12. This applies only to the combination cohort and does not apply to the monotherapy cohort. For patients with previous capecitabine treatment, the prior use of capecitabine meets any of the following criteria: A) The best response during prior capecitabine combination therapy or monotherapy is Progressive Disease (PD); B) Have received capecitabine treatment within 6 months prior to the first study treatment.
• •13. Patients who are pregnant (positive pregnancy test) or lactating.
• •14. Patients with other malignancies over the past 5 years, except for inactive tumors with good prognosis, including resected basal cell and squamous cell carcinoma of the skin, in-situ carcinoma of the cervix, or papillary thyroid cancer.
• •15. Patients who are particpating in other interventional studies or who are receiving other study treatments (patients who have discontinued other investigational treatments and are in follow-up are eligible for enrollement in this study).
• •16. Known active or uncontrolled hepatitis B infection, active syphilis, or HIV infection that is not well controlled; or positive for hepatitis B virus based on the evaluation of results of tests for hepatitis B (HBsAg, anti-HBs, anti-HBc, or HBV DNA) infection at screening.
• •17. With a history of severe or uncontrolled diseases.
• •18. Autoimmune diseases requiring treatment with systemic glucocorticoids.
• •19. Not able to perform contrast-enhanced brain MRI or known contraindications to MRI gadolinium contrast, such as cardiac pacemaker, shrapnel, or eye foreign body.
• •20. Patients with a history of other systemic severe diseases or abnormal laboratory findings that would, in the Investigator's judgment, be inappropriate for this study.