Utidelone Treated for the Recurrent or Metastatic Urothelial Carcinoma

Utidelone Treated for the Recurrent or Metastatic Urothelial Carcinoma After Prior Chemotherapy: a Open-label, Multicenter Phase II Study (UTRUST)

This study is a open-label, multicenter, phase II study to evaluate the efficacy and safety of utidelone in the recurrent or metastatic urothelial carcinoma after prior chemotherapy.

Inclusion Criteria:

1. Patients aged 18-70 years

2. Histologically confirmed urothelial carcinoma (pelvis, ureter, bladder, urethra)

3. Recurrent (unresectable) or metastatic urothelial carcinoma, Patients with primary urothelial carcinoma, mixed with other tissue components, failed or intolerant to standard treatment, and failed to receive neoadjuvant chemotherapy combined with immunotherapy for 12 months were allowed

4. At least one measurable disease according to the response evaluation criteria in solid tumor (RECIST 1.1)

5. Eastern Cooperative Oncology Group (ECOG) performance status between 0 and 2

6. The results of patient's laboratory biochemistry tests are as follows:

   • Normal blood routine within 1 week before enrollment (no blood transfusion or hematopoietic stimulating factor therapy within 14 days) :Hemoglobin(Hb) ≥ 90g/L; Neutrophil count (ANC) > 1.5x109 / L; Platelet count (PLT) ≥ 75×109/L
   • Renal function: serum creatinine ≤ normal upper limit (ULN)
   • Liver and renal function:

   Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT)≤ 3 x ULN, total bilirubin ≤1.5 x ULN, Serum creatinine :≤1.5× ULN or creatinine clearance (Ccr)≥50 ml/min

7. Life expectancy ≥ 3 months

8. Male or female patients of child-producing potential must agree to use double barrier contraception, oral contraceptives, or avoidance of pregnancy measures during the study and for 3 months after the last day of treatment.

9. Females of childbearing potential must have a negative serum pregnancy test at screening and must agree to use double barrier contraception, oral contraceptives, or avoidance of pregnancy measures during the study and for 6 months after the last day of treatment.

Exclusion Criteria:

1. Pregnant or lactating women
2. Suitable for radical means with a chance of cure
3. Patients had received radiation therapy, TKI, or immune checkpoint inhibitor within 2 weeks after the initiation of the study
4. Major organ surgery (excluding needle biopsy) or significant trauma within 4 weeks prior to initial use of the study drug
5. Received an investigational agent, chemotherapy, biological therapy, hormonal therapy, targeted therapy, or radiotherapy within 30 days prior to commencing study treatment, or have not recovered from all treatment-related toxicities to Common Toxicity Criteria (CTC) Grade less than or equal to 1, except for alopecia.CTCAE v.5.0 Grade greater than or equal to 2 peripheral neuropathy;
6. Known active infection with human immunodeficiency virus (HIV), hepatitis B, virus (HBV) or hepatitis C; virus (HCV)
7. Prior allergies to castor oil
8. Patients with symptomatic central nervous system metastases are not permitted, except for those with stable and asymptomatic brain metastases who have completed cranial irradiation, and have at least one measurable lesion outside the brain. Radiotherapy should be completed within 4 weeks prior to the registration
9. Patients with mental disorders or poor compliance
10. A history of severe cardiovascular and cerebrovascular diseases, including but not limited to severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention, degree II-III atrioventricular block, etc. The mean QTcF obtained from three 12-lead ECG examinations at rest was >470ms. Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular events occurred within 6 months before the first dose of dose. Clinically uncontrolled hypertension
11. Subjects with any other conditions were considered unfit for this study determined by the investigator