Utidelone Treated for the Recurrent or Metastatic Urothelial Carcinoma

Study Overview
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Brief Summary
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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.

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

Conditions
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Metastatic Urothelial Carcinoma

Intervention / Treatment
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* Drug: utidelone injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 18-70 years Histologically confirmed urothelial carcinoma (pelvis, ureter, bladder, urethra) 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 At least one measurable disease according to the response evaluation criteria in solid tumor (RECIST 1.1) Eastern Cooperative Oncology Group (ECOG) performance status between 0 and 2 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 Life expectancy ≥ 3 months 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. 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: Pregnant or lactating women Suitable for radical means with a chance of cure Patients had received radiation therapy, TKI, or immune checkpoint inhibitor within 2 weeks after the initiation of the study Major organ surgery (excluding needle biopsy) or significant trauma within 4 weeks prior to initial use of the study drug 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; Known active infection with human immunodeficiency virus (HIV), hepatitis B, virus (HBV) or hepatitis C; virus (HCV) Prior allergies to castor oil 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 Patients with mental disorders or poor compliance 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 Subjects with any other conditions were considered unfit for this study determined by the investigator

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Drug: Utidelone
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Utidelone<br>Utidelone Injection: 35 mg/m2/day, IV on day 1-day 5 of each 21 day cycle, administered to enrolled patients with recurrent or metastatic urothelial carcinoma Number of Cycles: until progression or unacceptable toxicity develops or up to 8 cycles. | Drug: utidelone injection<br>* utidelone monotherapy in patients with recurrent or metastatic urothelial carcinoma by utidelone<br>* Other names: UTD1 injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Reflected by percentage of tumor size reduction or regression, assessed by imaging techniques and expressed as Objective Response Rate (ORR） | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Benefit Rate | CR,PR and SD greater than or equal to 24 weeks | 24 weeks | 
| Progression Free Survival (PFS) | Time from date of administration of Utidelone to progression or death | 24 months | 
| Adverse Events and Serious Adverse Events Safety | The incidence of grade ≥3 adverse reactions and the improvement of quality of life were observed | up to 3 years |