A Study of Trastuzumab and Pyrotinib in HER2 Positive Locally Advanced or Metastatic Urothelial Carcinoma

Inclusion Criteria:

• Sign the informed consent form
• Locally advanced or metastatic histologically confirmed transitional cell carcinoma of the urothelium, including the bladder, urethra, ureter, or renal pelvis
• 18 years and older
• HER2 expression (3+ or 2+) as determined by immunohistochemistry or gene amplification by fluorescent in situ hybridization
• Relapsed from or failed at least one prior standard systemic chemotherapy regimen, including immunotherapy, HER2 ADC durgs, and chemothearpy containing cisplatin, carboplatin, paclitaxel, docetaxel, or gemcitabine
• At least 1 measurable lesion could be evaluated by RECIST v1.1
• Performance status: ECOG 0-1
• Life expectancy more than 12 weeks
• Ejection fraction at least 50% (or lower limit of normal) by echocardiogram
• Good organ function:

Blood routine: hemoglobin ≥80g/L, neutrophil ≥1.5×10^9/L, platelet ≥75×10^9/L; Renal function: creatinine≤1.5×upper limit of normal (UNL) or creatinine clearance ≥50ml/min; Liver function: total bilirubin (TBIL)≤1.5×upper limit of normal (UNL); ALT≤2.5×UNL, AST≤2.5×UNL, ALT≤5×UNL and AST≤5×UNL for patients with liver metastasis

Exclusion Criteria:

• Have received trastuzumab or pyrotinib treatment in the past
• Known to have allergic reactions to any ingredients or excipients of experimental drugs
• Radiotherapy, RFA, interventional therapy or surgery were performed within 28 days before the first medication (except for previous diagnostic biopsy)
• Other active malignant tumors, excluding those who have been disease free for more than 5 years or in situ cancer considered to have been cured by adequate treatment
• Clinically significant ascites
• Brain metastasis or meningeal metastasis with neurological symptoms
• Diabetes was not controlled, defined as HbA1c > 7.5% after anti-diabetic drugs or hypertension was not controlled, defined as systolic / diastolic blood pressure > 140 / 90 mmHg after antihypertensive drug
• Myocardial infarction, severe/unstable angina, New York Heart Association (NYHA) class III or IV congestive heart failure in the past 12 months
• Known to be infected with human immunodeficiency virus (HIV), have acquired immunodeficiency syndrome (AIDS) related diseases, have active hepatitis B or hepatitis C
• Pregnant or nursing
• May increase the risk associated with participation in the study or administration of the study drug or mental illness that may interfere with the interpretation of research results
• There are other serious diseases that the researchers believe patients cannot be included in the study