Upper tract urothelial carcinoma (UTUC) carries a poor prognosis, with conventional GC (gemcitabine plus cisplatin) regimens achieving only a 19% pathological complete response (pCR) rate in the neoadjuvant setting. Antibody-drug conjugates (ADCs) have shown promising results in advanced urothelial carcinoma, Meanwhile the clinical application of traditional cisplatin-based chemotherapy is associated with significant limitations. Therefore, exploring the efficacy and safety of Trastuzumab Rezetecan (an anti-HER2 ADC) combined with gemcitabine in UTUC is of considerable importance. This trial will enroll patients with HER2 2-3+ UTUC. After pathological diagnosis, patients will receive intravenous infusions of gemcitabine and Trastuzumab Rezetecan. The treatment regimen consists of a 21-day cycle: 4 cycles of neoadjuvant therapy, followed by 2 cycles of adjuvant therapy for patients who do not achieve pCR (total of 6 cycles). For patients with suboptimal pathological downstaging after surgery (≥ypT3 or ypN+), combination with immune checkpoint inhibitors (ICIs) is recommended. During the neoadjuvant period, adverse events will be closely monitored. Regular imaging and follow-up assessments will be performed, and events such as disease recurrence, progression, and their corresponding time points will be documented. The primary endpoint is pCR rate. Secondary endpoints include adverse events during the neoadjuvant period, event-free survival (EFS), overall survival (OS).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
54
Gemcitabine 1000 mg/m² is given via intravenous infusion, followed by intravenous administration of trastuzumab rezetecan 4.8 mg/kg 3 hours thereafter. The treatment consists of 4 cycles in total with a 21-day cycle interval. Patients without pathological complete response (pCR) will receive 2 cycles of adjuvant therapy
Gemcitabine 1000 mg/m² is given via intravenous infusion, followed by intravenous administration of trastuzumab rezetecan 4.8 mg/kg 3 hours thereafter. The treatment consists of 4 cycles in total with a 21-day cycle interval. Patients without pathological complete response will receive 2 cycles of adjuvant therapy
After completing four cycles of neoadjuvant therapy, patients undergo radical nephroureterectomy (RNU). The surgical resection typically includes: 1\) The affected kidney (including the perirenal fat capsule); 2) The entire ureter from the renal pelvis to the intramural segment; 3) A bladder cuff around the ureteral orifice; 4) In addition, ipsilateral regional lymph node dissection (e.g., hilar, para-aortic, and paracaval nodes) may be performed depending on tumor stage and clinical indication.
Huanggang Central Hospital
Huanggang, Hubei, China
RECRUITINGJingzhou Central Hospital
Jingzhou, Hubei, China
RECRUITINGTaihe Hospital
Shiyan, Hubei, China
RECRUITINGThe Central Hospital of Wuhan
Wuhan, Hubei, China
RECRUITINGDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technolog
Wuhan, Hubei, China
RECRUITINGRenmin Hospital of Wuhan University
Wuhan, Hubei, China
RECRUITINGZhongnan Hospital of Wuhan University
Wuhan, Hubei, China
RECRUITINGHubei Cancer Hospital
Wuhan, Hubei, China
RECRUITINGXiangyang Central Hospital
Xiangyang, Hubei, China
RECRUITINGYichang Central People's Hospital
Yichang, Hubei, China
RECRUITINGPathological Complete Response (pCR)
Defined as the absence of residual viable tumor cells (ypT0N0) in RNU specimens. Assessed post surgery. Method: A central pathology review committee performs review of slides from all eligible patients. Two senior uropathologists (associate professor level or above) read independently; consensus is final, otherwise a third senior pathologist adjudicates blindly. ypT and ypN are recorded.
Time frame: Within 1 week after completion of radical nephroureterectomy
Treatment Related Adverse Events During Neoadjuvant Therapy
The patients will be evaluated according to CTCAE 5.0 during neoadjuvant therapy. Assessed from the first cycle to 4 weeks after the last cycle, with comprehensive tests each cycle, a scheduled visit 1 week after the last dose of each cycle, and immediate evaluation upon any alert or complaint. Method: Uniform site training, structured eCRF recording of AE terms, dates, grades, relatedness, actions, outcomes. An independent Clinical Endpoint Committee conducts centralized review of all Grade ≥3 events for final adjudication.
Time frame: The period starting from the first administration of neoadjuvant therapy and extending through 4 weeks following the last dose.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.