An Open-label, Single-arm, Multicenter Phase II Clinical Study to Evaluate Neoadjuvant Gemcitabine Combined With Trastuzumab Rezetecan in HER2-positive Upper Tract Urothelial Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 54
- 试验地点
- 10
- 主要终点
- Pathological Complete Response (pCR)
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The subject voluntarily participates in the study, provides written informed consent, and is able to comply with study procedures and follow-up visits.
- •Aged between 18 and 75 years.
- •Patients diagnosed with upper tract urothelial carcinoma (UTUC) who are candidates for radical nephroureterectomy with bladder cuff excision.
- •Clinical stage T1N0M0 - T2-T4aN1M0 (evaluated by CT/MRI/PET-CT).
- •Histopathology confirms urothelial carcinoma as the predominant component; IHC testing shows HER2 expression of 2+ to 3+.
- •ECOG performance status ≤
- •Laboratory parameters meet all of the following criteria:
- •Absolute neutrophil count ≥ 1.5 × 10⁹/L
- •Platelets ≥ 100 × 10⁹/L; hemoglobin ≥ 90 g/L
- •Total bilirubin ≤ 1.5 × ULN
- •Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) ≤ 2.5 × ULN; serum creatinine ≤ 3 × ULN
- •Cardiac function: New York Heart Association (NYHA) classification < Grade III.
排除标准
- •Received live attenuated vaccines within 4 weeks prior to enrollment or plan to receive such vaccines during the study.
- •Received systemic chemotherapy, anti-PD-1/PD-L1 agents, or HER2-targeted therapy within the previous 6 months.
- •Known hypersensitivity to gemcitabine, Trastuzumab Rezetecan, or any of their excipients.
- •Active, known or suspected autoimmune disease.
- •Known history of primary immunodeficiency.
- •Known history of solid organ allotransplantation or allogeneic hematopoietic stem cell transplantation.
- •Female patients who are pregnant or breastfeeding.
- •Untreated acute or chronically active hepatitis B or hepatitis C infection. Patients receiving antiviral therapy may be considered eligible at the investigator's discretion with ongoing viral load monitoring.
- •Uncontrolled concurrent illnesses, including but not limited to:
- •HIV infection (positive HIV antibody).
- •Severe active infection with inadequate clinical control.
- •Evidence of severe or uncontrolled systemic disease (e.g., severe psychiatric or neurological disorders, epilepsy or dementia; unstable or decompensated respiratory, cardiovascular, hepatic or renal disease; uncontrolled hypertension defined as CTCAE Grade ≥2 hypertension despite medical treatment).
- •Active bleeding, newly diagnosed thromboembolic disease requiring therapeutic anticoagulation, or bleeding diathesis.
- •Diagnosis of another malignant tumor within the past 5 years.
- •Active tuberculosis
结局指标
主要结局
Pathological Complete Response (pCR)
时间窗: Within 1 week after completion of radical nephroureterectomy
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.
次要结局
- Treatment Related Adverse Events During Neoadjuvant Therapy(The period starting from the first administration of neoadjuvant therapy and extending through 4 weeks following the last dose.)
研究者
Zhiquan Hu
Clinical professor
Tongji Hospital