Neoadjuvant Gemcitabine Plus Trastuzumab Rezetecan in HER2-positive UTUC
ConditionUTUC
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorZhiquan Hu
About this trial
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).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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).
Disqualifiers
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.
Trial design
Design model
Single group
Treatments tested in this trial
Trastuzumab Rezetecan
DrugGemcitabine 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
DrugGemcitabine 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
Radical nephroureterectomy
Procedure/SurgeryAfter 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.
Treatment groups
54 Participants
are divided into 1 treatment groupGroup A: Trastuzumab Rezetecan plus Gemcitabine GroupExperimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
Pathological 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 nephroureterectomySecondary outcomes
1
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.Other outcomes
1
Event-Free Survival
Defined as time from neoadjuvant start to first occurrence of: disease progression (local/regional recurrence, distant metastasis, or definite clinical progression); death from any cause; initiation of new anti-cancer therapy due to progression or toxicity. Censored at last known event-free assessment. Assessed at scheduled visits. Method: A central follow-up unit conducts structured symptom queries; any suspected event triggers medical evaluation. All potential event materials (imaging, records, symptom logs, death certificates) are submitted to an independent CEC for adjudication of event and date, final for analysis.
Time frame
From date of first neoadjuvant dose until the date of first documented events above, whichever came first, assessed up to 36 months2
Overall Survival
Defined as time from neoadjuvant start to death from any cause. Assessed at scheduled visits. Method: Central follow-up unit collects objective death documents from multiple sources. The independent CEC reviews all documents, verifies and adjudicates the exact date of death, which serves as the final basis for OS calculation.
Time frame
From date of first neoadjuvant dose until the date of death from any cause, assessed up to 36 months.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Zhiquan Hu
Lead sponsor
Tongji Hospital
Sponsor institution
Source ClinicalTrials.gov