A Comparative Study of Neoadjuvant Chemotherapy Versus Upfront Radical Surgery for Upper Tract Urothelial Carcinoma

NCT ID: NCT07155044

Last Updated: 2025-09-04

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 120 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-05-15
• Study Completion Date: 2029-05-15

Brief Summary

This is a single-center, open-label, non-randomized controlled trial comparing the efficacy and safety of neoadjuvant chemotherapy (NAC) followed by radical surgery versus upfront radical surgery alone in patients with high-risk, non-metastatic upper tract urothelial carcinoma (UTUC).

The study aims to answer the following key questions:

Does NAC improve pathologic response rates (defined as downstaging to <ypT2N0) compared to immediate surgery? What is the rate of pathologic complete response (pCR; ypT0N0) in the NAC group? How do the two treatment strategies compare in terms of overall survival, cancer-specific survival, and recurrence-free survival? What is the safety and tolerability profile of NAC using gemcitabine and cisplatin in this patient population? Eligible participants will be assigned to either the NAC-plus-surgery group or the surgery-only group based on clinical evaluation and patient preference. The study will also explore potential biomarkers (e.g., chromosomal instability in liquid biopsies) for predicting treatment response.

Key Eligibility Criteria:

Adults with histologically confirmed high-risk UTUC Clinical stage ≤N1 M0 Adequate renal function (GFR ≥45 mL/min) and ECOG performance status 0-1

Primary Outcome:

Pathologic response rate (proportion of patients with <ypT2N0)

Conditions

UTUC; UC (Urothelial Cancer)

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

NAC+RNU

Intervention: Participants in this cohort will receive 3-4 cycles of neoadjuvant chemotherapy (NAC) with the gemcitabine and cisplatin (GC) regimen prior to undergoing definitive surgery. Gemcitabine (1000 mg/m²) will be administered on Day 1 and Day 8, and cisplatin (70 mg/m²) will be administered on Day 2 of each 21-day cycle.

Surgical Intervention: Following the completion of NAC, patients will undergo a radical nephroureterectomy (RNU) with bladder cuff excision. The procedure will be performed via robot-assisted (Da Vinci), laparoscopic, or open approach, based on surgical discretion. Surgery must be performed within 6 weeks (±2 weeks) after the last dose of chemotherapy.

Objective: The primary objective for this cohort is to evaluate the efficacy of NAC in inducing pathological downstaging (defined as achieving pathological stage <ypT2N0 at surgery) and to assess the pathological complete response (pCR) rate (ypT0N0).

NAC

Intervention Type: DRUG

Participants in NAC+RNU cohort will receive 3-4 cycles of neoadjuvant chemotherapy (NAC) with the gemcitabine and cisplatin (GC) regimen prior to undergoing definitive surgery. Gemcitabine (1000 mg/m²) will be administered on Day 1 and Day 8, and cisplatin (70 mg/m²) will be administered on Day 2 of each 21-day cycle.

RNU

Intervention: Participants in this cohort will proceed directly to radical nephroureterectomy (RNU) with bladder cuff excision without receiving any prior systemic chemotherapy. The surgery will be scheduled as soon as feasibly possible after enrollment and confirmation of eligibility.

Surgical Intervention: The surgical approach (robot-assisted, laparoscopic, or open) will be identical to that offered in Cohort A, chosen at the surgeon's discretion based on standard clinical practice.

Objective: This cohort serves as the control group to provide a contemporary benchmark for standard-of-care outcomes. The objective is to establish the baseline rates of pathological stage distribution, survival, and recurrence without the influence of NAC.

No interventions assigned to this group

Interventions

NAC

Participants in NAC+RNU cohort will receive 3-4 cycles of neoadjuvant chemotherapy (NAC) with the gemcitabine and cisplatin (GC) regimen prior to undergoing definitive surgery. Gemcitabine (1000 mg/m²) will be administered on Day 1 and Day 8, and cisplatin (70 mg/m²) will be administered on Day 2 of each 21-day cycle.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed upper tract urothelial carcinoma (UTUC). For mixed histology, urothelial carcinoma must be the predominant component (≥50%).
• Clinically non-metastatic disease (cN≤1, M0) as determined by cross-sectional imaging (CT or MRI of chest/abdomen/pelvis).
• Planned treatment with radical nephroureterectomy (RNU).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate renal function, defined as glomerular filtration rate (GFR) ≥ 45 mL/min, making the patient a potential candidate for cisplatin-based neoadjuvant chemotherapy.
• Adequate organ and bone marrow function as determined by standard screening tests.
• Recovery from all reversible toxicities of any prior surgery.
• Age ≥ 18 years at the time of enrollment.
• Ability to understand the study and provide signed informed consent.

Exclusion Criteria

• Radiographic evidence of ≥cN2 lymph node disease or distant metastases (M1).
• History of invasive, lymph node-positive, or metastatic urothelial carcinoma within 2 years prior to enrollment, or history of invasive contralateral UTUC.
• Presence of only a solitary kidney or cisplatin ineligibility.
• Concurrent participation in another interventional clinical trial at the time of enrollment.
• History of a non-urothelial malignant tumor unless the patient has been disease-free for at least 1 year (exceptions include adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix).
• Pregnancy or lactation. Women and men of reproductive potential must agree to use effective contraception.
• Any other medical condition, comorbidity, or psychiatric illness that, in the investigator's judgment, would make the patient an unsuitable candidate for the study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Changhai Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Changhai Hospital

Shanghai, Shanghai Municipality, China

Countries

China

Other Identifiers

CH-NAC+UTUC

Identifier Type: -

Identifier Source: org_study_id