Neoadjuvant Chemotherapy Before Surgery vs Surgery Alone for UTUC: A Randomized Trial

Phase 2Active Not RecruitingNCT07492225

Changhai Hospital120 enrolled

Overview

This clinical trial aims to compare the effectiveness and safety of two treatment options for patients with high-risk upper tract urothelial carcinoma (UTUC). One group will receive neoadjuvant chemotherapy with gemcitabine and cisplatin followed by surgery (radical nephroureterectomy), while the other group will undergo surgery without chemotherapy. The primary goal is to assess the pathological response to treatment, focusing on how much the tumor shrinks before surgery. The trial will also evaluate the safety of the treatments, overall survival, and recurrence-free survival. This study will help determine whether adding chemotherapy before surgery improves outcomes for patients with high-risk UTUC.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

120

Conditions

Neoadjuvant Therapy Urothelial Carcinoma Ureter Upper Urinary Tract Urothelial Carcinoma

Neoadjuvant Gemcitabine + Cisplatin ChemotherapyDRUG

Patients in the experimental group will receive neoadjuvant chemotherapy with a combination of gemcitabine and cisplatin before undergoing surgery. The chemotherapy regimen consists of: Gemcitabine: 1000 mg/m², administered on Day 1 and Day 8 of each 21-day cycle. Cisplatin: 70 mg/m², administered on Day 2 of each 21-day cycle. This treatment will be repeated for 3 to 4 cycles. The goal of this chemotherapy is to shrink the tumor and improve the chances of a successful surgery. After completing the chemotherapy, patients will undergo radical nephroureterectomy (RNU), a surgery to remove the kidney and ureter affected by cancer, within 6 weeks (+/- 2 weeks) of the last chemotherapy cycle. This approach is designed to evaluate if chemotherapy before surgery can improve pathological response and long-term survival outcomes.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Histologically confirmed high-risk upper tract urothelial carcinoma (UTUC). 2. Clinically non-metastatic UTUC (N≤1, M0) based on imaging (CT/MRI). 3. Planned for radical nephroureterectomy (RNU). 4. ECOG performance status of 0 or 1. 5. Sufficient renal function (GFR ≥45 mL/min) and able to tolerate chemotherapy with cisplatin. 6. Age ≥18 years. 7. Informed consent signed. Exclusion Criteria: 1. Imaging shows ≥N2 disease or metastatic disease (M1). 2. History of invasive or lymph node-positive UTUC or invasive disease in the contralateral upper tract in the last 2 years. 3. Single kidney or contraindication to cisplatin. 4. Currently participating in other interventional clinical trials. 5. History of non-urothelial malignancies (except treated skin basal cell carcinoma or cervical carcinoma in situ). 6. Pregnant or breastfeeding women. 7. Any other medical condition deemed inappropriate by the treating physician.

Outcomes

Primary Outcomes

Pathological Response Rate

Proportion of patients with ypT1N0 or lower after surgery in the neoadjuvant chemotherapy + partial nephrectomy group compared to the direct partial nephrectomy group.

Time frame: 6 weeks after surgery

Secondary Outcomes

Chemotherapy Safety and Tolerability

Incidence, severity, and clinical management of treatment-related adverse events (TRAEs) according to CTCAE v5.0.

Time frame: During chemotherapy and post-surgery follow-up

Overall Survival (OS)

Time from surgery to death from any cause.

Time frame: 24 months after surgery

Cancer-Specific Survival (CSS)

Time from surgery to death due to UTUC.

Time frame: 24 months after surgery

Recurrence-Free Survival (RFS)

Time from surgery to first recurrence of UTUC.

Time frame: 24 months after surgery

Neoadjuvant Chemotherapy Before Surgery vs Surgery Alone for UTUC: A Randomized Trial

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes