Disitamab Vedotin Plus Radiotherapy for Adjuvant Treatment of HER2-Expressing Cisplatin-Ineligible Upper Tract Urothelial Carcinoma

Phase 2Not Yet RecruitingNCT07498907

Peking University First Hospital192 enrolled

Overview

This randomized, open-label, multicenter phase II study is designed to compare disitamab vedotin plus radiotherapy with gemcitabine plus carboplatin as adjuvant treatment in patients with HER2-expressing upper tract urothelial carcinoma after radical nephroureterectomy (RNU). Eligible patients must have postoperative pathologic stage pT3-pT4N0M0 or pTanyN+M0, HER2 expression defined as immunohistochemistry (IHC) 1+, 2+, or 3+, and be cisplatin-ineligible. Patients will be randomized in a 2:1 ratio to receive disitamab vedotin plus radiotherapy or gemcitabine plus carboplatin. The primary endpoint is 3-year disease-free survival. Secondary endpoints include overall survival, metastasis-free survival, local recurrence-free survival, bladder recurrence-free survival, incidence of adverse events, and patient-reported quality of life.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

192

Conditions

Upper Tract Urothelial Carcinoma

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Aged 18 years or older. * Histologically confirmed upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). * Postoperative pathologic stage pT3-pT4N0M0 or pTanyN+M0. * HER2 expression confirmed by immunohistochemistry (IHC 1+, 2+, or 3+). * Cisplatin-ineligible, defined as meeting at least one of the following criteria: ECOG performance status 2; creatinine clearance \<60 mL/min; CTCAE grade 2 or higher hearing loss; CTCAE grade 2 or higher peripheral neuropathy; or New York Heart Association (NYHA) class III heart failure. * Adequate organ function. * Expected survival of at least 6 months. Exclusion Criteria: * History of other active malignancies, except for adequately treated malignancies with low risk of recurrence. * Prior systemic antitumor therapy before study treatment, or unresolved toxicities from prior therapy. * Known hypersensitivity to disitamab vedotin, related agents, or any component of the study treatment. * Severe active infection. * Not adequately recovered from surgery. * Pregnant or breastfeeding women. * Any other condition that, in the investigator's judgment, makes the patient unsuitable for participation in the study.

Outcomes

Primary Outcomes

3-Year Disease-Free Survival

Disease-free survival (DFS) is defined as the time from randomization to first recurrence in the tumor bed, first metastasis, or death from any cause, whichever occurs first.