Upper Tract Urothelial Carcinoma
Conditions
Keywords
UTUC, HER2, Disitamab Vedotin, Radiotherapy, Adjuvant Therapy, Cisplatin-Ineligible, Upper Tract Urothelial Carcinoma
Brief summary
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.
Interventions
Disitamab vedotin 2.0 mg/kg (maximum 120 mg) will be administered intravenously every 2 weeks for 12 cycles as adjuvant treatment after radical surgery.
RADIATIONradiotherapy
Adjuvant radiotherapy will be delivered to the regional lymphatic drainage area at 45-50 Gy in 25 fractions over 5 weeks. Suspicious lymph nodes will receive 62.5 Gy in 25 fractions over 5 weeks.
Gemcitabine 1000 mg/m² will be administered on Days 1 and 8 of each 21-day cycle for 4 to 6 cycles as adjuvant treatment after radical surgery.
DRUGcarboplatin
Carboplatin will be administered intravenously on Day 1 of each 21-day cycle at a target AUC of 4.5 to 5 for 4 to 6 cycles as adjuvant treatment after radical surgery.
Sponsors
Peking University First Hospital
RemeGen Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 3-Year Disease-Free Survival | From randomization up to 3 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From randomization up to 3 years | Overall survival (OS) is defined as the time from randomization to death from any cause. |
| Metastasis-Free Survival | From randomization up to 3 years | Metastasis-free survival (MFS) is defined as the time from randomization to first documented distant metastasis or death from any cause, whichever occurs first. |
| Local Recurrence-Free Survival | From randomization up to 3 years | Local recurrence-free survival (LRFS) is defined as the time from randomization to first documented locoregional recurrence in the tumor bed or regional lymph nodes, or death from any cause, whichever occurs first. |
| Bladder Recurrence-Free Survival | From randomization up to 3 years | Bladder recurrence-free survival (BRFS) is defined as the time from randomization to first documented bladder urothelial recurrence or death from any cause, whichever occurs first |
| Incidence of Adverse Events | From first dose through 30 days after completion of study treatment and up to 3 years for follow-up | Safety will be evaluated based on the incidence, type, severity, and attribution of adverse events during study treatment and follow-up. |
| Patient-Reported Quality of Life | Baseline through 3 years | Patient-reported quality of life will be assessed using validated quality-of-life questionnaires during treatment and follow-up. |
Countries
China
Contacts
CONTACTXuesong Li, Dr.
CONTACTZihao Tao, Dr.
Outcome results
None listed