Clinical trial · Observational
Multimodal Kidney-Sparing Strategy for High-Risk Upper Tract Urothelial Carcinoma
Evaluating a Kidney-sparing Strategy Combining Endoscopic Surgery, Adjuvant Radiotherapy, and HER2-targeted Antibody-Drug Conjugate in High-risk Upper Tract Urothelial Carcinoma: Study Protocol for a Prospective, Multicenter, Non-randomized Comparative Clinical Trial
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
UTUC is a cancer that develops in the lining of the kidney or ureter. The standard treatment is radical nephroureterectomy, which removes the kidney and ureter. Although this surgery can control the cancer, it permanently reduces kidney function. Endoscopic treatment can serve as a kidney-sparing approach for low-risk UTUC; however, in high-risk patients, the high rate of upper tract local recurrence after endoscopic treatment remains the primary failure pattern. This study aims to evaluate the efficacy and safety of radiotherapy-involved kidney-sparing treatment for UTUC. The main questions this study aims to answer are: Can this multimodal kidney-sparing strategy reduce local recurrence of UTUC compared with endoscopic treatment alone? Participants in the kidney-sparing group will: Undergo endoscopic surgery to remove the tumor; Receive systemic therapy with disitamab vedotin and toripalimab; Receive targeted radiotherapy after surgery. Participants will undergo regular follow-up visits, including imaging examinations and endoscopic evaluations, to monitor for recurrence or disease progression. The results of this study may help determine whether a multimodal kidney-sparing treatment strategy could become a safe and effective option for selected patients with high-risk UTUC.
Conditions
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Upper Tract Urothelial Carcinoma | Renal Pelvis and Ureter Carcinoma | CURATED_BROADER | 0.80 |
| Upper Tract Urothelial Carcinoma Receiving Kidney-sparing Therapy | — | UNRESOLVED | — |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| SBRT | Radiation | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- label
- Kidney-Sparing Multimodal Treatment
- description
- Participants undergo endoscopic tumor ablation or resection using thulium fiber laser techniques. Participants without confirmed complete tumor resection will receive selective hypofractionated radiotherapy approximately one month after surgery.Postoperative systemic therapy consists of disitamab vedotin administered every three weeks for eight cycles combined with toripalimab administered every three weeks for up to one year.
- interventionNames
- Radiation: SBRT
Primary outcomes (2)
- measure
- One-Year Disease-Free Survival
- timeFrame
- 12 months after surgery
- description
- Disease-free survival is defined as the proportion of participants who remain alive without evidence of local recurrence, upper urinary tract recurrence, intravesical recurrence, disease progression, or distant metastasis.
- measure
- One-Year kidney-sparing rate
- timeFrame
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria Participants must meet all of the following criteria: Age 18 years or older Voluntary participation with written informed consent Pathology indicating upper tract urothelial carcinoma with HER2 at least 1+ expression Clinical stage cT1-T2N0M0 based on imaging evaluation Classified as high-risk upper tract urothelial carcinoma according to European Association of Urology (EAU) criteria Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Adequate renal function with split renal function of the affected kidney ≥10 mL/min on renal dynamic scintigraphy Expected life expectancy greater than 24 months Ability and willingness to comply with study procedures and follow-up schedule Exclusion Criteria Participants will be excluded if any of the following conditions are present: Inability to tolerate or refusal of kidney-sparing treatment Evidence of advanced disease (≥T3), lymph node metastasis, or distant metastasis Synchronous bladder urothelial carcinoma or other urological malignancies Previous systemic anticancer therapy, including chemotherapy, targeted therapy, immunotherapy, or antibody-drug conjugates Prior radiotherapy involving the urinary tract or retroperitoneal region Severe uncontrolled comorbidities such as cardiovascular, pulmonary, neurological, psychiatric, or systemic diseases Active severe infections requiring systemic antimicrobial therapy Known immune-related disorders requiring long-term immunosuppressive treatment Pregnancy or breastfeeding Known allergy to investigational drugs used in this study Concurrent participation in another therapeutic clinical trial Indeterminate postoperative pathological diagnosis
References
Publications (3)
- BACKGROUNDSheng X, Zeng G, Zhang C, Zhang Q, Bian J, Niu H, Li J, Shi Y, Yao K, Hu B, Liu Z, Liao H, Yu Z, Jin B, Zhao P, Yang T, Liu X, Qin Y, Xue X, Gou X, Huang J, Gu J, Qi X, Zhang L, Ma G, Liu B, Fang J, Jiang S, He Z, Zhou A, Guo J; RC48-C016 Trial Investigators. Disitamab Vedotin plus Toripalimab in HER2-Expressing Advanced Urothelial Cancer. N Engl J Med. 2025 Dec 11;393(23):2324-2337. doi: 10.1056/NEJMoa2511648. Epub 2025 Oct 19. PMID 41124210
- BACKGROUNDColeman JA, Clark PE, Bixler BR, Buckley DI, Chang SS, Chou R, Hoffman-Censits J, Kulkarni GS, Matin SF, Pierorazio PM, Potretzke AM, Psutka SP, Raman JD, Smith AB, Smith L. Diagnosis and Management of Non-Metastatic Upper Tract Urothelial Carcinoma: AUA/SUO Guideline. J Urol. 2023 Jun;209(6):1071-1081. doi: 10.1097/JU.0000000000003480. Epub 2023 Apr 25. PMID 37096584
- BACKGROUNDMasson-Lecomte A, Birtle A, Pradere B, Capoun O, Comperat E, Dominguez-Escrig JL, Liedberg F, Makaroff L, Mariappan P, Moschini M, Rai BP, van Rhijn BWG, Shariat SF, Smith EJ, Teoh JYC, Soukup V, Wood R, Xylinas EN, Soria F, Seisen T, Gontero P. European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: Summary of the 2025 Update. Eur Urol. 2025 Jun;87(6):697-716. doi: 10.1016/j.eururo.2025.02.023. Epub 2025 Mar 20. PMID 40118741