Multimodal Kidney-Sparing Strategy for High-Risk Upper Tract Urothelial Carcinoma

NCT07504939 | Not Yet Recruiting

• 1 other identifier: LUXUS3.1
• Study Type: observational
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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

Upper Tract Urothelial Carcinoma; Upper Tract Urothelial Carcinoma Receiving Kidney-sparing Therapy

Keywords

UTUC; Kidney-Sparing Surgery; Endoscopic Treatment; Disitamab Vedotin; Toripalimab; HER2-Targeted Therapy; Radiotherapy; Multimodal Therapy

Outcome Measures

Primary Outcomes (2)

• One-Year Disease-Free Survival

  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.

  12 months after surgery

• One-Year kidney-sparing rate

  One-Year kidney-sparing rate is defined as the proportion of participants who do not require conversion to radical nephroureterectomy due to disease progression after initial kidney-sparing treatment.

  12 months after surgery

Secondary Outcomes (6)

• Overall Survival

  Up to 5 years

• Progression-Free Survival

  Up to 5 years

• Local Recurrence-Free Survival

  Up to 5 years

• Intravesical Recurrence-Free Survival

  Up to 5 years

• Metastasis-Free Survival

  Up to 5 years

Study Arms (1)

Kidney-Sparing Multimodal Treatment

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.

Radiation: SBRT

Interventions

SBRT RADIATION

Participants without confirmed complete tumor resection will receive selective hypofractionated radiotherapy approximately one month after surgery.

Kidney-Sparing Multimodal Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with clinically histologically confirmed high-risk upper tract urothelial carcinoma who are evaluated and treated at Peking University First Hospital and participating centers will be screened for eligibility. Participants who meet the inclusion criteria and provide informed consent will be enrolled in the kidney-sparing treatment cohort or the radical nephroureterectomy cohort according to clinical decision-making and treatment preference.

You may qualify if:

• Participants must meet all of the following criteria:

You may not qualify if:

• 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

Sponsors & Collaborators

• Peking University First Hospital: lead

Study Sites (1)

Departmeng of Urology, Peking University First Hospital

Beijing, China

Location

Related Publications (3)

• Sheng 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 BACKGROUND

• Coleman 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 BACKGROUND

• Masson-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 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Tumor tissue samples obtained during ureteroscopic biopsy or surgical procedures will be retained for translational research. Peripheral blood samples will also be collected at predefined time points. Biospecimens may be used for molecular analyses, including DNA extraction, biomarker studies, and exploratory translational research such as tumor organoid development and immune profiling.

Central Study Contacts

Xuesong Li, M.D.

CONTACT

+86-15801399116; pineneedle@sina.com

Chenghao Tan, M.D.

CONTACT

+86-83572420; tch1olaf@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chief Physician, Department of Urology, Peking University First Hospital

Study Record Dates

• First Submitted: March 8, 2026
• First Posted: April 1, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): April 1, 2030
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

CN (1)