Upper Tract Urothelial Carcinoma
Conditions
Keywords
upper tract urothelial carcinoma, Kidney-Preserving, Disitamab Vedotin, Tislelizumab
Brief summary
This is a prospective, multicentre, single-arm phase II study evaluating a response-adapted kidney-preserving strategy in patients with HER2-positive high-risk upper tract urothelial carcinoma (UTUC). Patients will receive neoadjuvant disitamab vedotin plus tislelizumab, followed by response-adapted local treatment, including kidney-sparing surgery or radical nephroureterectomy based on predefined criteria. The primary objective is to assess whether this multimodal strategy can achieve clinically meaningful oncologic control while preserving renal function, as measured by 1-year kidney-intact event-free survival (KI-EFS). Secondary and exploratory objectives include evaluation of clinical response, survival outcomes, safety, renal function preservation, and longitudinal dynamics of circulating and urinary tumor DNA.
Detailed description
This is a prospective, multicentre, single-arm, phase II clinical trial designed to evaluate the efficacy and safety of a response-adapted kidney-preserving treatment strategy in patients with HER2-positive high-risk upper tract urothelial carcinoma (UTUC). Eligible patients will receive neoadjuvant systemic therapy consisting of disitamab vedotin in combination with tislelizumab administered every 3 weeks for 2-4 cycles. Tumour response will be assessed after two cycles using radiographic evaluation and clinical assessment. Patients demonstrating clinical benefit will proceed to complete induction therapy, followed by comprehensive restaging including imaging, ureteroscopy with biopsy, and urine cytology. Subsequent local treatment will be determined according to a predefined response-adapted algorithm. Patients meeting protocol-specified criteria will undergo kidney-sparing surgery (KSS), including segmental ureterectomy or endoscopic ablation depending on tumour location and anatomical feasibility. Patients not meeting criteria for KSS will undergo radical nephroureterectomy (RNU). The primary objective of the study is to determine whether this multimodal strategy can achieve clinically meaningful oncologic control while preserving renal function in a biomarker-selected population. In addition, longitudinal biospecimen collection will be conducted to evaluate the dynamics of urinary tumor DNA (utDNA) and circulating tumor DNA (ctDNA) as exploratory biomarkers of treatment response and minimal residual disease.
Interventions
In this trial, RC48 was scheduled to be administered at a dose of 2.0 mg/kg every 3 weeks, with the first dose on day 1 of the first cycle. Tislelizumab was administered at a dose of 200 mg every 3 weeks, with the first dose on day 1 of the first 21-day cycle. The drug is diluted with normal saline and administered by intravenous drip for one hour.
Sponsors
RenJi Hospital
West China Hospital
Tianjin Medical University Second Hospital
Peking University First Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is a prospective, open, multiple-center clinical study of renal preservation therapy in high-risk upper urinary tract urothelial carcinoma patients . The study was conducted in accordance with the Good Practice for Quality Control of Clinical Trials for Pharmaceutical Products (GCP). Approximately 20 subjects will be enrolled to evaluate the efficacy and safety of RC48 (2.0 mg/kg intravenously every 3 weeks) combined with Tislelizumab (200mg intravenously every 3 weeks).
Intervention model description
In this trial, RC48 was scheduled to be administered at a dose of 2.0 mg/kg every 3 weeks, with the first dose on day 1 of the first cycle. Tislelizumab was administered at a dose of 200 mg every 3 weeks, with the first dose on day 1 of the first 21-day cycle. The drug is diluted with normal saline and administered by intravenous drip for one hour.
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years at the time of informed consent. * Histologically confirmed upper tract urothelial carcinoma (UTUC) arising from the renal pelvis or ureter, based on ureteroscopic biopsy. * High-risk UTUC, defined by at least one of the following features: Tumour size ≥2 cm; High-grade cytology or biopsy; Radiographic evidence of local invasion (≥cT2); Hydronephrosis; Multifocal disease * Clinical stage cT1-T3, N0-N1, M0, based on radiographic assessment. * N1 disease is permitted only if lymph nodes are considered resectable. * HER2-positive disease, defined as immunohistochemistry (IHC) score of 1+，2+ or 3+ on tumour tissue, assessed according to predefined criteria. * At least one measurable lesion according to RECIST version 1.1. * ECOG performance status of 0-1 * Adequate organ function, including: Hematologic function; Hepatic function; Renal function (no strict upper/lower limit required); * Patients must be considered potential candidates for a kidney-preserving treatment strategy, including: Absolute or relative indication for renal preservation (e.g., solitary kidney, baseline renal insufficiency), or Strong preference for kidney preservation after multidisciplinary discussion * Ability to understand and willingness to sign written informed consent.
Exclusion criteria
* Evidence of distant metastatic disease (M1). * Unresectable or bulky nodal disease (≥N2) not amenable to curative-intent surgery. * Prior systemic therapy for urothelial carcinoma, including:Chemotherapy; Immunotherapy; HER2-targeted therapy. * Prior radical nephroureterectomy for current disease. * Active autoimmune disease requiring systemic treatment within the past 2 years. * Current use of immunosuppressive medication, excluding physiologic doses of corticosteroids. * Uncontrolled intercurrent illness, including but not limited to: Active infection requiring systemic therapy; Uncontrolled cardiovascular disease; Significant pulmonary disease * Known active hepatitis B, hepatitis C, or HIV infection with uncontrolled viral replication. * History of another malignancy within the past 5 years, except: Adequately treated basal cell carcinoma; Squamous cell skin cancer; In situ carcinoma. * Pregnant or breastfeeding women. * Any condition that, in the opinion of the investigator, would interfere with study participation or interpretation of results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Kidney-Intact Event-Free Survival (KI-EFS) at 1 year | From enrollment to 12 months | KI-EFS is defined as the time from study enrollment to the first occurrence of any of the following events: High-risk recurrence of upper tract urothelial carcinoma (local, regional, or distant), defined according to prespecified clinical or radiographic criteria Death from any cause Conversion to radical nephroureterectomy (RNU) for any reason Patients without an event will be censored at the date of last disease assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kidney-Intact Event-Free Survival at 2 years | Up to 24 months | KI-EFS is defined as the time from study enrollment to the first occurrence of any of the following events: High-risk recurrence of upper tract urothelial carcinoma (local, regional, or distant), defined according to prespecified clinical or radiographic criteria Death from any cause Conversion to radical nephroureterectomy (RNU) for any reason Patients without an event will be censored at the date of last disease assessment. |
| Disease-Free Survival (DFS) Renal Function Preservation | Up to 24 months | Time from definitive local treatment (KSS or RNU) to upper tract recurrence or death from any cause. Isolated bladder recurrence will not be counted as an event. |
| Clinical Complete Response (cCR) Rate After Induction Therapy | Immediately after Induction Therapy | Clinical complete response (cCR) was defined as concordant negative findings on cross-sectional imaging, ureteroscopy, urine cytology, and targeted biopsy according to predefined criteria |
| Clinical Complete Response (cCR) Rate After Kidney-Sparing Surgery | 1 month after surgery | Clinical complete response (cCR) was defined as concordant negative findings on cross-sectional imaging, ureteroscopy, urine cytology, and targeted biopsy according to predefined criteria |
| Renal Function Preservation | Up to 12 months | Change in estimated glomerular filtration rate (eGFR) |
| Safety and Tolerability | Up to 90 days post-treatment | Incidence of treatment-related adverse events graded by CTCAE v5.0 |
Countries
China
Contacts
CONTACTjiwei huang
Outcome results
None listed