Neoadjuvant Chemotherapy in High - Risk Upper Tract Urothelial Carcinoma

Single - Center Phase II Clinical Study: Efficacy Evaluation of Neoadjuvant Chemotherapy With Gemcitabine and Cisplatin in High - Risk Upper Tract Urothelial Carcinoma

Upper urinary tract urothelial carcinoma (UTUC) represents a rare yet aggressive malignancy associated with a dismal prognosis. At the point of diagnosis, nearly half of the patients already have invasive disease, and over 70% present with high-grade UTUC. Currently, radical nephroureterectomy (RNU) remains the gold standard of care for high-risk UTUC.

Previous investigations have demonstrated that, in contrast to RNU alone, chemotherapy can effectively reduce the disease recurrence rate and mortality. Moreover, it may confer benefits to patients' overall survival (OS) without impeding the implementation of subsequent definitive surgical treatment. However, the majority of these studies are predominantly retrospective analyses. Although they can, to some degree, reflect the clinical value of neoadjuvant chemotherapy, due to inherent limitations in study design and other confounding factors, there is still a paucity of prospective research evidence for further validation.

Considering that RNU can cause a decline in renal function in patients, and in light of prospective trial outcomes, preoperative neoadjuvant chemotherapy (NAC) has emerged as a preferred treatment option for chemotherapy-eligible UTUC patients.

Study Overview

• Status: Not yet recruiting
• Conditions: NAC; UTUC
• Intervention / Treatment: Drug: Gemcitabine, Cisplatin

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shuxiong Zeng; Phone Number: +86 18930568759; Email: zengshuxiong@126.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Changhai Hospital
      • Contact: Shuxiong Zeng; Phone Number: +86 18930568759; Email: zengshuxiong@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed high - risk upper tract urothelial carcinoma (UTUC). For mixed - type tumors, the histological type should be mainly urothelial carcinoma (≥50%), or urine cytology is positive and imaging diagnosis supports UC.
• Clinically non - metastatic urothelial carcinoma (N≤1 M0), determined by imaging examinations (CT or MRI) of the chest/abdomen/pelvis.
• Patients must plan to undergo radical nephroureterectomy (RNU).
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Patients are potential beneficiaries of cisplatin - based neoadjuvant chemotherapy, with relatively good renal function (GFR≥45ml/min) and able to tolerate drug treatment and surgery.
• Sufficient organ and bone marrow function determined by screening tests.
• Recovered from any reversible toxicity of previous surgery.
• At least 18 years old on the date of registration.
• Informed of the study nature and signed the informed consent form.

Exclusion Criteria:

• Imaging - identified ≥N2 disease or metastatic disease (M1).
• History of invasive or lymph node - positive or metastatic urothelial carcinoma or invasive contralateral upper tract carcinoma within 2 years before registration.
• Patients with only one kidney, or cisplatin intolerant patients.
• Participating in other interventional clinical trials at the time of registration.
• History of non - urothelial malignancies, except those who have been disease - free for at least 1 year as judged by the treating oncologist. History of adequately treated (at the discretion of the treating oncologist) basal cell or squamous cell skin cancer or in - situ cervical cancer is allowed.
• Pregnant or lactating women. Reproductive - potential women/men must agree to use effective contraception methods.
• Any other medical conditions that make the treating doctor consider their participation in the study inappropriate.

Withdrawal/Termination Criteria

• Investigator - determined Withdrawal:
• Tumor recurrence or progression during the clinical trial, and the investigator determines that the subject needs new treatment (such as immediate tumor resection or systemic anti - tumor treatment) and is not suitable to continue the trial. If the investigator judges that the subject can still receive treatment or follow - up for efficacy after tumor recurrence, the subject may not be withdrawn for the time being.
• The subject develops comorbidities, complications, or special physiological changes that are not suitable for continuing the trial.
• Poor compliance of the subject affecting safety and efficacy evaluation:
• The subject does not take medicine or undergo examinations as required.
• The subject uses other drugs or foods that affect safety evaluation.
• The subject has other behaviors that affect the test results.
• Unbearable toxicity, other adverse events, or serious adverse events occur, and the subject is not suitable to continue the trial.
• A grade 3 adverse event related to the study drug occurs and persists for more than 12 days after taking sufficient treatment measures.
• Systemic metastasis or progression is detected during the drug - administration observation period or the surgical period.
• Subject - initiated Withdrawal: Subjects have the right to withdraw from the trial midway according to the informed consent form. If the subject does not withdraw the informed consent but no longer accepts trial drug administration and examinations or is lost to follow - up, it is also regarded as withdrawal. All withdrawn subjects should try to complete the corresponding observation content of the last visit as specified in the protocol. The reason for termination should be noted in the original document. If the subject withdraws due to an adverse event, appropriate treatment should be provided and recorded in the original record.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Neoadjuvant Gemcitabine Plus Cisplatin Chemotherapy Group; Participants receive intravenous gemcitabine (1000 mg/m²) on days 1 and 8, followed by intravenous cisplatin (70 mg/m²) on day 1, every 3 weeks for 4 cycles. This neoadjuvant chemotherapy is administered prior to planned radical nephroureterectomy.

Drug: Gemcitabine, Cisplatin; Gemcitabine (1000mg/m²) and cisplatin (70mg/m²). Gemcitabine is used on the 1st and 8th days of a 21 - day cycle, and cisplatin is used on the 2nd day of the cycle. A total of 3 - 4 cycles are carried out.A dose reduction to 60% of the original dose (adjusted to 0.6 times the initial dose) will be implemented if deemed clinically necessary, contingent upon meeting either of the following criteria: 1) occurrence of grade 3 or higher treatment-related adverse events as per CTCAE v5.0 guidelines, or 2) evidence of renal impairment manifested by a ≥40% decline in glomerular filtration rate (GFR) from baseline measurements.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological response rate（pRR）	defined as postoperative pathology <ypT2N0	At the time of pathological report issuance，approximately within 7-10 business days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response rate (pCR)	defined as postoperative pathology <ypT1N0	At the time of pathological report issuance，approximately within 7-10 business days after surgery
Imaging response rate	defined as tumor size reduction observed on imaging comparisons between pre- and post-chemotherapy assessments, with any decrease classified as a positive response.Tumor size reduction, measured as the change in the longest diameter of the primary tumor via computed tomography (CT) scan according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines.	From the date of the first chemotherapy administration until 2 weeks after the last chemotherapy session, assessed up to 11-14 weeks.
Surgery completion rate	Proportion of patients undergoing surgery	From chemotherapy initiation to surgical resection.Patients should undergo definitive surgery within 6 weeks ( ± 2 weeks) following completion of neoadjuvant chemotherapy
Overall survival (OS)	defined as the duration from the date of surgical resection to the occurrence of death from any cause	From the date of surgery until the date of death or loss to follow-up, with a maximum follow-up period of 2 years.
Cancer - specific survival (CSS)	defined as the time from diagnosis to death directly attributable to the primary cancer or its metastases, excluding mortality from unrelated causes	From the date of diagnosis until the date of death from urothelial carcinoma or last documented follow-up, with a maximum follow-up period of 2 years.
Recurrence - free survival (RFS)	defined as the time from post-surgery to the first documented evidence of local/regional recurrence, distant metastasis, or death from any cause, whichever occurs first	From the date of surgical resection until the date of disease recurrence (radiographically or pathologically confirmed) or death from any cause, whichever occurs first, with a maximum follow-up of 2 years.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
the efficacy by detecting the chromosomal instability (CIN) of blood and urine exfoliated cell DNA	Predicting the efficacy by detecting the chromosomal instability (CIN) of blood and urine exfoliated cell DNA	From the time of collecting the first blood and urine specimens until the time of collecting blood and urine specimens before surgery, assessed up to 15-18 weeks.

Collaborators and Investigators

• Sponsor: Changhai Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 15, 2025
• Primary Completion (Estimated): May 15, 2026
• Study Completion (Estimated): June 15, 2028

Study Registration Dates

• First Submitted: March 16, 2025
• First Submitted That Met QC Criteria: April 13, 2025
• First Posted (Actual): April 15, 2025

Study Record Updates

• Last Update Posted (Actual): April 15, 2025
• Last Update Submitted That Met QC Criteria: April 13, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Transitional Cell; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Gemcitabine
• Other Study ID Numbers: CH-NAC-UTUC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No