Neoadjuvant Chemotherapy in High - Risk Upper Tract Urothelial Carcinoma

Official title

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

Overview

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.

Interventions

• 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, o

Primary outcome measures

• Pathological response rate（pRR） [Time frame: At the time of pathological report issuance，approximately within 7-10 business days after surgery]

Secondary outcome measures (6)

• Pathological complete response rate (pCR) [Time frame: At the time of pathological report issuance，approximately within 7-10 business days after surgery]
• Imaging response rate [Time frame: 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 [Time frame: From chemotherapy initiation to surgical resection.Patients should undergo definitive surgery within 6 weeks ( ± 2 weeks) following completion of neoadjuvant chemotherapy]
• Overall survival (OS) [Time frame: 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) [Time frame: 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) [Time frame: 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.]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Changhai hospital — Shanghai

Identifiers

NCT: NCT06927128 · CH-NAC-UTUC

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗