Neoadjuvant Chemotherapy in High - Risk Upper Tract Urothelial Carcinoma

ConditionsUTUC NAC

Trial statusNot yet recruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18+

SponsorChanghai Hospital

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Single group

Treatments tested in this trial

Gemcitabine, Cisplatin
Drug
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.

Treatment groups

45 Participants

are divided into 1 treatment group

Group A: Neoadjuvant Gemcitabine Plus Cisplatin Chemotherapy GroupExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

Pathological response rate（pRR）

defined as postoperative pathology \<ypT2N0

Time frame

At the time of pathological report issuance，approximately within 7-10 business days after surgery

Secondary outcomes

Pathological complete response rate (pCR)

defined as postoperative pathology \<ypT1N0

Time frame

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.

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

Proportion of patients undergoing surgery

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)

defined as the duration from the date of surgical resection to the occurrence of death from any cause

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.

Other outcomes

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

Time frame

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.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Changhai Hospital

Lead sponsor

Source ClinicalTrials.gov

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