Neoadjuvant Radiotherapy for High-risk UTUC

NCT06472752 | Not Yet Recruiting DMC

• 1 other identifier: LUXUS 7.0
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators propose to conduct an open-label, single-arm, prospective cohort study to collect and observe high-risk UTUC patients (with clear pathology of urothelial carcinoma and at least one of the following (muscle invasion \[cT2 and above\], high-grade tumour, multifocality, tumour diameter of ≥2cm, with hydronephrosis or regional lymph node metastasis) who undergo neoadjuvant therapy(neoadjuvant radiotherapy with/without drug) + radical nephroureterectomy. The cohort was evaluated by regular follow-up for safety and prognosis during the real-world neoadjuvant treatment period, perioperative period, and long-term postoperative follow-up.

Conditions

Urothelial Carcinoma of the Renal Pelvis and Ureter

Keywords

neoadjuvant radiotherapy; UTUC; prospective cohort; microenviroment; neoadjuvant combined therapy

Outcome Measures

Primary Outcomes (1)

• Local tumor response

  The criteria for evaluating the efficacy of solid tumours classify the evaluation of the lesion into four scenarios: complete response, partial response, stable disease, progression.

  6 months

Secondary Outcomes (2)

• Disease free survival(DFS)

  through study completion, an average of 3 year

• Adverse effects

  Up to 1 year

Other Outcomes (4)

• Overall survival(OS)

  through study completion, an average of 3 year

• Local recurrence free survival (LRFS)

  through study completion, an average of 3 year

• Metastasis free survival (MFS)

  through study completion, an average of 3 year

Study Arms (2)

Neoadjuvant radiotherapy+radical surgery

Patients with high-risk UTUC without distant metastases (which can be accompanied by regional lymph node metastases) were selected to receive short-course neoadjuvant stereotactic radiotherapy (neoadjuvant SBRT, naSBRT) after completion of biopsy and definitive pathological diagnosis, and to undergo radical surgery within 3 months from completion of the last radiotherapy session

Radiation: Neoadjuvant radiotherapy

Neoadjuvant radiotherapy and drug therapy+radical surgery

Patients with high-risk UTUC without distant metastases (which may be accompanied by regional lymph node metastases) were selected to receive a short course of neoadjuvant stereotactic radiotherapy (neoadjuvant SBRT, naSBRT) + drug therapy after completing a biopsy and making a definitive pathological diagnosis, and to undergo a radical surgical procedure within 3 months from the end of the last radiotherapy session (full-length radical nephroureteral resection + cystocele sleeve resection ) treatment. Pharmacological treatment can be chemotherapy/immunotherapy/ADC treatment etc.

Radiation: Neoadjuvant radiotherapy; Combination Product: Neoadjuvant drug therapy

Interventions

Neoadjuvant radiotherapy RADIATION

Patients with a clear pathological diagnosis of high-risk UTUC were treated with a short course of 5 days of naSBRT: radiotherapy irradiation was directed to the primary lesion on the affected side and to the lymphatic drainage area, with a dose of 25 Gy (5 Gy\*5 days).The safety of the neoadjuvant radiotherapy dose and regimen can be evaluated by metrological ramping in the initial 5 patients, with subsequent patients following the optimal dose from ramping.

Neoadjuvant radiotherapy and drug therapy+radical surgery; Neoadjuvant radiotherapy+radical surgery

Neoadjuvant drug therapy COMBINATION_PRODUCT

Patients will concurrently complete at least 2-4 cycles of preoperative neoadjuvant chemotherapy/immunotherapy/ADCs as well.

Neoadjuvant radiotherapy and drug therapy+radical surgery

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

This is an open-label, single-arm, prospective cohort study, and the eligibility criteria for subjects to be included in the study are the same as the inclusion criteria. They will be informed of their informed consent and will voluntarily enrol in the study and sign an informed consent form prior to receiving their first treatment.

You may qualify if:

• ·≥18 years old, no gender limits, diagnosed as high-risk UTUC without existing distant metastasis or other malignancies;
• Completed pathological biopsy with a clear pathological diagnosis : including puncture biopsy, ureteroscopy and urine cytology, at least one of which is clearly diagnosed as uroepithelial carcinoma, which may include no more than 50% or more proportion of squamous, adenoid, sarcomatoid differentiation and other special differentiation types;
• Have the willingness to undergo radical surgical treatment and perioperative adjuvant treatment, have good compliance, and be able to co-operate with the treatment and follow-up plan specified by the clinician;
• Postoperative life expectancy of at least 6 months; ECOG score ≤ 2.

You may not qualify if:

• Distant metastases or other malignant neoplastic diseases combined with other malignant neoplasms in the same period had been detected at the time of surgery, or the present was a progression after palliative resection of previous epithelial carcinoma of the urothelium;
• History of pelvic and abdominal radiotherapy; history of inflammatory bowel disease; history of systemic chemotherapy;
• Pregnant women or breastfeeding women; or women of childbearing potential who are not using reliable contraception;
• The presence of active infections in those with pre-existing or coexisting haemorrhagic disorders
• clinically significant cardiac disease (e.g., hypertension controlled with medications, unstable angina, New York Heart Association (NYHA) class ≥II congestive heart failure, unstable symptomatic arrhythmias, or class ≥II peripheral vascular disease);
• Psychological, familial, and social factors leading to lack of informed consent.

Sponsors & Collaborators

• Peking University First Hospital: lead

Study Sites (1)

Departmeng of Urology, Peking University First Hospital

Beijing, China

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood, urine, and tissue specimens

MeSH Terms

Interventions

Neoadjuvant Therapy

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Department of Urology

Study Record Dates

• First Submitted: June 7, 2024
• First Posted: June 25, 2024
• Study Start: June 30, 2024
• Primary Completion: June 30, 2025
• Study Completion (Estimated): June 30, 2029
• Last Updated: June 25, 2024

Record last verified: 2024-06

Locations

CN (1)