Radiotherapy Combined with Systemic Therapy Versus Systemic Therapy for Oligometastatic UTUCs

Radiotherapy Combined with Systemic Therapy Versus Systemic Therapy for Oligometastatic Upper Tract Urothelial Carcinoma: a Prospective Randomised Controlled Trial

This study was a prospective, open-label, phase II randomised controlled clinical study, enrolling patients with primary oligometastatic uroepithelial carcinoma, oligometastasis was defined as ≤3 organs, and the number of metastatic lesions and size of metastases were not restricted to be able to satisfy the definition of full-coverage radiotherapy, with the exception of patients with brain metastases and more than 3 liver metastases.

If regional lymph node recurrence was present, all positive regional lymph nodes were collectively referred to as one lesion. Non-regional lymph node metastases were counted as the number of metastases by lymph node subregion.

Patients were divided into two groups according to whether they received radiotherapy or not: 1) systemic therapy group; 2) systemic therapy + radiotherapy group. Systemic drug therapy can be chosen from chemotherapy or immune checkpoint inhibitor therapy, or combination therapy.

Study Overview

• Status: Recruiting
• Conditions: Ureter Cancer; Oligometastatic Disease; Renal Pelvic Carcinoma
• Intervention / Treatment: Drug: Systematic drug treatment; Radiation: Systematic therapy combined with radiotherapy

Detailed Description

This study was a prospective, open-label, phase II randomised controlled clinical study, enrolling patients with primary oligometastatic uroepithelial carcinoma, oligometastasis was defined as ≤3 organs, and the number of metastatic lesions and size of metastases were not restricted to be able to satisfy the definition of full-coverage radiotherapy, with the exception of patients with brain metastases and more than 3 liver metastases.

If regional lymph node recurrence was present, all positive regional lymph nodes were collectively referred to as one lesion. Non-regional lymph node metastases were counted as the number of metastases by lymph node subregion.

Patients were divided into two groups according to whether they received radiotherapy or not: 1) systemic therapy group; 2) systemic therapy + radiotherapy group. Systemic drug therapy can be chosen from chemotherapy or immune checkpoint inhibitor therapy, or combination therapy.

• Study Type: Interventional
• Enrollment (Estimated): 102
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Departmeng of Urology, Peking University First Hospital
    • Contact: Xuesong Li, M.D.; Phone Number: +86-15801399116; Email: pineneedle@sina.com
    • Contact: Chunru Xu, M.D.; Phone Number: +86-17812172086; Email: xcrbdyy@126.com
  • Beijing, China
    • Recruiting
    • Department of Radiotherapy Oncology, Peking University First Hospital
    • Contact: Xiaoying Li, M.D.; Phone Number: +86-13716109164; Email: 13716109164@139.com
    • Contact: Xianshu Gao, M.D.; Phone Number: +86-13716109164; Email: doctorgaoxs@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients with metastatic uroepithelial cancer with histologically confirmed diagnosis (pathologically confirmed primary focus or one of the metastatic foci is sufficient) (metastasis after total cystectomy, metastasis after full-length nephroureteral resection, or metastatic uroepithelial cancer of the pelvic-ureteral bladder at the first diagnosis of inoperable metastatic uroepithelial cancer).
• Oligometastases were defined as ≤3 organs, and the number and size of metastatic lesions were not restricted to the extent that full-coverage radiotherapy could be met. If regional lymph node recurrence was present, all positive regional lymph nodes were collectively referred to as one lesion. Non-regional lymph node metastases are counted as metastases by lymph node subregion.
• Willing and able to provide written informed consent/assent for the trial; age ≥18 years on the date of signing the informed consent form and patient age ≤80 years.
• Expected survival time ≥ 6 months;
• Eastern Collaborative Oncology Group (ECOG) Physical Status (PS) score of 0 to 1;
• Normal major organ function, i.e., the following criteria are met: routine blood tests: a) Haemoglobin ≥ 90 g/L; b) Total bilirubin ≤ 2 x upper limit of normal (ULN); c) Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) ≤ 2.5 x ULN in the absence of liver metastases, and ALT, AST and ALP ≤ 5 x ULN in the presence of liver metastases; d) Creatinine clearance (CrCl) ≥30 mL/min;

Exclusion Criteria:

• Pathological type non-urothelial carcinoma;
• Patients with brain metastases and >3 liver metastases; patients with spinal bone metastases at risk of spinal cord compression; patients with pericardial, pleural or abdominopelvic fluid;
• Patients who are intolerant to or have had a reduction in systemic therapy; patients with tumour progression assessed after 2 cycles of systemic therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Systemic treatment group; The choice of first-line treatment is based on the guidelines, and may include chemotherapy or immune checkpoint inhibitors, or a combination of therapies. For patients who can tolerate cisplatin, chemotherapy is given with the gemcitabine-cisplatin regimen, as follows: gemcitabine 1000mg/m2 d1,8; cisplatin 70 mg/m2, avoiding light, intravenous drip d2; 3 weeks for 1 cycle. For intolerant patients, the gemcitabine-carboplatin regimen is given as follows: gemcitabine 1000 mg/m2 d1,8, IV, carboplatin (4.5×[GFR+25]) mg, IV, d1; 3 weeks as 1 cycle. Immune checkpoint inhibitors and targeted agents may be administered if the patient does not tolerate chemotherapy; either in combination with chemotherapy or directly as first line.	Drug: Systematic drug treatment; The choice of first-line treatment is based on the guidelines, and may include chemotherapy or immune checkpoint inhibitors, or a combination of therapies. For patients who can tolerate cisplatin, chemotherapy is given with the gemcitabine-cisplatin regimen, as follows: gemcitabine 1000mg/m2 d1,8; cisplatin 70 mg/m2, avoiding light, intravenous drip d2; 3 weeks for 1 cycle. For intolerant patients, the gemcitabine-carboplatin regimen is given as follows: gemcitabine 1000 mg/m2 d1,8, IV, carboplatin (4.5×[GFR+25]) mg, IV, d1; 3 weeks as 1 cycle. Immune checkpoint inhibitors and targeted agents may be administered if the patient does not tolerate chemotherapy; either in combination with chemotherapy or directly as first line.
Experimental: Systemic treatment combined with radiotherapy group; For patients with oligometastases, the radiotherapy protocol adopts a full-coverage radiotherapy protocol for metastatic foci, which is used as early as possible during the 2 cycles of systemic treatment for the patients. For retroperitoneal lymph node metastases, the conventional segmental radiotherapy protocol is used, and for isolated metastatic foci, the SBRT radiotherapy is used as much as possible. PETCT was used to determine the location and number of metastatic foci before radiotherapy, and for some patients who could not undergo PETCT, chest, abdominal and pelvic CT, ultrasound of superficial lymph nodes, bone scanning and cranial MRI were used to define the scope of the patient's foci.	Radiation: Systematic therapy combined with radiotherapy; Systematic medical therapy is same as the systematic treatment group. SBRT radiotherapy or conventional fractionated radiotherapy can be used according to the extent and size of the metastatic foci. SBRT radiotherapy is preferred, and a higher dose should be given as far as possible when the normal tissues permit, with a preferred single dose of ≥5Gy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Tumour progression-free survival	1-year, 3-year and 5-year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall survival	1-year, 3-year and 5-year
Adverse effect	Adverse effect related to the therapies	1 month after the start of treatment until the end of treatment
ORR	Oncological response rate	1-3 months after starting treatment

Collaborators and Investigators

• Sponsor: Peking University First Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 30, 2029

Study Registration Dates

• First Submitted: September 12, 2024
• First Submitted That Met QC Criteria: October 20, 2024
• First Posted (Actual): October 22, 2024

Study Record Updates

• Last Update Posted (Actual): October 22, 2024
• Last Update Submitted That Met QC Criteria: October 20, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: radiotherapy; Oligometastatic Disease; Randomized control trial; Upper tract urothelial carcinoma; systematic
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Urologic Neoplasms; Ureteral Diseases; Carcinoma; Ureteral Neoplasms
• Other Study ID Numbers: LUXUS5.0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

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