Radiotherapy Combined with Systemic Therapy Versus Systemic Therapy for Oligometastatic UTUCs

NCT06652022 | Recruiting DMC

• 1 other identifier: LUXUS5.0
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Oligometastatic Disease; Ureter Cancer; Renal Pelvic Carcinoma

Keywords

Oligometastatic Disease; Upper tract urothelial carcinoma; systematic; radiotherapy; Randomized control trial

Outcome Measures

Primary Outcomes (1)

• PFS

  Tumour progression-free survival

  1-year, 3-year and 5-year

Secondary Outcomes (3)

• OS

  1-year, 3-year and 5-year

• Adverse effect

  1 month after the start of treatment until the end of treatment

• ORR

  1-3 months after starting treatment

Study Arms (2)

Systemic treatment group

ACTIVE COMPARATOR

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

Systemic treatment combined with radiotherapy group

EXPERIMENTAL

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

Interventions

Systematic therapy combined with radiotherapy RADIATION

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.

Systemic treatment combined with radiotherapy group

Systematic drug treatment DRUG

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.

Systemic treatment group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking University First Hospital: lead

Study Sites (2)

Departmeng of Urology, Peking University First Hospital

Beijing, China

RECRUITING

Department of Radiotherapy Oncology, Peking University First Hospital

Beijing, China

RECRUITING

MeSH Terms

Conditions

Ureteral Neoplasms

Interventions

Radiotherapy

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Ureteral Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice Director of the Department of Radiation Oncology

Study Record Dates

• First Submitted: September 12, 2024
• First Posted: October 22, 2024
• Study Start: January 1, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 30, 2029
• Last Updated: October 22, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

CN (2)