Radiotherapy Combined with Systemic Therapy Versus Systemic Therapy for Oligometastatic UTUCs

Official title

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

Overview

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.

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.

Interventions

• 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.
• 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, carbopla

Primary outcome measures

• PFS [Time frame: 1-year, 3-year and 5-year]

Secondary outcome measures (3)

• OS [Time frame: 1-year, 3-year and 5-year]
• Adverse effect [Time frame: 1 month after the start of treatment until the end of treatment]
• ORR [Time frame: 1-3 months after starting treatment]

Eligibility criteria

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.

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 2 centers

• Departmeng of Urology, Peking University First Hospital — Beijing
• Department of Radiotherapy Oncology, Peking University First Hospital — Beijing

Identifiers

NCT: NCT06652022 · LUXUS5.0

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗