Systemic Therapy Alone or With Stereotactic Body Radiotherapy for Oligometastatic Kidney Cancer (STROKER Study)

Systemic Therapy Combined With Radiotherapy Versus Systemic Therapy Alone for Oligometastatic Kidney CancER (STROKER): A Multicenter, Randomized Controlled Phase III Trial

This phase III randomized controlled trial evaluates the efficacy of stereotactic body radiation therapy (SBRT) in oligometastatic renal cell carcinoma. The study aims to determine if the addition of SBRT to standard systemic therapy prolong survival compared to the standard systemic therapy alone. In addition, the study will explore the impact of this combined modality therapy on patients' toxicity and quality of life. The researchers will compare SBRT plus standard systemic therapy to standard systemic therapy alone, which is targeted agents and immunotherapy in this case, to determine if SBRT could prolong survival.

PRIMARY OBJECTIVES:

To compare the progression-free survival (PFS) between patients receiving SBRT + standard systemic therapy versus standard systemic therapy alone.

SECONDARY OBJECTIVES:

I. To compare the overall survival (OS) between patients receiving SBRT + standard systemic therapy versus standard systemic therapy alone.

II. To compare the cancer specific survival (CSS) between patients receiving SBRT + standard systemic therapy versus standard systemic therapy alone.

III. To estimate the local control (LC) rate of SBRT. IV. To compare the post-treatment progression-free survival (post-treatment PFS) between patients receiving SBRT + standard systemic therapy versus standard systemic therapy alone.

V. To evaluate treatment-related toxicity after adding SBRT based on patient-reported outcomes and researcher reported adverse events.

VI. To compare the quality of life between patients treated with SBRT or not using EQ-5D-5L, FKSI-DRS and FKSI-19.

OUTLINE: Patients are randomized to either Control arm or SBRT arm.

Control arm: Patients receive standard of care systemic therapy on study. SBRT arm: Patients undergo SBRT to all metastatic sites in addition to standard of care systemic therapy on study.

Patients periodically receive computed tomography (CT), positron emission tomography (PET)/CT, and/or magnetic resonance imaging (MRI) throughout the trial.

Inclusion Criteria:

• Pathologically confirmed diagnosis of renal cell carcinoma of any histology
• Age ≥ 18 years.
• ECOG performance status of 0-2.
• Imaging suggests the presence of distant metastases, with no more than 5 metastatic lesions according to RECIST 1.1 criteria and MDA standards.
• The patient has received local therapy to primary site, including surgery, stereotactic radiotherapy, or ablation.
• The patient has received no more than 2 lines of systemic therapy.
• No significant impairment of major organ function:

Hemoglobin (HB) ≥ 80 g/L Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L Platelets (PLT) ≥ 75 × 10⁹/L Serum total bilirubin ≤ 1.5 × ULN Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN Prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN

Exclusion Criteria:

• Presence of intracranial metastases.
• Target lesions have previously received high-dose irradiation with .
• Target lesions are unsuitable for radiation therapy judged by treating radiation oncologist (e.g., lesions invading the gastrointestinal tract or penetrating the bronchus).
• Uncontrollable metastatic pleural effusion or ascites.
• Presence of other malignancies that have not been cured.
• History of significant psychiatric disorders that impede understanding of informed consent and compliance with the study protocol.
• Presence of other serious illnesses that may pose significant risks or affect radiation therapy.
• Women who are pregnant, breastfeeding, or with plans for childbearing during the study.
• Any other reasons deemed by the investigator to make the subject unsuitable for participation in the study.