Kidney Cancer Metastatic, Renal Cell Carcinoma (Kidney Cancer), Renal Cell Carcinoma Metastatic
Conditions
Keywords
radiotherapy, SBRT, SABR, oligometastatic, oligometastasis
Brief summary
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.
Detailed description
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.
Interventions
RADIATIONStereotactic body radiotherapy (SBRT)
The preferred treatment plan is SBRT with a fraction dose ≥7 Gy. The prescription dose should ensure a BED of no less than 115. Radiotherapy is usually delivered daily, every other day, or other interval decided by treating radiation oncologist.
DRUGaxitinib ± immune checkpoint inhibitors (ICIs), lenvatinib ± ICIs, cabozantinib ± ICIs, sunitinib and pazopanib
Standard systemic therapy are targeted agents or their combination with immunotherapy recommended by guidelines. This may include axitinib ± immune checkpoint inhibitors (ICIs), lenvatinib ± ICIs, cabozantinib ± ICIs, sunitinib and pazopanib, etc.
Sponsors
Sun Yat-sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival | From enrollment to disease progression, up to 5 years | the time from randomization to the first occurrence of tumor progression or death. If no progression occurs, PFS is measured up to the date of the last follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post-treatment progression free survival | From the initiation of systemic treatment to disease progression, up to 5 years | The time from the initiation of systemic treatment for metastasis to the first occurrence of tumor progression or death after enrollment. If no progression occurs, it is measured up to the date of the last follow-up. |
| Progression-free survival 2 | From the initiation of systemic treatment to disease progression, up to 5 years | Defined as the time from randomization to progression on the next-line treatment or death from any cause. |
| Overall survival | From enrollment to death from any cause, up to 5 years | The time from randomization to death from any cause. If no death occurs, OS is measured up to the date of the last follow-up. |
| Cancer specific survival | From enrollment to death from cancer, up to 5 years | the interval from randomization to death caused by renal cancer. If no death occurs, it is measured up to the date of the last follow-up. |
| Local control rate | From enrollment to in-field progression, up to 5 years | The interval from randomization to progression of each SBRT treatment lesion. If no progression occurs, it is measured up to the date of the last follow-up. |
| Patient-Reported Adverse Events | Up to 2 years | Adverse events will be selected from the patient-reported outcomes (PRO) scoring system developed by the National Cancer Institute (NCI) for toxic events (specifically, the NCI PRO-CTCAE™ ITEMS Chinese version). These items will be provided to patients, who will self-assess and report any adverse events experienced during each treatment cycle. |
| Health-related quality of life by EQ-5D-5L | Up to 2 years | The overall quality of life will be evaluated using the European Quality of Life 5-Dimension 5-Level (EQ-5D-5L) scale. |
| Health-related quality of life by FSKI | Up to 2 years | For assessing quality of life related to advanced kidney cancer, the Functional Assessment of Cancer Therapy - Kidney Cancer Symptom Index (FKSI), developed by the American Outcomes Research and Education Center, will be utilized, which includes both the FKSI-DRS and FKSI-19 scales. |
| Incidence of Adverse Events | Up to 2 years | Adverse events need to be grouped and analyzed based on treatment-related events, including all grades and grades 3-4 events. Adverse events are assessed by investigators according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. |
Countries
China
Contacts
Primary ContactLiru He, PhD
Backup ContactFangjian Zhou, PhD
Outcome results
None listed