Immunotherapy, Radiation Therapy, Renal Cancer Metastatic, Targeted Therapy
Conditions
Brief summary
This is a prospective, single-center clinical trial designed to evaluate the safety and efficacy of combining stereotactic ablative body radiotherapy (SABR) with the targeted therapy Axitinib and the immunotherapy Toripalimab in patients with recurrent metastatic renal cell carcinoma (RCC). Patients will receive a treatment regimen consisting of Axitinib, Toripalimab, and comprehensive multi-lesion SABR. The primary endpoint is Progression-Free Survival 1 (PFS1), and secondary endpoints include Progression-Free Survival 2 (PFS2), Overall Survival (OS), Local Control (LC), Objective Response Rate (ORR), and Disease Control Rate (DCR). Adverse events will be monitored according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0). The aim of this study is to explore a potentially more effective treatment combination for recurrent metastatic RCC.
Interventions
Radiation dose of 6-10 Gy per fraction, administered in 5 fractions for peripheral lesions. For lesions near organs at risk, partial-SABR will be used. If neither SABR nor partial-SABR is feasible, moderate hypofractionated radiotherapy (MHFRT) with curative doses will be applied.
Toripalimab (intravenous infusion): Dosage: 240 mg intravenously every 3 weeks. Frequency: Administered every 3 weeks for the duration of the study, until progression or unacceptable toxicity occurs or reach 2 years.
Axitinib (oral, tablet): Dosage: 5 mg orally twice daily. Frequency: Daily, for the duration of the study, with continuation during progression or until intolerable side effects occur.
Sponsors
Peking University First Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Histopathologically confirmed renal cell carcinoma with recurrent metastatic lesions confirmed by PET/CT or other systemic imaging. 2. Patients with ≤5 metastatic lesions amenable to complete lesion coverage radiotherapy; or \>5 lesions with at least 3 suitable for radiotherapy as evaluated by the radiotherapy and imaging departments. 3. Age between 18-80 years. 4. Expected survival of ≥12 weeks. 5. Measurable disease based on RECIST Version 1.1. 6. ECOG performance status of 0-2.
Exclusion criteria
1. History of anti-PD-1 or PD-L1 antibody therapy, or radiotherapy. 2. Use of corticosteroids or other immunosuppressants within 14 days before treatment. 3. Autoimmune diseases. 4. History of other malignancies. 5. History of surgery within 28 days before treatment. 6. Allergy to study drug components.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival 1 (PFS1) | From the start of SABR treatment to the first disease progression, up to 2 years. This primary endpoint assesses how long patients survive without disease progression while receiving the combination therapy. | PFS1 is defined as the time from the initiation of stereotactic ablative body radiotherapy (SABR) to the first occurrence of disease progression, as determined by radiological imaging (CT, MRI, or PET/CT) based on RECIST criteria. Disease progression is defined as an increase in the size of target lesions or the appearance of new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From the start of treatment to death or until the end of the study (up to 3 years). This secondary endpoint will help evaluate the overall survival benefits of the combined treatment over a longer period. | Overall survival is defined as the time from the start of treatment (SABR combined with Axitinib and Toripalimab) to death from any cause. |
| Progression-Free Survival 2 (PFS2) | From the start of SABR treatment to the initiation of next-line treatment or death (an average of 3 year) | PFS2 is defined as the time from the start of stereotactic ablative body radiotherapy (SABR) to the need for second-line treatment due to disease progression or clinical deterioration, or to death. This will be measured by assessing the time until the initiation of a next-line treatment regimen or the occurrence of death. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Local Control (LC) | Through study completion, an average of 3 year | Local Control is defined as the percentage of patients who have no evidence of disease progression in the irradiated lesions after treatment |
| Objective Response Rate (ORR) | From the start of treatment to the first radiological evaluation to the best response(an average of 6 months) | Objective Response Rate is defined as the percentage of patients who achieve a complete response (CR) or partial response (PR) |
| Disease Control Rate (DCR) | From the start of treatment to the first disease progression, up to 2 years. | Disease Control Rate is defined as the percentage of patients who achieve a complete response (CR), partial response (PR), or stable disease (SD) |
Countries
China
Outcome results
None listed