Localized or locally advanced renal clear cell carcinoma with intermediate-high risk of recurrence.
Conditions
Interventions
Targeted-Immune Combination Therapy Group:Vorolanib 100 mg QD combined with toripalimab 240 mg Q3W.
Targeted Monotherapy Group:Vorolanib 200 mg QD.
Sponsors
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: 1. Histologically or cytologically confirmed localized or locally advanced renal clear cell carcinoma with intermediate-high recurrence risk. 2. Stratification of participants by recurrence risk: (1) Intermediate-high recurrence risk: 1) T1b-T2, Nuclear grade 4 or sarcomatoid differentiation, N0, M0; 2) pT3, any nuclear grade, N0, M0. (2) High recurrence risk: 1) pT4, any nuclear grade, N0, M0; 2) any pT, any nuclear grade, N+, M0; 3) M1 NED (M1 stage with no tumor residue after resection of oligometastatic lesions within 1 year of nephrectomy or concurrently). 3. tumor samples available for PD-1 testing. 4. Age >=18 years, both genders. 5. Expected survival >=12 months. 6. ECOG performance status 0-1. 7. Normal major organ function, no severe abnormalities or immunodeficiency. Specific lab requirements: Absolute neutrophil count >=1.5×10?/L; Platelets >=100×10?/L; Hemoglobin >=100 g/L; Serum albumin >=30 g/L; Bilirubin =45 mL/min; BUN <=2.5×ULN; TSH <=ULN. If TSH is abnormal, T3 and T4 levels must be normal for inclusion. 8. Able and willing to comply with research and follow-up procedures; 9. Gestational-age men and women must agree to use adequate contraception throughout the study and within 6 months after the end of treatment; 10. Able to understand and willing to sign the consent form.
Exclusion criteria
Exclusion criteria: 1. Patients with advanced or metastatic renal cell carcinoma, non-clear cell renal cell carcinoma, or tumors not completely resected. 2. Those who previously received treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibodies, or other small molecule antiangiogenic drugs targeting T-cell costimulation or checkpoints. 3. Participants who underwent major surgery or chemotherapy within 4 weeks before the first dose, or are more than 12 weeks post-surgery. 4. Individuals allergic to the investigational product. 5. Patients with active bleeding, ulcers, gastrointestinal perforation, obstruction, or uncontrolled hypertension (defined as BP >140/90 mmHg or unstable during screening). 6. Uncontrolled adrenal insufficiency. 7. Congenital or acquired immunodeficiency (e.g., HIV), or active hepatitis B (HBsAg positive, HBV DNA >=2000 IU/ml) or C (HCV antibody positive, viral load >ULN). 8. Active autoimmune disease or history thereof (e.g., autoimmune hepatitis, interstitial pneumonia, uveitis, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyper/hypothyroidism), except vitiligo or childhood asthma in remission without adult intervention. Asthma requiring bronchodilators disqualifies. 9. Symptomatic, visceral metastasis with risk of life-threatening complications (e.g., uncontrolled effusions, lymphangitis, >30% liver involvement). 10. Severe infection within 4 weeks before first dose (requiring IV antibiotics, antifungals, or antivirals), or unexplained fever >38.5°C during screening or before first dose. 11. History of other malignancies within the past five years. 12. Systemic steroid or immunosuppressive therapy within 14 days before first study drug dose. 13. Active tuberculosis. 14. Concurrent use of other investigational or standard anti-tumor drugs. 15. Active infection. 16. Bleeding risk. 17. Cardio-pulmonary or systemic diseases precluding general anesthesia for partial or radical nephrectomy. 18. Pregnant or breastfeeding patients. 19. Other situations that may affect the conduct or assessment of the study, as judged by the investigator (e.g., severe mental illness).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Two - year disease - free survival rate.; | — |
Secondary
| Measure | Time frame |
|---|---|
| Disease - free survival period.;Overall survival period.;The correlation between post - operative MRD - positive status and post - operative recurrence.;Analysis of the efficacy of targeted adjuvant therapy based on MRD and other molecular features.;The lead time of postoperative recurrence detection by tDNA dynamic monitoring over imaging.; | — |
Countries
China
Contacts
Public ContactWen Dong
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Outcome results
None listed