Neoadjuvant Therapy
Conditions
Keywords
ccRCC, Neoadjuvant therapy, tislelizumab, axitinib
Brief summary
This trial is a single-center clinical trial to evaluate the tumor shrinkage and safety of tislelizumab combined with axitinib in Neoadjuvant therapy of T2-T3N0M0 renal clear cell carcinoma
Detailed description
The goal of the study is to use axitinib combined with tislelizumab in the Neoadjuvant therapy of T2-T3 N0M0 renal clear cell carcinoma to shrink tumors or tumor thrombi, reduce the complexity of surgery, and achieve kidney Partial resection or enucleation of renal tumors instead of kidney Partial resection, or unresectable renal tumors can be changed to resectable and improve the patient's prognosis. The primary endpoint is the tumor shrinkage effect of tislelizumab combined with axitinib in Neoadjuvant therapy of T2-T3N0M0 renal clear cell carcinoma. The secondary end point is * The safety and downgrading rate of tislelizumab combined with axitinib in Neoadjuvant therapy of T2-T3N0M0 renal clear cell carcinoma； * Two-year disease-free survival (DFS) of tislelizumab combined with axitinib in Neoadjuvant therapy of T2-T3N0M0 renal clear cell carcinoma； * Explore biomarkers in tumor tissue and blood that may be related to the efficacy of neoadjuvant therapy and the prognosis of subjects;
Interventions
DRUGtislelizumab combined with axitinib
Subjects received axitinib 5 mg bid, 12 weeks, and tislelizumab 200 mg on the first day of the first week, 4th week, 7th week, and 10th week, and intravenous infusion. With 21 days as a treatment cycle, 4 cycles of treatment, namely 12 weeks. Axitinib was discontinued for 12 weeks after the completion of treatment, and surgery was performed 7 days later.
Sponsors
Hongqian Guo
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-75 years old 2. Imaging is consistent with T2-T3N0M0 renal cell carcinoma 3. Needle pathological biopsy is consistent with renal clear cell carcinoma 4. The subject intends to undergo radical nephrectomy or partial nephrectomy or renal tumor enucleation 5. ECOG 0-1 points 6. Normal hematopoiesis and organ function Hematopoietic function (no blood transfusion or blood products, no use of hematopoietic stimulating factors or other drugs to correct blood cells within 2 weeks before the first trial medication): Absolute neutrophil count (ANC) ≥1.5×109/L; Platelet ≥100×109/L; Hemoglobin ≥9.0g/dL or ≥5.6mmol/L. Kidney function: Serum creatinine ≤ 1.5 times ULN, or serum creatinine\> 1.5×ULN, the creatinine clearance rate is 60 mL/min; liver function: Total bilirubin≤1.5×ULN or total bilirubin\>1.5×ULN but direct bilirubin is normal; AST and ALT≤2.5×ULN; Coagulation: International normalized ratio (INR) or prothrombin time (PT)≤1.5×ULN, and the activated part Thromboplastin time (aPTT)≤1.5×ULN; Left ventricular ejection fraction (LVEF) ≥50% 7. Able to sign informed consent 8. During the entire study period and within 3 months after the last administration, the subjects and their spouses are willing to use efficient contraceptive measures and not to donate sperm; 9. Understand and conduct visits, treatments, laboratory tests, and other research procedures as planned.
Exclusion criteria
1. Previously received anti-tumor immunotherapy, including but not limited to cytokines (IL-2, IFN-α, etc.) and antibody drugs (anti-PD-1, PD-L1 or CTLA-4 antibodies, etc.); 2. Have previously received drug treatments targeting VEGF, VEGFR or mTOR, including but not limited to sunitinib, axitinib, sorafenib, pezopanib, cabotinib, lenvatinib, Bevacizumab or Iverolimus, etc.; 3. Participated in or currently participating in an experimental drug trial within 4 weeks before the first trial drug administration, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study; major surgery within 4 weeks before the first trial drug administration (Judgment by the investigator) or in the recovery period of surgery. 4. Receive Chinese medicine or Chinese patent medicine preparations with anti-tumor indications within 2 weeks before the administration of the first trial. Adrenal cortex hormones (\>10 mg prednisone or equivalent drugs per day) or other immunosuppressive system treatments are required within 2 weeks before the first trial administration; those with \>10 mg prednisone or equivalent drugs per day Inhalers, but those without active autoimmune diseases can participate in this study; 5. The toxicity has not been relieved after previous anti-tumor treatment, that is, it has not subsided to baseline, NCI-CTCAE 5.0 level 0\ 1 (except for hair loss), or the level specified in the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate of tislelizumab combined with axitinib in neoadjuvant treatment of T2-T3N0M0 renal clear cell carcinoma | 7 days before surgery | Objective response rate of tislelizumab combined with axitinib in neoadjuvant treatment of T2-T3N0M0 renal clear cell carcinoma |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The safety of tislelizumab combined with axitinib in neoadjuvant treatment of T2-T3N0M0 renal clear cell carcinoma | Follow-up period | The safety of tislelizumab combined with axitinib in neoadjuvant treatment of T2-T3N0M0 renal clear cell carcinoma |
| Two-year disease-free survival (DFS) of tislelizumab combined with axitinib in neoadjuvant treatment of T2-T3N0M0 renal clear cell carcinoma | Three months to 2 years after surgery | Two-year disease-free survival (DFS) of tislelizumab combined with axitinib in neoadjuvant treatment of T2-T3N0M0 renal clear cell carcinoma |
| Explore biomarkers in tumor tissue and blood that may be related to the efficacy of neoadjuvant therapy and the prognosis of subjects | Three months to 2 years after surgery | The test content covers all exon regions of genes related to the prognosis, medication and development of kidney cancer, including homologous recombination repair (HRR) defect signaling pathways, WNT signal pathway , cell cycle pathway , MAPK signal pathway and chromosome remodeling signaling pathways |
| The downgrading rate of tislelizumab combined with axitinib in neoadjuvant treatment of T2-T3N0M0 renal clear cell carcinoma | Three months to 2 years after surgery | The downgrading rate of tislelizumab combined with axitinib in neoadjuvant treatment of T2-T3N0M0 renal clear cell carcinoma |
Countries
China
Outcome results
None listed