Neoadjuvant of Axitinib Plus PD-1 to Improve Disease Free Survival of Patients With Renal Cell Carcinoma

Study Overview
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Brief Summary
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The study included 246 RCC patients who were at high risk for recurrence after nephrectomy (T2G3-4 or T3-4 or N1). They were randomly divided to receive axitinib plus PD-1 + surgery or surgery alone at a ratio of 1:1, so as to determine the efficacy of the neoadjuvant combination of axitinib plus PD-1.

Detailed Description
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Given the good results of TKI plus PD-1 in our previous cases and its good effect on advanced RCC, we plan to eliminate tumor micrometastases and improve anti-tumor immunity with the neoadjuvant combination of axitinib plus PD-1, so as to improve patient outcomes. The study included 246 RCC patients who were at high risk for recurrence after nephrectomy (T2G3-4 or T3-4 or N1). They were randomly divided to receive axitinib plus PD-1 + surgery or surgery alone at a ratio of 1:1, so as to determine the efficacy of the neoadjuvant combination of axitinib plus PD-1 and provide evidence-based medical evidence for clinical perioperative treatment of these patients.

Official Title
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A Multicenter Randomized Controlled Clinical Study of Neoadjuvant Combination of Axitinib Plus PD-1 Monoclonal Antibody to Improve Disease Free Survival of Patients With Renal Cell Carcinoma

Conditions
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Renal Cell Carcinoma, Neoadjuvant

Intervention / Treatment
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* Drug: Axitinib plus Toripalimab
* Procedure: nephrectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females between 18 years old and 80 years old; Histopathologically confirmed clear cell carcinoma; Staged as T2G3-4 or T3-T4 or N1 Exclusion Criteria: With distant metastasis Severe liver and renal dysfunction, combined with other serious diseases; Serious cardiovascular disease, including any of the following: myocardial infarction or arteritis or venous thrombosis (such as pulmonary embolism) in the past 1 year; Severe/unstable angina pectoris; uncontrolled hypertension; Class III or IV heart failure by New York Heart Association (NYHA) Functional Classification; Ventricular arrhythmia requiring drug treatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neoadjuvant group<br>Neoadjuvant group will be given the neoadjuvant combination of axitinib plus Toripalimab + nephrectomy | Drug: Axitinib plus Toripalimab<br>* Preoperative treatment with axitinib will be given for 3 months, 5 mg twice daily, orally. Preoperative treatment with Toripalimab will be given for 4 cycles (3 weeks considered one cycle), 240 mg, Q3W.<br>* Other names: nephrectomy;Procedure: nephrectomy<br>* nephrectomy<br>|
| Active Comparator: Control group<br>The control group will be given nephrectomy alone. | Procedure: nephrectomy<br>* nephrectomy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease-free survival (DFS) | To evaluate the efficacy of the neoadjuvant combination of axitinib plus PD-1 in improving the 2-year disease-free survival (DFS) in RCC patients with high-risk for recurrent (T2G3-4 or T3-4, or N1). Disease-free survival (DFS) is defined as time from registration to disease progression or death. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The cancer-specific survival (CSS) | cancer specific survival (CSS) is defined as the period between the date of randomization and the date of death from renal cancer. | 3 years | 
| overall survival (OS) | overall survival (OS) is defined as the period between the date of randomization and the date of death from any cause | 3 years | 
| objective response rate (ORR) | CR and PR rate as assessed by RECIST 1.1 | 3 years | 
| major pathological response (MPR) | MPR (≤10% viable malignant cells per local pathology assessment) | 3 years | 
| adverse event management | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | 3 years |