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

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

The study included 298 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.

Study Overview

• Status: Recruiting
• Conditions: Renal Cell Carcinoma; Neoadjuvant
• Intervention / Treatment: Drug: Axitinib plus Toripalimab; Procedure: nephrectomy

Detailed Description

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 298 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.

• Study Type: Interventional
• Enrollment (Estimated): 298
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Zhiling Zhang, Professor; Phone Number: +86-020-87343860; Email: zhangzhl@sysucc.org.cn

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Cancer Hospital Chinese Academy of Medical Sciences
    • Contact: Sujun Han, Dr
  • Beijing, China
    • Recruiting
    • Peking University First Hospital
    • Contact: Zhisong He, Dr
  • Guangzhou, China
    • Recruiting
    • Sun Yat-sen University Cancer Center
    • Contact: Zhiling Zhang, Dr
  • Hefei, China
    • Recruiting
    • Anhui Provincial Hospital
    • Contact: JUn Xiao, Dr
  • Shanghai, China
    • Recruiting
    • Fudan University Cancer Hospital
    • Contact: Hailiang Zhang, Dr
  • Sichuan, China
    • Recruiting
    • West China Hospital
    • Contact: Hao Zeng, Dr
  • Tianjin, China
    • Recruiting
    • Tianjin Medical University Cancer Institute and Hospital
    • Contact: Yao Xin, Dr
  • Zhengzhou, China
    • Recruiting
    • The First Affiliated Hospital of Zhengzhou Hospital
    • Contact: Xuepei Zhang, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntarily agree to participate in this study and sign the informed consent form;
2. Males or females between 18 years old and 80 years old;
3. Diagnosed as clear cell carcinoma or renal cell carcinoma predominantly composed of clear cell carcinoma through histopathological examination
4. CT or MRI clinical staging is T2G4 or T2 with sarcomatoid differentiation, T3-4, N1;
5. ECOG performance status: 0 or 1 point;
6. Sufficient heart, bone marrow, liver, and kidney functions:

Cardiac function: Cardiac function class 0-2; Blood routine test: WBC≥3.5×10^9/L, absolute neutrophil count ≥1.5×10^9/L, PLT≥75.0×10^9/L, HGB≥80g/L; Liver function: Total bilirubin ≤1.5×upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN; Renal function: GFR ≥ 45 ml/min.

Exclusion Criteria:

1. With distant metastasis
2. Severe liver and renal dysfunction, combined with other serious diseases;
3. Serious cardiovascular disease, including any of the following: myocardial infarction or arteritis or venous thrombosis (such as pulmonary embolism) in the past 1 year;
4. Severe/unstable angina pectoris; uncontrolled hypertension;
5. Class III or IV heart failure by New York Heart Association (NYHA) Functional Classification;
6. Ventricular arrhythmia requiring drug treatment.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neoadjuvant group; Neoadjuvant group will be given the neoadjuvant combination of axitinib plus Toripalimab + nephrectomy	Drug: Axitinib plus Toripalimab; 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.; Other Names: nephrectomy; Procedure: nephrectomy; nephrectomy
Active Comparator: Control group; The control group will be given nephrectomy alone.	Procedure: nephrectomy; nephrectomy

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: ZHOU FANGJIAN
• Collaborators: Pfizer
• Investigators: Principal Investigator: Fangjian Zhou, Professor, Director of Dept. of Urology, Sun Yat-sen University Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: January 11, 2023
• First Submitted That Met QC Criteria: February 12, 2023
• First Posted (Actual): February 22, 2023

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 15, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Urologic Neoplasms; Carcinoma; Kidney Neoplasms; Carcinoma, Renal Cell; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Surgical Procedures, Operative; Azoles; Hydrocarbons; Hydrocarbons, Cyclic; Carboxylic Acids; Hydrocarbons, Aromatic; Amides; Benzene Derivatives; Urologic Surgical Procedures; Urogenital Surgical Procedures; Acids, Carbocyclic; Benzoates; Benzamides; Indazoles; Pyrazoles; Axitinib; toripalimab; Nephrectomy
• Other Study ID Numbers: 2021-FXY-518

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No