Toripalimab Combined With Axitinib as Neoadjuvant Therapy in Patients With Non-metastatic Locally Advanced Nonmetastatic Clear Cell Renal Cell Carcinoma

Study Overview
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Brief Summary
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This study is design to prospectively investigate the safety and efficacy of Toripalimab combined with Axitinib in downsizing tumors in patients with nonmetastatic biopsy-proven clear cell renal cell carcinoma. Toripalimab is new antibody that may help activate the immune system by blocking the function of an inhibitory molecule, Programmed cell death-1 (PD-1). This is a single-institution, single-arm phase 2 clinical trial.

Detailed Description
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This study is design to prospectively investigate the safety and efficacy of Toripalimab combined with Axitinib in downsizing tumors in patients with nonmetastatic biopsy-proven clear cell renal cell carcinoma. Toripalimab is new antibody that may help activate the immune system by blocking the function of an inhibitory molecule, Programmed cell death-1 (PD-1). This is a single-institution, single-arm phase 2 clinical trial. Patients will receive axitinib 5 mg bid combined with Toripalimab 3mg/KG q3w for up to 12 wk. Patients then will receive partial or radical nephrectomy after neoadjuvant therapy.

Official Title
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Phase II Study of Toripalimab Combined With Axitinib as Neoadjuvant Therapy in Patients With Non-metastatic Locally Advanced Nonmetastatic Clear Cell Renal Cell Carcinoma

Conditions
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Neoadjuvant Therapy of Non-metastatic Locally Advanced Renal Cell Carcinoma

Intervention / Treatment
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* Drug: Toripalimab
* Drug: Axitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-metastatic biopsy-proven clear cell renal cell carcinoma (T2-T3N0-1M0) Schedule to undergo either partial or radical nephrectomy as part of treatment plan ECOG performance status of 0 or 1 Adequate organ and marrow function defined by study-specified laboratory tests Agree to comply with scheduled visits, treatment plans, lab tests and other study procedures Do not have any other cancers in the 5 yr preceding diagnosis of their renal cancer Exclusion Criteria: Patients who have received other systems for anti-tumor treatment Patients who have previously received targeted or immunotherapy Need for urgent or emergent nephrectomy to relieve symptoms Current use of immunosuppressive agents Pregnant or breastfeeding women History of autoimmune disease or syndrome

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
Intervention Model: Single Group Assignment
Interventional Model Description: Before surgery, patients will receive axitinib 5 mg bid combined with Toripalimab 3mg/KG q3w for up to 12 wk.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neoadjuvant arm<br>Patients will receive axitinib 5 mg bid combined with Toripalimab 3mg/KG q3w for up to 12 wk. | Drug: Toripalimab<br>* 240mg, IV (in the vein) on on day 1 of 3-week, 6-week and 9-week for a total of 3 doses prior to partial nephrectomy or radical nephrectomy<br>* Other names: anti-PD-1 monoclonal antibody;Drug: Axitinib<br>* 5 mg by mouth twice each day for 12 weeks prior to nephrectomy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Tumor Response Rate | Number of patients achieving a complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors | 3 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety assessed by adverse events | Safety as assessed by number of participants experiencing adverse events | through study completion, an average of 4 months | 
| Perioperative complication rate | Perioperativecomplications judged by Clavien-Dindo classification | from perioperative to 90 days after surgery | 
| Quality of Life questionnaire | Quality of Life as assessed by the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) -15 questionnaire | Baseline, 3 weeks, 12 weeks and after surgery | 
| Tumor complexity changing by total R.E.N.A.L. score | R.E.N.A.L. Nephrometry Score) to quantify the anatomical characteristics of renal R.E.N.A.L. score consists of 5 anatomical features, and sum them up. | Baseline, 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neoadjuvant therapy, Toripalimab, axitinib, nephrectomy, partial nephrectomy