CLARA: Somatic and Germline Mechanisms That Impact Renal Cancer Immunotherapy

Study Overview
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Brief Summary
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The study is studying the joint contribution and interactions of germline variants and somatic mutations and their impact on Renal Cell Carcinoma (RCC) development and treatment (immunotherapy).

Detailed Description
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One hundred newly diagnosticated stage IV RCC patients will be recruited in the Ribeirao Preto Medical School. Patients will be treated with immune checkpoint inhibitors (ICI) combination: nivolumab (3 mg/kg of body weight) plus ipilimumab (1 mg/kg) intravenously every three weeks for four doses, followed by nivolumab 480mg every four weeks, until progression, toxicity or complete two years of treatment. Patients will be followed up for the clinical outcome (progression-free survival, best response, and overall survival). Fresh-frozen primary tumor tissue will be collected for somatic genomic characterization. Blood DNA will be genotyped for the identification of common germline variation, as well as ancestry determination.

Official Title
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CLARA: Characterization of Somatic and Germline Mechanisms That Impact the Immunotherapy Treatment and Prognosis of Patients With Renal Cancer

Conditions
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Renal Cancer Metastatic

Intervention / Treatment
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* Drug: Nivolumab
* Drug: Ipilimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Renal cell carcinoma patient: histological confirmed clear cell tumor; First-line metastatic treatment; Stage IV with at least one measured lesion; Fresh-frozen primary tumor tissue available; No previous immunotherapy or tyrosine kinase inhibitor treatment; All International Metastatic RCC Database Consortium (IMDC) Risk Score; Karnofsky Performance Scale (KPS) >=70; >=18 years old. Exclusion Criteria: History of a known or suspected autoimmune disease; Any condition requiring systemic treatment with corticosteroids; Creatinine clearance < 40mL/min; Alanine aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) > 5 x ULN; Pregnant women.

Ages Eligible for Study
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Minimum Age: 18 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nivolumab+Ipilimumab<br>Nivolumab IV 3mg/kg 3/3w + Ipilimumab 1mg/kg 3/3w 4 doses, followed by Nivolumab IV 480mg 4/4w until progression, toxicity, or up to 2 years of use. | Drug: Nivolumab<br>* Nivolumab is called an anti-PD-1 (Programmed Cell Death Ligand 1) or a checkpoint inhibitor and is an antibody (a type of human protein) designed to allow the body's own immune system to destroy tumors<br>* Other names: Opdivo;Drug: Ipilimumab<br>* Ipilimumab is called an anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) and is a type of antibody that works to prevent the body's immune system from stopping to fight a specific cancer<br>* Other names: Yervoy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | 3 years | 
| Progression-free survival |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal Cancer, Nivolumab, Ipilimumab, Immunotherapy, molecular profiling