CLARA: Somatic and Germline Mechanisms That Impact Renal Cancer Immunotherapy

Phase 2

Active, not recruiting

• Conditions: Renal Cancer Metastatic
• Interventions: Drug: Nivolumab; Drug: Ipilimumab

• Registration Number: NCT05215470
• Lead Sponsor: Hospital das Clínicas de Ribeirão Preto

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2022-01-17
• Study Start: 2022-01-18
• Study First Submitted QC: 2022-01-28
• Study First Posted: 2022-01-31
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-01
• Last Update Posted: 2024-07-03
• Primary Completion: 2024-11-30
• Study Completion: 2026-11-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 100

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Nivolumab+Ipilimumab	Nivolumab	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.
Nivolumab+Ipilimumab	Ipilimumab	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.

Primary Outcome Measures

Name	Time	Method
Overall Survival	3 years
Progression-free survival	2 years

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate	2 years

Trial Locations

Locations (1)

Hospital das Clínicas da Faculdade de Medicina de Ribeirao Preto - USP; 🇧🇷 Ribeirão Preto, Sao Paulo, Brazil