CLARA: Somatic and Germline Mechanisms That Impact Renal Cancer Immunotherapy

Renal Cancer Metastatic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05215470
• Other study ID #: CLARA
• Secondary ID: U1111-1267-7778C
• Status: Recruiting
• Phase: Phase 2
• Start date: January 18, 2022
• Est. completion date: November 30, 2026

Study information

• Verified date: February 2023
• Source: Hospital das Clínicas de Ribeirão Preto
• Contact: Leandro Machado Colli, MD, PhD
• Phone: 16991744260
• Email: leandroc[@]fmrp.usp.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: November 30, 2026
• Est. primary completion date: November 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Kidney Neoplasms
• Renal Cancer Metastatic

Intervention

Drug:
• Nivolumab
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
• Ipilimumab
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

Locations

Country	Name	City	State
Brazil	Hospital das Clínicas da Faculdade de Medicina de Ribeirao Preto - USP	Ribeirão Preto	Sao Paulo

Sponsors (3)

Lead Sponsor	Collaborator
Hospital das Clínicas de Ribeirão Preto	Bristol-Myers Squibb, Fundação de Amparo à Pesquisa do Estado de São Paulo

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival		3 years
Primary	Progression-free survival		2 years
Secondary	Overall Response Rate		2 years