CLARA: Somatic and Germline Mechanisms That Impact Renal Cancer Immunotherapy

Hospital das Clínicas de Ribeirão Preto

Status and phase: Active, not recruiting; Phase 2

Conditions: Renal Cancer Metastatic

Treatments: Drug: Nivolumab; Drug: Ipilimumab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05215470

CA209-6E3 (Other Identifier)

U1111-1267-7778 (Registry Identifier)

CLARA

Details and patient eligibility

About

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).

Full 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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

100 participants in 1 patient group

Nivolumab+Ipilimumab

Experimental group

Description:

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.

Treatment:

Drug: Ipilimumab

Drug: Nivolumab