CLARA: Somatic and Germline Mechanisms That Impact Renal Cancer Immunotherapy

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Renal Cancer Metastatic
• Intervention / Treatment: Drug: Nivolumab; Drug: Ipilimumab

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 Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo
    • Ribeirão Preto, Sao Paulo, Brazil, 14040-900
      • Hospital Das Clinicas da Faculdade de Medicina de Ribeirão Preto - USP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Nivolumab+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.

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; Other Names: Opdivo; Drug: 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; Other Names: Yervoy

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Response Rate	2 years

Collaborators and Investigators

• Sponsor: Hospital das Clínicas de Ribeirão Preto
• Collaborators: Bristol-Myers Squibb; Fundação de Amparo à Pesquisa do Estado de São Paulo
• Investigators: Principal Investigator: Leandro Machado Colli, MD, PhD, University of Sao Paulo

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2022
• Primary Completion (Estimated): November 30, 2024
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: January 17, 2022
• First Submitted That Met QC Criteria: January 28, 2022
• First Posted (Actual): January 31, 2022

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: July 1, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Nivolumab; Immunotherapy; Ipilimumab; Renal Cancer; molecular profiling
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Neoplasms; Carcinoma, Renal Cell; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Ipilimumab
• Other Study ID Numbers: CLARA; U1111-1267-7778 (Registry Identifier: UTN - WHO); CA209-6E3 (Other Identifier: BMS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The research team is committed to sharing data generated by this project with the research community. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement.
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication.
• IPD Sharing Access Criteria: Requests may be directed to PI.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes