CARE1 Pragmatic Clinical Trial

Summary

Systemic therapy for renal cell carcinoma (RCC) relies on 2 classes of agents: anti-angiogenic targeted therapy (Vascular endothelial growth factor Tyrosine Kinase Inhibitor- VEGFR TKI) and immune checkpoint inhibitor (ICI), targeting either PD1/PDL1 axis or CTLA4. Combination therapy is SOC for clear cell RCC in all guidelines with either ICI-ICI or ICI-VEGFR TKI. However, no head-to-head comparison have been performed between the 2 approaches and patients are treated based on physician decision without clinical /biomarker factors to guide treatment selection. PDL1 staining is, to date, the biomarker that has demonstrated its ability to enrich for overall survival benefit favoring ICI-ICI strategy in PDL1(+) and ICI-VEGFR TKI in PDL1(-) patients.

Study design has been developed to demonstrate that ICI-ICI is superior to ICI-VEGFR TKI in prolonging Overall Survival (OS) for PDL1(+) patients and to demonstrate that ICI-VEGFR TKI is superior to ICI-ICI in prolonging Progression Free Survival (PFS) and OS for PDL1(-) patients.

Conditions

• Metastatic Kidney Cancer
• Metastatic Kidney Carcinoma

Interventions

DRUG

Nivolumab

Briefly, nivolumab is administered as an approximately 30-minute (240mg every 2 weeks) or 60-minute (480mg every 4 weeks) IV infusion. Nivolumab is to be administered first. The nivolumab infusion must be promptly followed by a saline flush to clear the line of nivolumab before starting the ipilimumab infusion.

DRUG

Ipilimumab

The second infusion will always be ipilimumab and will start at least 30 minutes after completion of the nivolumab infusion. Ipilimumab is to be administered as an approximately 30-minute IV infusion. When administered together, nivolumab and ipilimumab will be administered on Day 1 of each 21-day cycle.

DRUG

Pembrolizumab

Pembrolizumab is to be administered as an approximately 30-minute IV infusion.

DRUG

Cabozantinib

Cabozantinib is a medication that is taken orally every day, once a day away from meals at the initial dose of 40 mg/day.

DRUG

Axitinib

Axitinib is a medication that is taken orally every day, 2 times a day continuously, at the starting dose of 5mg x2/day.

DRUG

Lenvatinib

Lenvatinib is a medication that is taken orally every day, once a day at the initial dose of 20mg/day.

Sponsors & Collaborators

• European Commission

  collaborator OTHER

• CRIS Cancer Foundation

  collaborator UNKNOWN

• National Cancer Institute, France

  collaborator OTHER_GOV

• Rennes University Hospital

  collaborator OTHER

• University Hospital, Essen

  collaborator OTHER

• Fundació Privada Institut d'Investigació Oncològica de Vall d'Hebron

  collaborator UNKNOWN

• The Netherlands Cancer Institute

  collaborator OTHER

• Servicio Madrileño de Salud, Madrid, Spain

  collaborator OTHER

• Hospital Universitario 12 de Octubre

  collaborator OTHER

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

  collaborator OTHER

• Medical University of Vienna

  collaborator OTHER

• FAKULTNI NEMOCNICE OLOMOUC

  collaborator UNKNOWN

• International Kidney Cancer Coalition

  collaborator UNKNOWN

• Association pour la Recherche sur les Tumeurs du Rein

  collaborator UNKNOWN

• Resilience

  collaborator INDUSTRY

• PRIMAA

  collaborator UNKNOWN

• Queen Mary University of London

  collaborator OTHER

• Gustave Roussy, Cancer Campus, Grand Paris

  lead OTHER

Principal Investigators

• Laurence ALBIGES, MD, PhD · Gustave Roussy, Cancer Campus, Grand Paris

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-04-12

Primary Completion

2032-05-05

Completion

2032-05-05

Countries

• Austria
• Czechia
• France
• Netherlands

Study Locations