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CARE1 Pragmatic Clinical Trial

ConditionsMetastatic Kidney CancerMetastatic Kidney Carcinoma
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorGustave Roussy, Cancer Campus, Grand Paris

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Histologically confirmed metastatic (AJCC Stage IV) renal cell carcinoma with a clear-cell component.

Intermediate- or poor-risk mRCC as defined by IMDC classification.

Adult male or female patients (≥ 18 years of age at inclusion).

Karnofsky Performance Status (KPS) ≥70%.

Disqualifiers

Prior systemic anticancer therapy for mRCC including investigational agents. Note: One prior systemic adjuvant therapy is allowed for completely resected RCC and if recurrence occurred at least 6 months after the last dose of adjuvant therapy.

Uncontrolled brain metastases (adequately treated with radiotherapy and/or radiosurgery prior to randomization are eligible). Subjects who are neurologically symptomatic as a result of their CNS metastasis or are receiving systemic corticosteroid treatment (prednisone equivalent > 10 mg/day) at the planned time of randomization are not eligible.

Concomitant oral anti-vitamin K anticoagulation. An exception is the use of LMWH or direct oral anticoagulants (DOAC), if considered safe by investigator assessment.

Pregnant or breastfeeding females.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Nivolumab

    Drug

    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.

  • Ipilimumab

    Drug

    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.

  • Pembrolizumab

    Drug

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

  • Cabozantinib

    Drug

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

  • Axitinib

    Drug

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

  • Lenvatinib

    Drug

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

Treatment groups

1,250 Participants
are divided into 2 treatment groups
Group A: Arm A: ICI - ICI CombinationOther 2 interventions
Group B: Arm B: VEGFR-TKI- ICI arm (axitinib + pembrolizumab)Other 5 interventions

Trial outcomes

Primary outcomes

1

Overall Survival (OS).

From randomization to time of death

Time frame
At end of study, 97 months

Secondary outcomes

1

Progression-free survival according to RECIST 1.1

From randomization to progression, also a primary outcome for PDL1(-) population.

Time frame
At end of study, 97 months
2

Objective Response Rate (ORR) according to RECIST 1.1

ORR (estimand 3) is defined as the percentage of randomised participants (ITT set) who achieve a best response of complete response (CR) or partial response (PR) over the treatment observation period based on Investigators assessments.

Time frame
At end of treatment, 60 months
3

Quality of Life via questionnaire EQ-5D-5L

Patient's response to the Quality of Life questionnaire EQ-5D-5L.

Time frame
Baseline, Month 3, Month 6, Month 9, Month 12
4

Quality of Life via questionnaire NNCCN/FACT Kidney Cancer Symptom Index (NFKSI)

Patient's response to the Quality of Life questionnaire NFKSI19.

Time frame
Baseline, Month 3, Month 6, Month 9, Month 12

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Gustave Roussy, Cancer Campus, Grand Paris

Lead sponsor

European Commission

Collaborator

CRIS Cancer Foundation

Collaborator

National Cancer Institute, France

Collaborator

Rennes University Hospital

Collaborator

University Hospital, Essen

Collaborator

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

Collaborator

The Netherlands Cancer Institute

Collaborator

Servicio Madrileño de Salud, Madrid, Spain

Collaborator

Hospital Universitario 12 de Octubre

Collaborator

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Collaborator

Medical University of Vienna

Collaborator

FAKULTNI NEMOCNICE OLOMOUC

Collaborator

International Kidney Cancer Coalition

Collaborator

Association pour la Recherche sur les Tumeurs du Rein

Collaborator

Resilience

Collaborator

PRIMAA

Collaborator

Queen Mary University of London

Collaborator

Source ClinicalTrials.gov
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