CARE1 Pragmatic Clinical Trial

Sponsor
Gustave Roussy, Cancer Campus, Grand Paris
Study ID
NCT06364631
Phase
PHASE3
Status
Recruiting
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Conditions

  • Metastatic Kidney Cancer
  • Metastatic Kidney Carcinoma

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • 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.

Study Details

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.

Key Dates

Start date
Apr 12, 2024
Status verified
Jan 2025
Primary completion
May 5, 2032
Completion
May 5, 2032

Study Design

Enrollment
1,250 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Other: Arm A: ICI - ICI Combination
    Nivolumab (3 mg/kg infusion, every 3 weeks) x 4 doses + ipilimumab (1 mg/kg infusion, every 3 weeks) x 4 doses. At the end of the 4 injections carried out 21 days apart and in the absence of limiting side effects or progression justifying the cessation of the treatment according to the investigating doctor, maintenance treatment with nivolumab will be continued, at a rate of one injection every 2 weeks at a dose of 240 mg or every 4 weeks at a dose of 480 mg depending on the choice of the investigating doctor. Nivolumab will be administered for a maximum of 2 years. Patients are required to receive all four doses of NIVO+IPI before beginning NIVO monotherapy except for ipilimumab-induced toxicity compatible with nivolumab maintenance.
  • Other: Arm B: VEGFR-TKI- ICI arm (axitinib + pembrolizumab)
    Investigator's choice between: * Axitinib (5 mg oral twice a day) + pembrolizumab (200 mg flat IV every 3 weeks or 400 mg flat IV every 6 weeks). * Cabozantinib (40 mg oral, once a day away from meals) + nivolumab infusion (480 mg flat dose every 4 weeks) * Lenvatinib (20 mg oral, once a day) + pembrolizumab (200 mg flat IV every 3 weeks or 400 mg flat IV every 6 weeks)

Primary Outcome Measure

Overall Survival (OS). [ Time Frame: At end of study, 97 months ]

Central Contacts

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