Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE3
1250 participants
INTERVENTIONAL
2024-04-12
2032-05-05
Brief Summary
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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.
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Detailed Description
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Systemic therapy for RCC relies on two classes of agents: anti-angiogenic targeted therapy (Vascular endothelial growth factor Tyrosine Kinase Inhibitor- VEGFR TKI) and immune checkpoint inhibitor (ICI), targeting either PD-1/PD-L1 axis or CTLA-4. Combination therapy is standard of care (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 two approaches and patients are treated based on physician decision without clinical or biomarker factors to guide treatment selection. PD-L1 staining is, to date, the biomarker that has demonstrated its ability to enrich for overall survival benefit favoring ICI-ICI strategy in PD-L1(+) and ICI-VEGFR TKI in PD-L1(-) patients.
CARE1 PCT is a prospective randomize phase III study, in first line setting for patients with metastatic clear cell RCC comparing ICI-ICI vs ICI-VEGFR TKI approaches stratified on PD-L1 by local determination. Primary endpoint is overall survival (OS). The trial will enroll 1250 patients over 4 years across eight European countries (France, Spain, Netherlands, Czech Republic, Austria, Germany, Italy, UK) that are part of the CARE consortium. Study Sponsor is Gustave Roussy institute within the GETUG network for France, co-sponsor is developed through main academic networks (eg. SOGUG in Spain) and main institutions across Europe (eg. Cancer Core Europe - CCE). Study design has been develop to demonstrate that ICI-ICI is superior to ICI-VEGFR TKI in prolonging OS for PD-L1(+) patients and that ICI-VEGFR TKI is superior to ICI-ICI in prolonging OS for PD-L1(-) patients. CARE1 PCT has been designed and will be conducted with patient advocacy group representatives (ARTuR and IKCC) input.
CARE1 is an academic phase III study designed to define the optimal combination using a pragmatic routinely implementable biomarker. Therefore, CARE1 will inform practice and has the potential to change treatment guidelines. Taken all together, CARE1 is a unique opportunity to build a large-scale platform to define new biomarker based therapy guidelines as well as to investigate quality of life, patient reported outcome and Health-Economic in front line setting, as well as pathological and blood biobank collection for further translational work. This action is part of the Cancer Mission cluster of projects on 'Diagnosis and treatment'.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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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.
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.
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.
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)
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.
Pembrolizumab
Pembrolizumab is to be administered as an approximately 30-minute IV infusion.
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.
Axitinib
Axitinib is a medication that is taken orally every day, 2 times a day continuously, at the starting dose of 5mg x2/day.
Lenvatinib
Lenvatinib is a medication that is taken orally every day, once a day at the initial dose of 20mg/day.
Interventions
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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.
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.
Pembrolizumab
Pembrolizumab is to be administered as an approximately 30-minute IV infusion.
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.
Axitinib
Axitinib is a medication that is taken orally every day, 2 times a day continuously, at the starting dose of 5mg x2/day.
Lenvatinib
Lenvatinib is a medication that is taken orally every day, once a day at the initial dose of 20mg/day.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Intermediate- or poor-risk mRCC as defined by IMDC classification.
3. Adult male or female patients (≥ 18 years of age at inclusion).
4. Karnofsky Performance Status (KPS) ≥70%.
5. Adequate organ and marrow function, according to investigator assessment and
1. Absolute neutrophil count (ANC) ≥ 1000/μL (≥ 1.5 GI/L)
2. Platelets ≥ 100,000/μL (≥ 100 GI/L)
3. Hemoglobin ≥ 8 g/dL (≥ 80 g/L)
4. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x ULN.
5. Calculated creatinine clearance ≥ 30 mL/min (≥ 0.67 mL/sec) using the CKD- EPI equation
6. Patient should understand, sign, and date the written informed consent form prior to any protocol-specific procedures performed.
7. Patient should be able and willing to comply with study visits and procedures as per protocol
8. Patients must be affiliated to a social security system or beneficiary of the same
9. Female patients must either be of non-reproductive potential or must have a negative serum pregnancy test within 14 days prior to the administration of study drug. Childbearing potential women must have agreed to use one barrier method of contraception, such as condom, plus an additional highly effective method of contraception during treatment on this trial and for up to 5 months after the last dose of study treatment.
10. Fertile men with a female partner of childbearing potential must agree to use one barrier method of contraception, such as condom, during treatment on this trial and for up to 4 months after the last dose of treatment. Their women of childbearing potential partner must agree to use a highly effective method of contraception during the same period.
11. Female subjects of childbearing potential must not be pregnant at screening.
Exclusion Criteria
2. 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.
3. Concomitant oral anti-vitamin K anticoagulation. An exception is the use of LMWH or direct oral anticoagulants (DOAC), if considered safe by investigator assessment.
4. The subject has uncontrolled, significant intercurrent or recent illness such as the following conditions:
a. Cardiovascular disorders:
i. Congestive heart failure (CHF) class III or IV as defined by the New York Heart Association, unstable angina pectoris, myocardial infarction, serious cardiac arrhythmias (e.g., ventricular flutter, ventricular fibrillation, Torsades de pointes).
ii. Uncontrolled hypertension despite optimal antihypertensive treatment.
iii. Stroke, or other symptomatic ischemic event or severe thromboembolic event (e.g., symptomatic pulmonary embolism \[PE\], incidental PE is acceptable if deemed safe by the investigator) within 3 months before randomization.
b. Active GI bleeding or symptomatic Gastrointestinal (GI) tract obstruction
c. Clinically significant bleeding including uncontrolled hematuria, hematemesis, or hemoptysis
d. Autoimmune disease that has been symptomatic or required immunosuppressive systemic treatment within the past two years from the date of randomization.
Note: Patients with a history of Crohn's disease or ulcerative colitis are always excluded
e. Any condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization.
Note: Inhaled, intranasal, intra-articular, or topical steroids are permitted. Adrenal replacement steroid doses \> 10 mg daily prednisone equivalent are permitted. Transient short-term use of systemic corticosteroids for allergic conditions (e.g., contrast allergy) is also allowed.
f. Active infection requiring systemic treatment.
g. Major surgery (e.g., nephrectomy, GI surgery, removal of brain metastasis) within 4 weeks prior to randomization or serious non-healing wound/ulcer/bone fracture.
5. Pregnant or breastfeeding females.
6. Any other active malignancy at time of randomization or diagnosis of another malignancy within 3 years prior to randomization that requires active treatment, except for locally curable cancers that have been apparently cured.
7. Hypersensitivity to any of the active substances or to any of the excipients administered during the study
8. Use of live vaccines within 28 days before randomization
9. Persons deprived of their freedom or under guardianship, or for whom it would be impossible to undergo the medical follow-up required by the trial, for geographic, social or psychological reasons.
18 Years
ALL
No
Sponsors
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European Commission
OTHER
CRIS Cancer Foundation
UNKNOWN
National Cancer Institute, France
OTHER_GOV
Rennes University Hospital
OTHER
University Hospital, Essen
OTHER
Fundació Privada Institut d'Investigació Oncològica de Vall d'Hebron
UNKNOWN
The Netherlands Cancer Institute
OTHER
Servicio Madrileño de Salud, Madrid, Spain
OTHER
Hospital Universitario 12 de Octubre
OTHER
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
OTHER
Medical University of Vienna
OTHER
FAKULTNI NEMOCNICE OLOMOUC
UNKNOWN
International Kidney Cancer Coalition
UNKNOWN
Association pour la Recherche sur les Tumeurs du Rein
UNKNOWN
Resilience
INDUSTRY
PRIMAA
UNKNOWN
Queen Mary University of London
OTHER
Gustave Roussy, Cancer Campus, Grand Paris
OTHER
Responsible Party
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Principal Investigators
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Laurence ALBIGES, MD, PhD
Role: STUDY_CHAIR
Gustave Roussy, Cancer Campus, Grand Paris
Locations
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Medical University of Vienna
Vienna, , Austria
Masarykův onkologický ústav, Masaryk Memorial Cancer Institute (MOU)
Brno, , Czechia
Fakultní nemocnice Hradec Králová, University Hospital Hradec Kralove (FNHK)
Hradec Králové, , Czechia
Fakultní nemocnice Olomouc, University Hospital Olomouc (FNOL)
Olomouc, , Czechia
Fakultní nemocnice v Motole, University Hospital Motol (MOTOL)
Prague, , Czechia
Institut de Cancérologie de l'Ouest - Angers
Angers, , France
CHU Angers
Angers, , France
Institut Sainte Catherine
Avignon, , France
CH de la Côte Basque
Bayonne, , France
Hôpital Jean Minjoz
Besançon, , France
CHU de Bordeaux Hôpital Saint-André
Bordeaux, , France
Centre François Baclesse
Caen, , France
CH Châlon Sur Saône
Chalon-sur-Saône, , France
Centre Jean Perrin
Clermont-Ferrand, , France
Hôpital Henri Mondor
Créteil, , France
Centre Georges-François Leclerc
Dijon, , France
CHU Grenoble
Grenoble, , France
CHD Vendée
La Roche-sur-Yon, , France
Centre Oscar Lambret
Lille, , France
Polyclinique de Limoges
Limoges, , France
Centre Léon Bérard
Lyon, , France
Institut Paoli-Calmettes
Marseille, , France
Institut Régional du Cancer de Montpellier
Montpellier, , France
Centre Antoine Lacassagne
Nice, , France
CHU de Nîmes
Nîmes, , France
Hôpital de la Pitié Salpêtrière
Paris, , France
Hôpital Bichat - Claude Bernard
Paris, , France
Hôpital Tenon
Paris, , France
Hôpital Saint-Louis
Paris, , France
Institut Mutualiste Montsouris
Paris, , France
CH de Pau
Pau, , France
Hospices Civils de Lyon
Pierre-Bénite, , France
CHU Poitiers
Poitiers, , France
Institut Godinot
Reims, , France
Centre Eugène Marquis
Rennes, , France
CHU Saint-Etienne
Saint-Etienne, , France
Institut de Cancérologie de l'Ouest - Saint Herblain
Saint-Herblain, , France
HIA Bégin
Saint-Mandé, , France
CHU Sud Réunion
Saint-Pierre, , France
Institut de cancérologie Strasbourg Europe
Strasbourg, , France
Hôpital Foch
Suresnes, , France
Oncopole Claudius Regaud - IUCT-Oncopole
Toulouse, , France
Hôpital Bretonneau
Tours, , France
Institut de Cancérologie de Lorraine
Vandœuvre-lès-Nancy, , France
Gustave Roussy
Villejuif, , France
Antoni van Leeuwenhoek
Amsterdam, , Netherlands
Countries
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Central Contacts
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Facility Contacts
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Other Identifiers
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2023/3764
Identifier Type: OTHER
Identifier Source: secondary_id
2023-503317-29-00
Identifier Type: -
Identifier Source: org_study_id
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