Informations générales (source: ClinicalTrials.gov)
First Line Randomised Study Platform to Optimize Treatment in Patients With Metastatic Renal Cell Carcinoma (CARE1)
Interventional
Phase 3
Gustave Roussy, Cancer Campus, Grand Paris (Voir sur ClinicalTrials)
avril 2024
mai 2032
05 avril 2025
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.
Etablissements
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| AP-HP - Hôpital Bichat | Idir OUZAID, MD, PhD | Contact (sur clinicalTrials) | |||
| AP-HP - Hôpital Henri Mondor-Albert Chenevier | Christophe TOURNIGAND, MD, PhD | Contact (sur clinicalTrials) | |||
| AP-HP - Hôpital Tenon | Ahmed KHALIL, MD | Contact (sur clinicalTrials) | |||
| CLCC INSTITUT GUSTAVE ROUSSY | Laurence ALBIGES, MD, PhD | Contact (sur clinicalTrials) | |||
| HOPITAL FOCH | Raffaele RATTA, MD | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Antoine Lacassagne - 06189 - Nice - France | Delphine BORCHIELLINI, MD | Contact (sur clinicalTrials) | |||
| Centre Eugène Marquis - 35042 - Rennes - France | Brigitte LAGUERRE, MD | Contact (sur clinicalTrials) | |||
| Centre François Baclesse - 14076 - Caen - France | Florence JOLY, MD, PhD | Contact (sur clinicalTrials) | |||
| Centre Georges-François Leclerc - 21079 - Dijon - France | Sylvain LADOIRE, MD, PhD | Contact (sur clinicalTrials) | |||
| Centre Jean Perrin - 63011 - Clermont-Ferrand - France | Hakim MAHAMMEDI, MD | Contact (sur clinicalTrials) | |||
| Centre Léon Bérard - 69008 - Lyon - France | Armelle VINCENEUX, MD | Contact (sur clinicalTrials) | |||
| Centre Oscar Lambret - 59000 - Lille - France | Diane PANNIER, MD | Contact (sur clinicalTrials) | |||
| CH Châlon Sur Saône - 71321 - Chalon Sur Saône - France | Axelle BOUDRANT, MD | Contact (sur clinicalTrials) | |||
| CH de la Côte Basque - 64100 - Bayonne - France | Louis FRANCOIS, MD | Contact (sur clinicalTrials) | |||
| CH de Pau - 64000 - Pau - France | Kévin BOURCIER, MD | Contact (sur clinicalTrials) | |||
| CHD Vendée - 85925 - La Roche-Sur-Yon - France | Charlotte GREILSAMER, MD | Contact (sur clinicalTrials) | |||
| CHU Angers - 49933 - Angers - France | Pierre BIGOT, MD, PhD | Contact (sur clinicalTrials) | |||
| CHU de Bordeaux Hôpital Saint-André - 33000 - Bordeaux - France | Felix LEFORT, MD | Contact (sur clinicalTrials) | |||
| CHU de Nîmes - 30029 - Nîmes - France | Nadine HOUEDE, MD, PhD | Contact (sur clinicalTrials) | |||
| CHU Grenoble - 38043 - Grenoble - France | Mathieu LARAMAS, MD | Contact (sur clinicalTrials) | |||
| CHU Poitiers - 86021 - Poitiers - France | Sheik EMAMBUX, MD | Contact (sur clinicalTrials) | |||
| CHU Saint-Etienne - 42270 - Saint-Etienne - France | Denis MAILLET, MD | Contact (sur clinicalTrials) | |||
| CHU Sud Réunion - 97448 - Saint-Pierre - France | Mohamed KHETTAB, MD | Contact (sur clinicalTrials) | |||
| HIA Bégin - 94160 - Saint-Mandé - France | Carole HELISSEY, MD | Contact (sur clinicalTrials) | |||
| Hôpital Bretonneau - 37044 - Tours - France | Mathilde CANCEL, MD | Contact (sur clinicalTrials) | |||
| Hôpital de la Pitié Salpêtrière - 75013 - Paris - France | Loïc JAFFRELOT, MD | Contact (sur clinicalTrials) | |||
| Hôpital Jean Minjoz - 25030 - Besançon - France | Fabien CALCAGNO, MD | Contact (sur clinicalTrials) | |||
| Hôpital Saint-Louis - 75475 - Paris - France | Clément DUMONT, MD | Contact (sur clinicalTrials) | |||
| Hospices Civils de Lyon - 69310 - Pierre-Bénite - France | Denis MAILLET, MD | Contact (sur clinicalTrials) | |||
| Institut de Cancérologie de Lorraine - 54519 - Vandoeuvre-les-Nancy - France | Lionel GEOFFROIS, MD | Contact (sur clinicalTrials) | |||
| Institut de Cancérologie de l'Ouest - Angers - 49055 - Angers - France | Elouen BOUGHALEM, MD | Contact (sur clinicalTrials) | |||
| Institut de Cancérologie de l'Ouest - Saint Herblain - 44806 - Saint-Herblain - France | Frédéric ROLLAND, MD | Contact (sur clinicalTrials) | |||
| Institut de cancérologie Strasbourg Europe - 67200 - Strasbourg - France | Philippe BARTHELEMY, MD | Contact (sur clinicalTrials) | |||
| Institut Godinot - 51100 - Reims - France | Jean-Christophe EYMARD, MD | Contact (sur clinicalTrials) | |||
| Institut Mutualiste Montsouris - 75674 - Paris - France | Mostefa BENNAMOUN, md | Contact (sur clinicalTrials) | |||
| Institut Paoli-Calmettes - 13009 - Marseille - France | Gwenaelle GRAVIS, MD | Contact (sur clinicalTrials) | |||
| Institut Régional du Cancer de Montpellier - 34298 - Montpellier - France | Diego TOSI, MD, PhD | Contact (sur clinicalTrials) | |||
| Institut Sainte Catherine - 84000 - Avignon - France | Bertrand BILLEMONT, MD | Contact (sur clinicalTrials) | |||
| Oncopole Claudius Regaud - IUCT-Oncopole - 31059 - Toulouse - France | Damien POUESSEL, MD, PhD | Contact (sur clinicalTrials) | |||
| Polyclinique de Limoges - 87000 - Limoges - France | Sabrina FALKOWSKI, MD | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
1. Histologically confirmed metastatic (AJCC Stage IV) renal cell carcinoma with a
clear-cell component.
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.
1. Histologically confirmed metastatic (AJCC Stage IV) renal cell carcinoma with a
clear-cell component.
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.
1. 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.
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.