Trial Title:
CARE1 Pragmatic Clinical Trial
NCT ID:
NCT06364631
Condition:
Metastatic Kidney Cancer
Metastatic Kidney Carcinoma
Conditions: Official terms:
Carcinoma
Kidney Neoplasms
Carcinoma, Renal Cell
Pembrolizumab
Nivolumab
Ipilimumab
Lenvatinib
Axitinib
Conditions: Keywords:
METASTATIC KIDNEY CANCER
METASTATIC KIDNEY CARCINOMA
PRAGMATIC CLINICAL TRIAL
PDL1
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
International, multicenter, open-label, randomized, controlled Phase 3 trial - 2 arms (A
and B)
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Nivolumab
Description:
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.
Arm group label:
Arm A: ICI - ICI Combination
Arm group label:
Arm B: VEGFR-TKI- ICI arm (axitinib + pembrolizumab)
Other name:
OPDIVO
Intervention type:
Drug
Intervention name:
Ipilimumab
Description:
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 group label:
Arm A: ICI - ICI Combination
Other name:
YERVOY
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
Pembrolizumab is to be administered as an approximately 30-minute IV infusion.
Arm group label:
Arm B: VEGFR-TKI- ICI arm (axitinib + pembrolizumab)
Other name:
KEYTRUDA
Intervention type:
Drug
Intervention name:
Cabozantinib
Description:
Cabozantinib is a medication that is taken orally every day, once a day away from meals
at the initial dose of 40 mg/day.
Arm group label:
Arm B: VEGFR-TKI- ICI arm (axitinib + pembrolizumab)
Other name:
CABOMETYX
Intervention type:
Drug
Intervention name:
Axitinib
Description:
Axitinib is a medication that is taken orally every day, 2 times a day continuously, at
the starting dose of 5mg x2/day.
Arm group label:
Arm B: VEGFR-TKI- ICI arm (axitinib + pembrolizumab)
Other name:
INLYTA
Intervention type:
Drug
Intervention name:
Lenvatinib
Description:
Lenvatinib is a medication that is taken orally every day, once a day at the initial dose
of 20mg/day.
Arm group label:
Arm B: VEGFR-TKI- ICI arm (axitinib + pembrolizumab)
Other name:
LENVIMA
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.
Detailed description:
In 2020, there were an estimated 431 288 new cases of kidney cancer (Renal Cell
Carcinoma, RCC) globally with 138 611 cases in Europe, leading to 179 368 deaths
worldwide, including 54 054 deaths in Europe (source: IARC/Globocan). To define high
priority topics in academic research and launch dedicated trials, European RCC academic
physicians have gathered into a European initiative - the CARE group.
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'.
Criteria for eligibility:
Criteria:
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.
Exclusion Criteria:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Gustave Roussy
Address:
City:
Villejuif
Zip:
94805
Country:
France
Status:
Recruiting
Contact:
Last name:
Laurence ALBIGES, MD, PhD
Phone:
+33 (0)1 42 11 66 90
Email:
laurence.albiges@gustaveroussy.fr
Start date:
April 12, 2024
Completion date:
May 5, 2032
Lead sponsor:
Agency:
Gustave Roussy, Cancer Campus, Grand Paris
Agency class:
Other
Collaborator:
Agency:
European Commission
Agency class:
Other
Collaborator:
Agency:
CRIS Cancer Foundation
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute, France
Agency class:
Other
Collaborator:
Agency:
Rennes University Hospital
Agency class:
Other
Collaborator:
Agency:
University Hospital, Essen
Agency class:
Other
Collaborator:
Agency:
Fundació Privada Institut d'Investigació Oncològica de Vall d'Hebron
Agency class:
Other
Collaborator:
Agency:
The Netherlands Cancer Institute
Agency class:
Other
Collaborator:
Agency:
Servicio Madrileño de Salud, Madrid, Spain
Agency class:
Other
Collaborator:
Agency:
Hospital Universitario 12 de Octubre
Agency class:
Other
Collaborator:
Agency:
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Agency class:
Other
Collaborator:
Agency:
Medical University of Vienna
Agency class:
Other
Collaborator:
Agency:
FAKULTNI NEMOCNICE OLOMOUC
Agency class:
Other
Collaborator:
Agency:
International Kidney Cancer Coalition
Agency class:
Other
Collaborator:
Agency:
Association pour la Recherche sur les Tumeurs du Rein
Agency class:
Other
Collaborator:
Agency:
Resilience
Agency class:
Industry
Collaborator:
Agency:
PRIMAA
Agency class:
Other
Collaborator:
Agency:
Queen Mary University of London
Agency class:
Other
Source:
Gustave Roussy, Cancer Campus, Grand Paris
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06364631
