CARE1: FIRST LINE RANDOMISED STUDY PLATFORM TO OPTIMIZE TREATMENT IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMA

Trial details

Who runs it

Institut Gustave Roussy

Trial code

EU 2023-503317-29-00

Record updated

2026. szeptember 28.

Original description

To compare the efficacy of immune checkpoint inhibitor combination (ICI-ICI) with nivolumab-ipilimumab (NIVO-IPI) versus ICI-VEGFR TKI combination in IMDC intermediate and poor risk patients with previously untreated mRCC based on PDL1 stratification. The efficacy will be compared in terms of overall survival for the PDL1(+) population and in terms of progression-free survival and overall survival (co-primary endpoints) for the PDL1(-) population.Read full original descriptionShow less

To compare the efficacy of immune checkpoint inhibitor combination (ICI-ICI) with nivolumab-ipilimumab (NIVO-IPI) versus ICI-VEGFR TKI combination in IMDC intermediate and poor risk patients with previously untreated mRCC based on PDL1 stratification. The efficacy will be compared in terms of overall survival for the PDL1(+) population and in terms of progression-free survival and overall survival (co-primary endpoints) for the PDL1(-) population.

Inclusion: Histologically confirmed metastatic (AJCC Stage IV) renal cell carcinoma with a clear-cell component; Fertile men with a female partner of childbearing potential must agree to use malecondom plus spermicide. Also, it is recommended their women of childbearing potentialpartner use a highly effective method of contraception; Female subjects of childbearing potential must not be pregnant at screening; 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%; Adequate organ and marrow function, according to investigator assessment and a.Absolute neutrophil count (ANC) ≥ 1000/μL (≥ 1.5 GI/L) b.Platelets ≥ 100,000/μL (≥ 100 GI/L) c.Hemoglobin ≥ 8 g/dL (≥ 80 g/L) d.Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 xULN. e.Calculated creatinine clearance ≥ 30 mL/min (≥ 0.67 mL/sec) using the CKD-EPI equation; Patient should understand, sign, and date the written informed consent form prior to anyprotocol-specific procedures performed; Patient should be able and willing to comply with study visits and procedures as per protocol; Patients must be affiliated to a social security system or beneficiary of the same; Female patients must either be of non-reproductive potential or must have a negativeserum pregnancy test within 14 days prior to the administration of study drug.Childbearing potential women must have agreed to use at least one highly effectivecontraceptive method during treatment on this trial and for up to 6 months after the lastdose of study treatment.

Exclusion: Prior systemic anticancer therapy for mRCC including investigational agents. Note: One prior systemic adjuvant therapy is allowed for completely resected RCC and ifrecurrence occurred at least 6 months after the last dose of adjuvant therapy; Uncontrolled brain metastases (adequately treated with radiotherapy and/orradiosurgery prior to randomization are eligible). Subjects who are neurologicallysymptomatic as a result of their CNS metastasis or are receiving systemic corticosteroidtreatment (prednisone equivalent > 10 mg/day) at the planned time of randomizationare not eligible; Concomitant oral anti-vitamin K anticoagulation. An exception is the use of LMWH ordirect oral anticoagulants (DOAC), if considered safe by investigator assessment; The subject has uncontrolled, significant intercurrent or recent illness such as thefollowing conditions: a.Cardiovascular i.Congestive heart failure (CHF) class III or IV as defined by the NewYork Heart Association, unstable angina pectoris, myocardialinfarction, 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 thromboembolicevent (e.g., symptomatic pulmonary embolism [PE], incidental PE isacceptable if deemed safe by the investigator) within 3 months beforerandomization. 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 requiredimmunosuppressive systemic treatment within the past two years from the dateof 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 mgdaily prednisone equivalent) or other immunosuppressive medications within14 days of randomization. Note: Inhaled, intranasal, intra-articular, or topical steroids are permitted.Adrenal replacement steroid doses > 10 mg daily prednisone equivalent arepermitted. Transient short-term use of systemic corticosteroids for allergicconditions (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/bonefracture. disorders; Any other active malignancy at time of randomization or diagnosis of anothermalignancy within 3 years prior to randomization that requires active treatment, exceptfor locally curable cancers that have been apparently cured; Pregnant or breastfeeding females; 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, socialor psychological reasons.

EU CTIS 2023-503317-29-00