Trial of neoadjuvant nivolumab plus ipilimumab in patients with localized renal cell carcinoma who are at a high risk of relapse after radical nephrectomy (NEONIRenCa)
- Conditions
- renal cell cancer (patients with locally advanced, non-metastatic renal cell cancer with dominant clear cell pathology)MedDRA version: 21.1Level: PTClassification code 10067946Term: Renal cell carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-005949-33-DE
- Lead Sponsor
- niversity of Cologne
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 40
- Male and female subjects >/= 18 years of age
- Histologically confirmed clear cell carcinoma of the kidney or predominant clear cell features (> 50%) in tumor types of mixed histology
- Localized, high risk clear cell carcinoma of the kidney, cT2 grade (G) 4, cT2b G3, cT3a G3-4, cT3b-4 any grade according to 8th Edition of the 2017 TNM system
- Locoregional lymphadenopathy in the area of the renal hilus and/or the corresponding ipsilateral retroperitoneum are allowed
- Completely resectable primary tumor
- Adequate liver function
- Adequate hematological function:
- Serum creatinine < 1.5x upper limit of normal or > 40 ml/min as calculated by Cockroft-Gault formula
- ECOG performance status 0-1
- estimated life expectancy >/= 12 months
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 25
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15
- Prior systemic treatment with VEGF or VEGF receptor targeted therapy (including, but not limited to, sunitinib, pazopanib, axitinib, tivozanib, and bevacizumab) or prior treatment with an mTOR inhibitor or cytokines
- Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
- Non-clear cell renal carcinoma or predominant non-clear cell elements (> 50%) in tumors of mixed histology
- Extraretroperitoneal and retroperitoneal lymph node metastases and/or systemic metastases
- New York Heart Association Class III/IV heart failure, myocardial infarction within 3 months of trial inclusion; instable angina pectoris or instable arrythmia
- Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (> 10 mg daily prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll
- Any condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
- Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome).
- Severe infections within 4 weeks prior to enrolment in the study including
- History of autoimmune disease
- Administration of a live, attenuated vaccine within 4 weeks prior to enrolment, during the entire period of the application of the drugs ipilimumab and nivolumab as well as for the period of 5 half-lives of the study drugs, or anticipation that such a live, attenuated vaccine will be required during the study.
- Any current SARS-CoV2 infection or proven in the preceeding 3 months
- Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrolment or 5 half-lives of the respective drug/IMP, whichever is longer
- Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrolment
- HIV positive
- Active Hepatitis
- Hypersensitivity to the active substance or to any of the excipients listed in the SmPCs of nivolumab and/or ipilimumab
- Receiving concomitant CYP3A4 inducers or string CYP3A4 inhibitors
- Subject has any concurrent medical condition or disease (e.g. active systemic infection) that is likely to interfere with trial procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this trial.
- Pregnant women and nursing mothers, or women planning to become pregnant while enrolled in this trial or within 3 months after the last dose of nivolumab or ipilimumab
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method