renal cell cancer (patients with locally advanced, non-metastatic renal cell cancer with dominant clear cell pathology) MedDRA version: 21.1 Level: PT Classification code 10067946 Term: Renal cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Yervoy (200mg/40ml)
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Ipilimumab
CAS Number: 477202-00-9
Other descriptive name: MDX010/MDX-CTLA-4
Concentrati
Sponsors
University of Cologne
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - 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 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
Exclusion criteria
Exclusion criteria: - 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •to achieving a >/= 25% remission rate of the primary tumor;Secondary Objective: •to achieving a downstaging to /= 40% •to assess the percentage of treatment-related delay in surgery •to evaluate surgery-related complications as evaluated by Clavien-Dindo classification •to evaluate the progression-free survival rate (PFS) at 1 year postoperatively •to evaluate the duration of response •to evaluate overall survival rate (OS) and disease-free survival (DFS) •to explore quality of life during treatment and follow-up by the use of validated and standardized questionnaires such as FACT-BRM, FKSI-15, NCCN-FKSI-19 •to explore the safety according to the CTCAE classification, version 5.0 ;Primary end point(s): •to achieving a >/=25% remission rate of the primary tumor;Timepoint(s) of evaluation of this end point: The response rate will be calculated by comparing the initial abdominal CT scan with the abdominal imaging study, which is taken prior to surgery on visit 6 in week 11. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • to achieving a downstaging to /=40% • to assess the percentage of treatment-related delay in surgery • to evaluate surgery-related complications as evaluated by Clavien-Dindo classification • to evaluate the progression-free survival rate (PFS) at 1 year postoperatively • to evaluate the duration of response • to evaluate overall survival rate (OS) and disease-free survival (DFS) • to explore quality of life during treatment and follow-up by the use of validated and standardized questionnaires such as FACT-BRM, FKSI-15, NCCN-FKSI-19 • to explore the safety according to the CTCAE classification, version 5.0;Timepoint(s) of evaluation of this end point: - The percentage of change of the diameter of the renal tumor from baseline to week 78-89 (the week before the surgery) based on repetitive CT or MRI scans - Progression-free survival at 1 year postoperatively - Overall survival is defined as the time from initial diagnosis of RCC to death from any noncancer related cause | — |
Countries
Germany
Contacts
Public ContactDepartment of Urology, Uro-Oncology
University Hospital of Cologne
Outcome results
None listed