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    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2021-005949-33
    Sponsor's Protocol Code Number:Uni-Koeln-4316
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2022-03-02
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedGermany - PEI
    A.2EudraCT number2021-005949-33
    A.3Full title of the trial
    Prospective, single-arm 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)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    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)
    A.4.1Sponsor's protocol code numberUni-Koeln-4316
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorUniversity of Cologne
    B.1.3.4CountryGermany
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportBristol-Myers Squibb
    B.4.2CountryBelgium
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversity Hospital of Cologne
    B.5.2Functional name of contact pointDepartment of Urology, Uro-Oncology
    B.5.3 Address:
    B.5.3.1Street AddressKerpener Straße 62
    B.5.3.2Town/ cityCologne
    B.5.3.3Post code50937
    B.5.3.4CountryGermany
    B.5.4Telephone number+4922147882108
    B.5.5Fax number+4922147882372
    B.5.6E-mailurologie-studienkoordination@uk-koeln.de
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Yervoy (200mg/40ml)
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers Squibb Pharma
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNIpilimumab
    D.3.9.1CAS number 477202-00-9
    D.3.9.3Other descriptive nameMDX010/MDX-CTLA-4
    D.3.9.4EV Substance CodeSUB29397
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Opdivo (100 mg/10 ml)
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers Squibb Pharma
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameNIVOLUMAB - 10ml vial-COMMERCIAL
    D.3.2Product code BMS-936558
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNivolumab
    D.3.9.1CAS number 946414-94-4
    D.3.9.3Other descriptive nameMDX1106, ONO-4538
    D.3.9.4EV Substance CodeSUB122750
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    renal cell cancer (patients with locally advanced, non-metastatic renal cell cancer with dominant clear cell pathology)
    E.1.1.1Medical condition in easily understood language
    non-metastatic renal cell cancer with dominant clear cell pathology
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10067946
    E.1.2Term Renal cell carcinoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    • to achieving a >/= 25% remission rate of the primary tumor
    E.2.2Secondary objectives of the trial
    • to achieving a downstaging to < pT2 in the intention-to-treat population >/= 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
    E.2.3Trial contains a sub-study No
    E.3Principal 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 < 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
    E.4Principal 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
    E.5 End points
    E.5.1Primary end point(s)
    • to achieving a >/=25% remission rate of the primary tumor
    E.5.1.1Timepoint(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.
    E.5.2Secondary end point(s)
    • to achieving a downstaging to < pT2 in the intention-to-treat population >/=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
    E.5.2.1Timepoint(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
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    single-arm
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned4
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of trial in all participating sites is defined as the Database Lock.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months2
    E.8.9.1In the Member State concerned days
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 25
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 15
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state40
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    - subjects will will undergo immediate radical nephrectomy and locoregional lymphadenectomy in case of confirmed local radiographic disease progression and guideline recommended follow-up examinations as a standard of care by local urologists
    - subject will continue with systemic therapy with a regime which needs to be discussed with treating physician in case of systemic progression during the preoperative treatment phase
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2022-05-20
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-05-31
    P. End of Trial
    P.End of Trial StatusOngoing
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