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The European Union Clinical Trials Register   allows you to search for protocol and results information on:
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    The EU Clinical Trials Register currently displays   43801   clinical trials with a EudraCT protocol, of which   7272   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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    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
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    EudraCT Number:2016-004787-20
    Sponsor's Protocol Code Number:MED3-201601
    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:2017-07-05
    Trial results
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    A. Protocol Information
    A.1Member State ConcernedGermany - PEI
    A.2EudraCT number2016-004787-20
    A.3Full title of the trial
    An Open Label, Randomized Phase 2 Clinical Trial of Nivolumab investigating Effiacy and safety of Nivolumab given once prior to, concurrent to the radiotherapy (RT) and as maintenance therapy over 12 months in patients with advanced resectable HNSCC after surgery (NadiHN)
    Offene, randomisierte Phase-II-Studie bei Patienten mit resektablem fortgeschrittenem Plattenepithelcarcinom des Kopf-Hals-Bereichs (Stadium III ohne Risikofaktor), die die Effektivität und Sicherheit von Nivolumab in Kombination mit einer adjuvanten Strahlentherapie versus der Effektivität einer alleinigen Strahlentherapie untersucht
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    An Open Label, Randomized Phase 2 Clinical Trial of Nivolumab investigating Effiacy and safety of Nivolumab given once prior to, concurrent to the radiotherapy (RT) and as maintenance therapy over 12 months in patients with advanced resectable HNSCC after surgery (NadiHN)
    Offene, randomisierte Phase-II-Studie bei Patienten mit operablem fortgeschrittenem Plattenepithelcarcinom des Kopf-Hals-Bereichs (Stadium III ohne Risikofaktor), die die Verträglichkeit und Wirksamkei von Nivolumab in Kombination mit einer adjuvanten Strahlentherapie mit der Wirksamkeit einer alleinigen Strahlentherapie vergleicht.
    A.3.2Name or abbreviated title of the trial where available
    A.4.1Sponsor's protocol code numberMED3-201601
    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 SponsorRheinische Friedrich-Wilhelms-Universität Bonn
    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 GmbH & Co. KGaA
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationStudienzentrale Studienzentrum Bonn (SZB)
    B.5.2Functional name of contact pointMarius Krauthausen
    B.5.3 Address:
    B.5.3.1Street AddressVenusberg-Campus 1
    B.5.3.2Town/ cityBonn
    B.5.4Telephone number004922828711775
    B.5.5Fax number004922828716039
    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 No
    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
    D.3.2Product code BMS-936558-01
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    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. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product No
    D. ATIMP (i.e. one involving a medical device) No
    D. 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
    Patients with resectable advanced stage HNSCC (T1–T4 N0-N2 M0) with intermediate risk (resection margins > 5 mm, no perineural invasion and no extracapsular evasion) for whom definite RT post surgery would be standard of care.
    E.1.1.1Medical condition in easily understood language
    Patients with resectable advanced stage HNSCC (T1–T4 N0-N2 M0) with intermediate risk for whom definite RT post surgery would be standard of care.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level PT
    E.1.2Classification code 10060121
    E.1.2Term Squamous cell carcinoma of head and neck
    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 analyze response of intermediate risk HNSCC patients after surgery to treatment with nivolumab plus radiotherapy versus radiotherapy alone.
    E.2.2Secondary objectives of the trial
    • To assess overall survival in response to experimental treatment versus standard treatment
    • To assess safety of nivolumab plus radiotherapy compared to radiotherapy alone
    • To assess quality of life of experimental treatment versus standard treatment

    Exploratory Objectives:
    • Identification of antigens recognized by the immune system under nivolumab plus radiotherapy compared to radiotherapy alone
    • To identify immunological biomarker for treatment response and prognosis

    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Histologically confirmed squamous cell carcinoma of the head and neck region (oral cavity, pharynx, larynx), T1–T4 N0-N2 M0, with intermediate risk and curative intent for which post operative adjuvant radiation therapy would be standard of care. No presence of the following risk factors: extracapsular growth of the lymph nodes or positive margins; (in these cases an adjuvant post operation platinum based chemoradiation therapy is recommended). Close margins (< 5 mm) of the main specimen or focally positive margins of the main specimen are permitted if subsequent margins are negative. Additionally, close margins (< 5 mm) of the main specimen are allowed under certain circumstances, see inclusion criteria (3).
    2. CT scan or MRI (MRI in the case of contrast agent allergy) of the neck and thorax within 80 days prior to randomization (preoperative or postoperative). CT of the abdomen (or ultrasound abdomen) within 80 days prior to randomization (preoperative or postoperative).
    3. Margin(s) of resection > 5 mm; margins < 5 mm are only allowed if a) subsequently confirmed as a negative margin or b) the close margin adjoins a clear anatomical border (e.g. bone). Similary, patients whose tumors had focally positive margins in the main specimen are eligible if margins from reexcised samples in the region of the positve margin are negative.
    4. Males and Females  18 years of age with an Eastern Cooperative Oncology Group (ECOG) performance status 1.
    5. Documentation of p16-positive or p16-negative disease to determine human papillomavirus (HPV) status of tumor for SCCHN.
    6. Be free of signs of remaining cancer.
    7. Tumor tissue must be available for PD-L1 expression analysis (Randomisation < 1 % versus ≥ 1 % expression of PD-L1) and other biomarker correlative studies.
    8. Immunosuppressive doses of systemic medication, such as steroids or absorbed topical steroids (doses > 10 mg/day prednisone or equivalent) must be discontinued at least 2 weeks before study drug administration.
    9. Have adequate organ function
    10. Screening laboratory values must meet the following criteria (using CTCAE v4):
    • WBC 2000/μL
    • Neutrophils 1500/μL
    • Platelets 100 x103/μL
    • Hemoglobin  9.0 g/dL
    • Serum creatinine 1.5 x ULN or creatinine clearance (CrCl) > 40 mL/min
    • AST/ALT 3 x ULN
    • Total Bilirubin 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL).
    11. Subjects must have resting baseline O2 saturation by pulse oximetry of ≥ 92 % at rest.
    E.4Principal exclusion criteria
    1. Histologically confirmed recurrent or metastatic carcinoma or primary of the nasopharynx or salivary gland or non-squamous histologies (e.g. mucosal melanoma) are not allowed.
    2. One of the following risk factors: extracapsular growth of the lymph nodes, or positive margins (post operative adjuvant platinum based chemoradiation therapy recommended).
    3. Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
    4. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
    5. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
    6. Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
    7. Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
    8. Patient is the recipient of an organ/bone marrow transplant
    9. Positive test for Hepatitis B virus surface antigen (HB sAg) or active Hepatitis C (presence of HCV RNA in case of positive HCV antibody) or positive testing for HIV (HIV antibodies).
    10. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
    11. History of allergy to study drug components.
    12. History of severe hypersensitivity reaction to any monoclonal antibody.
    13. Prisoners or subjects who are involuntarily incarcerated.
    14. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.
    15. Current pregnancy or lactating females.
    16. Females of childbearing potential, who are not using and not willing to use medically reliable methods of contraception for the entire study duration (such as oral, injectable or implantable contraceptives, or intrauterine contraceptive devices) unless they are surgically sterilized/hysterectomized or there are any other criteria sufficiently reliable by the investigator in individual cases.
    17. The subject received an investigational drug within 30 days prior to inclusion into this study.
    18. The subject is unwilling to provide informed consent or unwilling or unable to follow the procedures outlined in the protocol.
    19. The subject is mentally or legally incapacitated.
    E.5 End points
    E.5.1Primary end point(s)
    Disease free survival measured from time of randomization to first signs of local recurrence, regional or distant metastasis, second primary or death, whichever comes first.
    E.5.1.1Timepoint(s) of evaluation of this end point
    36 month after randomization
    E.5.2Secondary end point(s)
    • Overall survival, measured from time of randomisation to death of any cause
    • Adverse events (graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, V 4.0)
    • Quality of Life will be evaluated by standardized questionnaires QLQ-C30, EQ-5D and head and neck specific module QLQ-H&N35

    Exploratory endpoints:
    • Immunological monitoring will consist of serum biomarkers, including but not limited to T cell response, characterization of immune cell subsets in peripheral blood, soluble PD-L1, soluble PD-L2, IL-2, inflammatory factors, rheumatoid factors.
    E.5.2.1Timepoint(s) of evaluation of this end point
    36 month after randomization,
    over all survival will by assessed by long-term follow-up till death of any 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. 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 Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E. description
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned15
    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
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years8
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    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: 176
    F.1.3Elderly (>=65 years) No
    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 state176
    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)
    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 Decision2017-10-11
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-09-05
    P. End of Trial
    P.End of Trial StatusOngoing
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