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    The EU Clinical Trials Register currently displays   36358   clinical trials with a EudraCT protocol, of which   5990   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2017-000424-10
    Sponsor's Protocol Code Number:UC-0130/1703
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2017-06-28
    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 ConcernedFrance - ANSM
    A.2EudraCT number2017-000424-10
    A.3Full title of the trial
    A Safety study of Nivolumab in Patients with Recurrent and/or Metastatic Platinum-refractory Squamous Cell Carcinoma of the Head and Neck (SCCHN).
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    _
    A.3.2Name or abbreviated title of the trial where available
    ORL09 - TOPNIVO
    A.4.1Sponsor's protocol code numberUC-0130/1703
    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 SponsorUNICANCER
    B.1.3.4CountryFrance
    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.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUNICANCER
    B.5.2Functional name of contact pointJessy DELAYE
    B.5.3 Address:
    B.5.3.1Street Address101, rue de Tolbiac
    B.5.3.2Town/ cityParis cedex 13
    B.5.3.3Post code75654
    B.5.3.4CountryFrance
    B.5.4Telephone number33144 23 55 77
    B.5.5Fax number33171 93 61 65
    B.5.6E-mailj-delaye@unicancer.fr
    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.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.11 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
    Patients with recurrent and/or metastatic platinum refractory Squamous Cell Carcinoma of the Head and Neck (SCCHN), with poor prognosis and no effective chemotherapy options.
    E.1.1.1Medical condition in easily understood language
    Head and Neck cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To estimate the incidence of high-grade (i.e. Grade 3-5 of CTCAE v4.0) adverse events of interest (AEI) in patients with recurrent and/or metastatic platinum refractory SCCHN treated with nivolumab in monotherapy. AEI are defined as adverse reactions known to be related to nivolumab (i.e. skin, endocrinopathy, astrointestinal, hepatic, renal, pulmonary, and hypersensitivity adverse events) and other adverse events not related to carcinoma progression or to intercurrent disease clearly identified.
    E.2.2Secondary objectives of the trial
    - To characterize the type and outcome of high-grade AEI in patients receiving nivolumab monotherapy (time of onset, time to resolution, need for immune modulating concomitant medication or hormone replacement, need for therapy stop temporary or definitively).
    - To estimate the rate of low-grade (i.e. 1-2) AEI
    - To estimate the efficacy of nivolumab in terms of Overall Survival (OS) and Progression Free Survival (PFS) in all treated patients and pre-defined sub-groups
    - To estimate investigator-assessed Objective Response Rate (ORR) during nivolumab treatment in all treated patients and pre-defined sub-groups, using RECIST 1.1 and iRECIST
    - To assess the proportion of pseudo-progression for the entire trial population and by pre-defined sub-groups
    - To study biological and radiological biomarkers of response or progression
    * See the sub-groups definition in STATISTICAL ANALYSIS (p. 9)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Adult men and women ≥ 18 years.
    2. Histologically confirmed recurrent and/or metastatic SCCHN (oral cavity, pharynx, larynx), stage III/IV and not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy).
    3. Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
    4. Documentation of p16-positive or p16-negative disease to determine human papillomavirus (HPV) status of tumor for SCC of the oropharynx
    5. Tumor progression or recurrence after a platinum therapy in the adjuvant (ie with radiation after surgery), primary (ie, with radiation), recurrent, or metastatic setting. In the adjuvant or primary setting, the recurrence must have occurred within 6 months after the last dose of platinum therapy. Clinical progression after platinum therapy is an allowable event for entry and is defined as progression of a lesion at least 10 mm in size that is amenable to caliper measurement (eg superficial skin lesion as per RECIST 1.1) or a lesion that has been visualized and photographically recorded with measurements and shown to have progressed.
    6. Measurable disease by CT or MRI per RECIST 1.1 criteria
    7. Prior curative radiation therapy must have been completed at least 4 weeks prior to study drug administration. Prior focal palliative radiotherapy must have been completed at least 2 weeks before study drug administration.
    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. Patients with brain metastases will be eligible if they are: asymptomatic, without edema, not on corticosteroids, have been treated and there is no magnetic resonance imaging (except where contraindicated in which CT scan is acceptable) evidence of progression for at least 4 weeks after treatment is complete
    10. Screening laboratory values must meet the following criteria (using CTCAE v4) and should be obtained within 7 days prior to the first study drug administration :
    a. WBC ≥ 2000/μL
    b. Polynuclear neutrophils ≥ 1.5 x 109/L
    c. Platelets≥ 75 x 109/L
    d. Hemoglobin ≥ 8.0 g/mL
    e. ALAT/ASAT≤ 3.0 x ULN in the absence of liver metastases or ≤ 5x ULN in the presence of liver metastases
    f. Total Bilirubin ≤ 1.5 x ULN (except Gilbert Syndrome : < 3.0 mg/dL)
    g. Creatinine clearance ≥ 40 mL/min (measured or calculated by Cockroft and Gault formula) or serum creatinine ≤2.0 x ULN
    11. Calcium levels must be normalized and maintained within normal limits for study entry and on treatment. Medical management of calcium levels is permitted. Note: Normal calcium levels may be based on ionized calcium or adjusted for albumin.
    12. Subjects with an initial magnesium < 0.5 mmol/L (1.2 mg/dL) may receive corrective magnesium supplementation but should continue to receive either prophylactic weekly infusion of magnesium and/or oral magnesium supplementation (eg, magnesium oxide) at the investigator’s discretion.
    13. Potentially reproductive patients must agree to use an effective contraceptive method or practice adequate methods of birth control or practice complete abstinence, 14 days before starting drug and while on treatment, and for at least 31 weeks (≈ 7 months) for males and 23 weeks (≈ 5 months) for females after the last dose of study drug. Azoospermic males and women of childbearing potential who are continuously not heterosexually active are exempt from contraceptive requirements.
    14. Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25IU/L or equivalent units of HCG) done within 24 hours prior to the first dosing.
    15. Women who are breastfeeding should discontinue nursing prior to the first dose of study drug and until 6 months after the last dose.
    16. Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses.
    17. Patients with social insurance coverage.
    E.4Principal exclusion criteria
    1. Histologically confirmed recurrent and/or metastatic carcinomas of the nasopharynx, squamous cell carcinoma of unknown primary, and salivary gland or non-squamous histologies (eg mucosal melanoma) are not allowed.
    2. 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.
    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 enrol.
    5. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first 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. Patients having received prior therapy with 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).
    7. Patients receiving anti-cancer therapies must be discontinued at least 2 weeks prior to administration of study drug. Palliative, focal radiation therapy, and immunosuppressive doses of systemic corticosteroids, except replacement organotherapy (hydrocortisone and fludrocortisone), must be discontinued at least 2 weeks before administration of study drug.
    8. All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to grade 1 (NCI CTCAE version 4) or baseline before administration of study drug. Subjects with toxicities attributed to systemic prior anticancer therapy which are not expected to resolve and result in long lasting sequelae, such as neuropathy after platinum based therapy, are permitted to enroll.
    9. Patients with positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
    10. Patients with positive tests for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating active or chronic infection.
    11. Use of non-oncology vaccines containing live virus for prevention of infectious diseases within 4 weeks prior to study drug. The use of the inactivated seasonal influenza vaccine (Fluzone®) is allowed.
    12. Known or underlying medical condition (e.g., a condition associated with diarrhea or acute diverticulitis) that, in the investigator’s opinion, would make the administration of study drug hazardous to the patient or obscure the interpretation of toxicity determination or adverse events.
    13. History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of oral drug intake (if applicable).
    14. Unwillingness to give written informed consent, unwillingness to participate, or inability to comply with the protocol for the duration of the study.
    15. Individuals deprived of liberty or placed under the authority of a tutor.
    16. Treatment with any other investigational agent, or participation in another clinical trial within 28 days, prior to first study drug administration and during the treatment period.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint of this study is the incidence of high-grade (CTCAE v4.0 Grade 3-4 and Grade 5) adverse events of interest (AEI), that are adverse reactions known to be related to nivolumab (i.e. skin, endocrinopathy, gastrointestinal, hepatic, renal, pulmonary, and hypersensitivity adverse events) and other adverse events not related to carcinoma progression or to intercurrent disease clearly identified.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The period of observation of adverse events of interest is the period of Nivolumab treatment and 100days after the end of treatment. The grade used for analysis is the highest grade of the AE observed during this period.
    E.5.2Secondary end point(s)
    - Time to onset of grade 3+ AEI,
    - Time to resolution of grade 3-4 AEI to grade 1
    - Rate of patients with at least one or more doses of nivolumab delayed (or cancelled) due to AE
    - Rate of patients with nivolumab definitively withdrawn due to AE
    - Rate of nivolumab-related deaths
    - Rate of patients who received immune modulating concomitant medication (e.g., corticosteroids (> 10 mg prednisone or equivalent), infliximab, cyclophosphamide, IVIG, mycophenolate mofetil, etc), or hormonal replacement therapy
    - Duration of all immune modulating medications given for the select event and summary of patients with resolution of AEs after initiating these therapies.
    - Rate of AEI of maximum grade 1-2
    - Overall survival (OS)
    - Progression free survival (PFS)
    - Objective response rate (ORR) (complete response and partial response according to RECIST 1.1 and to iRECIST) during nivolumab treatment
    - Pseudo progression as defined to a progression according to RECIST 1.1 under treatment (≥ 20% increase in the sum of diameters of target lesions or unequivocal progression of existing non target lesions or new lesion) that is not confirmed at the next evaluation done 4 to 6 weeks later using iRECIST.
    E.5.2.1Timepoint(s) of evaluation of this end point
    _
    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 Yes
    E.6.13.1Other scope of the trial description
    Study of biological and radiological biomarkers of response or progression
    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 No
    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 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 No
    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 concerned30
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months
    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: 100
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 73
    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 No
    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 state173
    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)
    none
    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 Decision2017-06-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-04-25
    P. End of Trial
    P.End of Trial StatusOngoing
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