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    Summary
    EudraCT Number:2017-002755-29
    Sponsor's Protocol Code Number:CA209-9DX
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2018-01-04
    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 ConcernedSpain - AEMPS
    A.2EudraCT number2017-002755-29
    A.3Full title of the trial
    A Phase 3, Randomized, Double-blind Study of Adjuvant Nivolumab versus Placebo for Participants with Hepatocellular Carcinoma Who Are at High Risk of Recurrence after Curative Hepatic Resection or Ablation (CheckMate 9DX: CHECKpoint pathway and nivoluMAb clinical Trial Evaluation 9DX)
    Estudio en fase III, aleatorizado y doble ciego de nivolumab adyuvante frente a placebo para participantes con carcinoma hepatocelular que presentan un riesgo alto de recaída después de la resección o la ablación hepática con intención curativa [Evaluación en ensayo clínico de la vía de punto de control y el nivolumab 9DX]
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 3 Study of Nivolumab versus Placebo for Participants with Hepatocellular Cancer Who Are at High Risk of Recurrence after Hepatic Resection or Ablation
    Estudio en fase III, aleatorizado y doble ciego de nivolumab adyuvante frente a placebo para participantes con carcinoma hepatocelular que presentan un riesgo alto de recaída después de la resección o la ablación hepática con intención curativa
    A.3.2Name or abbreviated title of the trial where available
    CheckMate 9DX
    A.4.1Sponsor's protocol code numberCA209-9DX
    A.5.3WHO Universal Trial Reference Number (UTRN)U1111-1198-6193
    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 SponsorBristol-Myers Squibb International Corporation
    B.1.3.4CountryBelgium
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportBristol-Myers Squibb International Corporation
    B.4.2CountryBelgium
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBristol-Myers Squibb International Corporation
    B.5.2Functional name of contact pointGCT-SU
    B.5.3 Address:
    B.5.3.1Street AddressParc de l'Alliance - Avenue de Finlande, 4
    B.5.3.2Town/ cityBraine-l'Alleud
    B.5.3.3Post code1420
    B.5.3.4CountryBelgium
    B.5.6E-mailclinical.trials@bms.com
    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 Opdivo (100 mg/10 ml)
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers Squibb Pharma EEIG
    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
    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.3.9.2Current sponsor codeBMS-936558-01
    D.3.9.3Other descriptive nameBMS-936558, MDX1106, ONO-4538
    D.3.9.4EV Substance CodeSUB32944
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection/infusion
    D.8.4Route of administration of the placeboIntravenous use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection/infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Hepatocellular Carcinoma
    Carcinoma Hepatocelular
    E.1.1.1Medical condition in easily understood language
    Liver cancer
    Cáncer de Hígado
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10073071
    E.1.2Term Hepatocellular 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 compare recurrence-free survival (RFS) (based on BICR assessment) of nivolumab vs placebo in all randomized participants.
    • Comparar la supervivencia libre de recaída (SLR) (mediante la evaluación de la revisión central independiente enmascarada [RCIE]) de nivolumab frente a placebo en todos los participantes aleatorizados.
    E.2.2Secondary objectives of the trial
    • To compare overall survival (OS) of nivolumab vs placebo in all randomized participants.
    • To evaluate time to recurrence (TTR) (based on BICR assessment) of nivolumab vs placebo in all randomized participants.
    • Comparar la supervivencia global (SG) de nivolumab frente a placebo en todos los participantes aleatorizados.
    • Evaluar el tiempo hasta la recaída (THR) (mediante la evaluación de la RCIE) de nivolumab frente a placebo en todos los participantes aleatorizados.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Males and females, ages 18 or older.
    2. Participants must have a first diagnosis of HCC amenable for management with curative intent by resection or local ablation.
    3. Participants are eligible to enroll if they have non-viral related-HCC, or if they have HBV-HCC, or HCV-HCC
    4. Participants are eligible to enroll if they have undergone:
    i) Hepatic resection and have the following tumor characteristics: up to three tumors, at least one with a diameter > 5 cm OR none with a diameter > 5 cm but with confirmation of microvascular invasion or poorly /undifferentiated HCC; or more than three tumors, none with a diameter > 5 cm
    ii) Local ablation [radiofrequency ablation (RFA) or microwave ablation (MWA)] and have the following tumor characteristics: solitary tumor > 3cm but <=5 cm; OR Multiple tumors (up to 4), none with a diameter > 5 cm
    5. Participants must have complete resection response, or must have achieved radiologically documented complete resection after local ablation.
    6. All participants are required to have imaging studies confirming disease-free status at least 4 weeks after either complete tumor removal after surgical resection or local ablation, and within 4 weeks prior to randomization.
    7. Child-Pugh Score 5 or 6
    8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
    1. Hombres y mujeres de 18 años en adelante.
    2. Los participantes deben tener un primer diagnóstico de CHC susceptible de control con intención curativa mediante resección o ablación local.
    3. Los participantes serán aptos para su inclusión si presentan CHC no relacionado con virus o si padecen CHC-VHB o CHC-VHC.
    4. Los participantes serán aptos para su inclusión si se han sometido a:
    i) Resección hepática con las siguientes características tumorales: hasta tres tumores, al menos uno de un diámetro >5 cm O BIEN ninguno con un diámetro >5 cm, pero con confirmación de invasión microvascular o de CHC mal diferenciado o indiferenciado; o más de tres tumores, ninguno con un diámetro >5 cm.
    ii) Ablación local (ablación por radiofrecuencia [ARF] o ablación por microondas [AMO]) y presentar las características tumorales siguientes: tumor único >3 cm, pero <=5 cm; O BIEN varios tumores (hasta 4), ninguno de ellos con un diámetro >5 cm.
    5. Los participantes deben haber tenido una respuesta completa a la resección, o bien haber logrado una resección completa documentada radiológicamente tras la ablación local.
    6. Todos los participantes deben tener estudios de imágenes que confirmen su estado de ausencia de enfermedad al menos 4 semanas después de la extirpación completa del tumor tras una resección quirúrgica o una ablación local, y dentro de las 4 semanas anteriores a la aleatorización.
    7. Puntuación de Child-Pugh de 5 o 6.
    8. Estado funcional (EF) de 0 o 1 según la escala del Grupo Oncológico Cooperativo de la Costa Este (ECOG).
    E.4Principal exclusion criteria
    1. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
    2. Prior recurrence of HCC.
    3. Any evidence of tumor metastasis or co-existing malignant disease.
    4. Participants showing evidence of macrovascular invasion on imaging tests.
    5. Participants who have undergone a liver transplant or those who are in the waiting list for liver transplantation.
    6. Active co-infection with with both Hepatitis B and C, OR Hepatitis D and B
    7. Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
    8. Participants with an active, known or suspected autoimmune disease.
    9. Participants with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of start of study treatment.
    10. Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured.
    11. Participants previously receiving any prior therapy for HCC, including loco-regional therapies, before or after resection or ablation.
    12. Participants receiving or expected to receive IFN-based therapies during the study period.
    13. Positive pregnancy test.
    1. CHC fibrolamelar conocido, CHC sarcomatoide o tumor mixto de colangiocarcinoma y CHC.
    2. Recaída previa del CHC.
    3. Cualquier indicio de metástasis tumoral o de neoplasia maligna coexistente.
    4. Participantes que muestren indicios de invasión macrovascular en las pruebas de imágenes.
    5. Participantes sometidos a trasplante hepático o que estén en lista de espera para trasplante hepático.
    6. Coinfección activa de hepatitis B y C, O BIEN de hepatitis D y B.
    7. Antecedentes conocidos de pruebas positivas para el virus de la inmunodeficiencia humana (VIH) o síndrome de inmunodeficiencia adquirida (SIDA) conocido.
    8. Participantes con enfermedad autoinmune activa, conocida o sospechada.
    9. Participantes con una afección que requiera tratamiento sistémico con corticosteroides u otros inmunosupresores durante los 14 días previos al inicio del tratamiento del estudio.
    10. Neoplasia maligna previa activa dentro de los 3 años anteriores, excepto para los cánceres curables localmente que se hayan curado en apariencia.
    11. Participantes que hayan recibido anteriormente algún tratamiento para el CHC, incluidos los tratamientos locorregionales, antes o después de la resección o de la ablación.
    12. Participantes que estén recibiendo o que esperen recibir tratamientos a base de IFN durante el periodo del estudio.
    13. Prueba de embarazo positiva.
    E.5 End points
    E.5.1Primary end point(s)
    • Recurrence free survival (RFS), defined as the time from randomization to the first documented disease recurrence or death (by any cause), whichever occurs first
    . Supervivencia sin recaída (SSR), definida como el tiempo transcurrido desde la aleatorización hasta la primera recaída documentada de la enfermedad o la muerte (por cualquier causa), lo que suceda primero.
    E.5.1.1Timepoint(s) of evaluation of this end point
    RFS will be evaluated on an ongoing basis from randomization until recurrence
    La SSR se evaluará de forma permanente desde la aleatorización hasta la recaída.
    E.5.2Secondary end point(s)
    • OS, defined as the time between the date of randomization and the date of death (by any cause).
    • Time to Recurrence (TTR), defined as the time from randomization to the first documented disease recurrence
    • SG, definida como el tiempo transcurrido entre la fecha de la aleatorización y la fecha de la muerte (por cualquier causa).
    • Tiempo hasta la recaída (TTR), definido como el tiempo transcurrido desde la aleatorización hasta la primera recaída documentada de la enfermedad.
    E.5.2.1Timepoint(s) of evaluation of this end point
    OS: From the beginning of randomization period up to date of event
    TTR: time from randomization to the first documented disease recurrence
    SG: Desde el inicio del periodo de aleatorización hasta la fecha del acontecimiento.
    TTR: tiempo transcurrido desde la aleatorización hasta la primera recaída documentada de la enfermedad.
    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 Yes
    E.6.7Pharmacodynamic Yes
    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
    Biomarker, immunogenicity analysis and outcome research (OR) QoL questionnaires
    Biomarcador, análisis de inmunogenicidad e investigación de resultados (IR) Cuestionarios de calidad de vida
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    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 No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    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 Yes
    E.8.2.3Other No
    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 concerned9
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA69
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Argentina
    Australia
    Austria
    Belgium
    Brazil
    Canada
    China
    France
    Germany
    Hong Kong
    Italy
    Japan
    Korea, Republic of
    Mexico
    Poland
    Romania
    Russian Federation
    Singapore
    Spain
    Taiwan
    United Kingdom
    United States
    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
    La ultima visita del ultimo paciente
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days27
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days27
    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: 441
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 442
    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 state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 232
    F.4.2.2In the whole clinical trial 883
    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)
    At the end of the study, BMS will not continue to provide BMS supplied study treatment to participants/investigators unless BMS chooses to extend the study. The investigator should ensure that the participant receives appropriate standard of care to treat the condition under study.
    Al final del estudio, BMS no continuará brindando el tratamiento del estudio suministrado por BMS a los participantes / investigadores a menos que BMS decida extender el estudio. El investigador debe asegurarse de que el participante reciba el nivel de atención adecuado para tratar la afección bajo estudio.
    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 Decision2018-02-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-02-14
    P. End of Trial
    P.End of Trial StatusOngoing
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