Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

  • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).


    The EU Clinical Trials Register currently displays   43851   clinical trials with a EudraCT protocol, of which   7283   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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2018-001974-76
    Sponsor's Protocol Code Number:MK-3475-630
    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:2019-01-18
    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 number2018-001974-76
    A.3Full title of the trial
    A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate Pembrolizumab Versus Placebo as Adjuvant Therapy Following Surgery and Radiation in Participants with High-risk Locally Advanced Cutaneous Squamous Cell Carcinoma (LA cSCC) (KEYNOTE-630)
    Estudio de fase III, aleatorizado, doble ciego y controlado con placebo para evaluar pembrolizumab frente a un placebo como tratamiento adyuvante después de cirugía y radioterapia del carcinoma epidermoide cutáneo localmente avanzado (CEC LA) de alto riesgo, MK3475-630.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Pembrolizumab as adjuvant therapy for resectable high-risk LA cSCC
    Pembrolizumab como tratamiento adyuvante del CEC LA de alto riesgo resecable.
    A.3.2Name or abbreviated title of the trial where available
    Pembrolizumab as adjuvant therapy for resectable high-risk LA cSCC
    Pembrolizumab como tratamiento adyuvante del CEC LA de alto riesgo resecable
    A.4.1Sponsor's protocol code numberMK-3475-630
    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 SponsorMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
    B.1.3.4CountryUnited States
    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 supportMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMerck Sharp & Dohme de España S.A.
    B.5.2Functional name of contact pointInvestigación Clínica
    B.5.3 Address:
    B.5.3.1Street AddressCalle Josefa Valcárcel, 38
    B.5.3.2Town/ cityMadrid
    B.5.3.3Post code28027
    B.5.3.4CountrySpain
    B.5.4Telephone number+34913210600
    B.5.5Fax number+34913210590
    B.5.6E-mailensayos_clinicos@merck.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 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 namePEMBROLIZUMAB
    D.3.2Product code MK-3475
    D.3.4Pharmaceutical form 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 INNPEMBROLIZUMAB
    D.3.9.1CAS number 1374853-91-4
    D.3.9.2Current sponsor codeMK-3475
    D.3.9.4EV Substance CodeSUB167136
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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) Yes
    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 KEYTRUDA (pembrolizumab, MK-3475)
    D.2.1.1.2Name of the Marketing Authorisation holderMerck Sharp & Dohme B.V.
    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 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 INNPEMBROLIZUMAB
    D.3.9.1CAS number 1374853-91-4
    D.3.9.2Current sponsor codeMK-3475
    D.3.9.4EV Substance CodeSUB167136
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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) Yes
    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 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
    Resectable high-risk locally advanced cutaneous squamous cell carcinoma (LA cSCC)
    carcinoma epidermoide cutáneo localmente avanzado (CEC LA) de alto riesgo,
    E.1.1.1Medical condition in easily understood language
    High-risk Locally Advanced cutaneous squamous cell carcinoma (non-melanoma skin cancer)
    carcinoma epidermoide cutáneo localmente avanzado (cáncer de piel no melanoma)
    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 10041823
    E.1.2Term Squamous 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 compare the recurrence-free survival (RFS), as assessed by the investigator and confirmed by biopsy, in individuals who receive pembrolizumab with individuals who receive placebo as adjuvant therapy
    Comparar la supervivencia sin recidiva (SSR), evaluada por el investigador y confirmada mediante biopsia, entre los sujetos que reciban pembrolizumab y los que reciban placebo como tratamiento adyuvante.
    E.2.2Secondary objectives of the trial
    1. To compare overall survival (OS) in individuals who receive pembrolizumab with individuals who receive placebo as adjuvant therapy
    2. To compare mean change from baseline in health-related quality of life (HRQoL) scores from the European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30, in individuals who receive pembrolizumab with individuals who receive placebo as adjuvant therapy
    3. To determine the safety and tolerability of pembrolizumab as adjuvant therapy in study participants
    1. Comparar la supervivencia global (SG) entre los sujetos que reciban pembrolizumab y los que reciban placebo como tratamiento adyuvante
    2. Comparar la variación media con respecto al momento basal de la puntuación de la escala de calidad de vida relacionada con la salud (CVRS) del cuestionario de calidad de vida (QLQ) C30 de la Organización Europea para la Investigación y el Tratamiento del Cáncer (EORTC) entre los sujetos que reciban pembrolizumab y los que reciban el placebo como tratamiento adyuvante.
    3. Determinar la seguridad y la tolerabilidad de pembrolizumab como tratamiento adyuvante en los participantes en el estudio
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Merck will conduct Future Biomedical Research on DNA (Blood and tissue) specimens collected during this clinical trial. Such research is for biomarker testing to address emergent questions not described elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented subjects. The objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding of diseases and/or their therapeutic treatments. The overarching goal is to use such information to develop safer, more effective drugs, and/or to ensure that subjects receive the correct dose of the correct drug at the correct time
    Merck realizará investigaciones biomédicas futuras con las muestras
    obtenidas (sangre y tejido) para tal finalidad durante este ensayo
    clínico. Estas investigaciones tendrán por objeto el análisis de
    biomarcadores con el fin de abordar aspectos nuevos que no se
    describen en otras partes del protocolo (como parte del ensayo
    principal) y solo se llevarán a cabo en muestras de los pacientes que
    hayan otorgado el consentimiento correspondiente. El objetivo de la
    obtención de muestras para investigaciones biomédicas futuras es
    estudiar e identificar biomarcadores que proporcionen información a los
    científicos sobre las enfermedades y sus tratamientos. El objetivo último
    es utilizar tal información para desarrollar fármacos más seguros y
    eficaces o para garantizar que los sujetos reciban la dosis correcta del
    fármaco en el momento preciso.
    E.3Principal inclusion criteria
    1. Participants must have histologically confirmed cSCC as the primary site of malignancy (metastatic skin involvement from another primary cancer or from an unknown primary cancer is not permitted)
    2. Participant must have undergone complete macroscopic resection of all known cSCC disease with or without microscopic positive margins. Surgery may consist of 1 or a combination of the following:
    a. Resection of the primary lesion
    b. Any type of neck dissection(s)
    c. Any type of parotidectomy (superficial, total, partial)
    3. Participant must have histologically confirmed LA cSCC with a high-risk feature(s) as the primary site of malignancy (metastatic skin involvement from another primary cancer or from an unknown primary cancer is not permitted).
    High-risk features include at least 1 of the following:
    a) Histologically involved nodal disease that has at least 1 of the following features:
    • Any extracapsular extension
    • ≥3 regional lymph nodes per primary site (affected regional sites and associated draining lymph nodes)
    • 1-2 involved lymph nodes with any node ≥3 cm in greatest diameter, independent of extracapsular extension
    b) Any index tumor with ≥2 of the following high risk features:
    • Tumor ≥4 cm with a depth >6 mm
    • Multi-focal perineural invasion for nerves of <0.1 mm diameter or any involved nerve ≥0.1 mm diameter
    • Invasion beyond subcutaneous fat
    • Poor differentiation and/or sarcomatoid and/or spindle cell histology
    • Recurrent disease (any cSCC that recurs within 3 years in the previously surgically or topically treated area)
    c) Any gross cortical bone invasion or skull base invasion and/or skull base foramen invasion
    d) Any index tumor that is resected with microscopic residual positive surgical margins
    4. Participant must have completed adjuvant RT for LA cSCC with last dose of RT ≥4 weeks and ≤16 weeks from randomization
    5. Participant must have completed at least 50 Gy 25 fractions of adjuvant RT for LA cSCC prior to study entry
    6. Participant is disease-free as assessed by the investigator with complete radiographic staging assessment ≤28 days from randomization
    7. Participant is male or female and at least 18 years of age at the time of signing the informed consent
    8. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
    • A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
    - Is not a woman of childbearing potential (WOCBP)
    OR
    - Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis),during the intervention period and for at least 120 days after the last dose of study intervention The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention
    - A WOCBP must have a negative highly sensitive pregnancy test (as required by local regulations) within 72 hours before the first dose of study intervention
    - If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive
    9. Participant (or legally acceptable representative, if applicable) provides written informed consent for the study. The participant may also provide consent for future biomedical research. However, the participant may participate in the main study without participating in future biomedical research
    10. Participant provides a tumor tissue sample adequate for PD-L1 testing as determined by central laboratory testing. This tissue sample may be obtained from either the surgical resection, or a prior archival tissue specimen not previously irradiated. FFPE tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue
    11. Participant has a life expectancy of greater than 3 months.
    12. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 10 days prior to treatment initiation.
    13. Participant has adequate organ function.Specimens must be collected within 10 days prior to the start of study treatment
    1. Tener un CEC confirmado histológicamente como foco primario de la neoplasia maligna (no se permite la afectación cutánea metastásica por otro cáncer primario o por un cáncer primario desconocido).
    2. Haberse sometido a una resección macroscópica completa de todo CEC conocido, con o sin positividad microscópica de los bordes. La cirugía puede consistir en una o más de lo siguiente:
    a. Resección de la lesión primaria
    b. Disección cervical de cualquier tipo.
    c. Parotidectomía de cualquier tipo de (superficial, total o parcial).
    3. Tener un CEC confirmado histológicamente con características de alto riesgo como foco primario de la neoplasia maligna (no se permite la afectación cutánea metastásica por otro cáncer primario o por un cáncer primario desconocido). Las características de alto riesgo son al menos una de las siguientes:
    a) Afectación ganglionar histológica con al menos una de las características siguientes:
    • Extensión extracapsular de cualquier tipo.
    • Al menos 3 ganglios linfáticos regionales por foco primario (regiones afectadas y sus ganglios linfáticos correspondientes).
    • Afectación de 1 o 2 ganglios linfáticos si alguno de ellos es ≥ 3 cm de diámetro mayor, con independencia de si hay extensión extracapsular.
    b) Cualquier tumor inicial con dos o más de las siguientes características de alto riesgo:
    • Tumor ≥ 4 cm con 6 mm de profundidad.
    • Invasión perineural multifocal en nervios de menos de 0,1 mm de diámetro o afectación de cualquier nervio ≥ 0,1 mm de diámetro.
    • Invasión más allá del tejido adiposo subcutáneo.
    • Escasa diferenciación o características histológicas de carcinoma sarcomatoide o de células fusiformes.
    • Enfermedad recidivante (cualquier CEC que reaparezca en los 3 años siguientes en la zona tratada quirúrgicamente o por vía tópica).
    c) Invasión macroscópica del hueso cortical o invasión de la base del cráneo o de un agujero de la base del cráneo.
    d) Cualquier tumor inicial resecado con positividad residual microscópica de los bordes quirúrgicos.
    4. Haber completado la RT adyuvante para el CEC LA, habiendo recibido la última dosis entre 4 y 16 semanas antes de la aleatorización.
    5. Haber completado al menos 50 Gy en 25 fracciones de RT adyuvante para el CEC LA antes de incorporarse al estudio.
    6. No presentar enfermedad según lo determinado por el investigador mediante una evaluación radiológica completa de estadificación efectuada en los 28 días previos a la aleatorización.
    7. Ser un varón o una mujer de al menos 18 años en el momento de la firma del consentimiento informado.
    8. El uso de anticonceptivos por las mujeres deberá cumplir la normativa local sobre métodos anticonceptivos para los participantes en estudios clínicos.
    • Una mujer podrá participar si no está embarazada, no está amamantando y cumple al menos una de las condiciones siguientes:
    - No es una mujer en edad fértil (MEF).
    O
    - Es una MEF y utiliza un método anticonceptivo muy eficaz (con un índice de fallos < 1% anual) o practica la abstinencia de relaciones heterosexuales como modo de vida preferido y habitual (abstinencia a largo plazo y persistente), durante el período de intervención y hasta al menos 120 días después de la última dosis de la intervención del estudio. El investigador deberá evaluar la posibilidad de fracaso del método anticonceptivo (es decir, incumplimiento, inicio reciente) en relación con la primera dosis de la intervención del estudio.
    - Las MEF deberán dar negativo en una prueba de embarazo de alta sensibilidad (según exija la normativa local) en las 72 horas previas a la primera dosis de la intervención del estudio.
    - Cuando el resultado de una prueba en orina no pueda confirmarse que es negativo (por ejemplo, resultado ambiguo), será necesario hacer una prueba de embarazo en suero. En tal caso, la participante será excluida si el resultado de la prueba de embarazo en suero es positivo.
    9. Otorgar (el participante o su representante legal cuando proceda) el consentimiento informado por escrito para el estudio. El participante también podrá otorgar su consentimiento para las investigaciones biomédicas futuras. No obstante, se podrá participar en el estudio principal sin necesidad de hacerlo en las investigaciones biomédicas futuras.
    10. Proporcionar una muestra de tejido tumoral adecuada para el análisis de PD-L1 según lo determinado por el laboratorio central. Esta muestra de tejido podrá obtenerse de la pieza
    resección quirúrgica o de una muestra de tejido de archivo no irradiada previamente. Se prefieren los bloques de tejido FFIP a los cortes. Se prefiere el uso de biopsias recientes al tejido de archivo.
    11. Tener una esperanza de vida mayor de 3 meses.
    12. Tener un estado funcional según el ECOG de 0 o 1 en los 10 días previos al inicio del tratamiento.
    13. Presentar una función orgánica adecuada. Las muestras se obtendrán en los 10 días previos al comienzo del tratamiento del estudio.
    E.4Principal exclusion criteria
    1. Has macroscopic residual cSCC after surgery and/or recurrence with active cSCC disease before randomization
    2. Has any other histologic type of skin cancer other than invasive cSCC, eg, basal cell carcinoma that has not been definitively treated with surgery or radiation, Bowen’s disease, MCC, melanoma
    3. A WOCBP who has a positive urine pregnancy test within 72 hours before the first dose of study treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive
    4. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another costimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137)
    5. Has received prior systemic anticancer therapy including investigational agents for cSCC within 4 weeks prior to randomization
    6. Participant must have recovered from all radiation-related toxicities, not have required corticosteroids, and not have had radiation pneumonitis
    7. Has received a live vaccine within 30 days prior to the first dose of study treatment.Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed
    8. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
    9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
    10. Has a diagnosed and/or treated additional malignancy within the past 5 years prior to randomization
    11. Has known active central nervous system metastases and/or carcinomatous meningitis
    12. Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients
    13. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
    14. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
    15. Has an active infection requiring systemic therapy
    16. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority
    17. Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (HCV; defined as HCV RNA [qualitative] is detected) infection
    18. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
    19. Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study
    20. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
    21. Has had an allogeneic tissue/solid organ transplant
    CEC activo antes de la aleatorización.
    2. Presencia de cáncer de piel de cualquier otro tipo histológico distinto del CEC invasivo, por ejemplo, carcinoma basocelular no tratado definitivamente con cirugía o radioterapia, enfermedad de Bowen, CCM o melanoma.
    3. En las mujeres en edad fértil, resultado positivo en una prueba de embarazo en orina realizada en las 72 horas previas a la primera dosis del tratamiento del estudio. Si el resultado de la prueba en orina es positivo o no puede confirmarse que sea negativo, será necesario hacer una prueba de embarazo en suero. En tal caso, la participante será excluida si el resultado de la prueba de embarazo en suero es positivo.
    4. Tratamiento previo con un fármaco anti-PD-1, anti-PD-L1 o anti-PD-L2 o con un fármaco dirigido contra otro receptor de los linfocitos T coestimulador o coinhibidor (como CTLA-4, OX-40 o CD137).
    5. Recepción de un tratamiento antineoplásico sistémico previo para el CEC, incluidos fármacos en investigación, en las cuatro semanas previas a la aleatorización.
    6. Los participantes deberán haberse recuperado de toda la toxicidad relacionada con la radioterapia, no haber necesitado corticoides y no haber sufrido una neumonitis por radiación.
    7. Recepción de una vacuna de microorganismos vivos en los 30 días previos a la administración de la primera dosis del tratamiento del estudio. Algunos ejemplos de vacunas de microorganismos vivos son, entre otros, los siguientes: vacuna contra el sarampión, antiparotídica, antirrubeólica, contra la varicela, contra la fiebre amarilla, antirrábica, bacilo de Calmette-Guérin (BCG) y antitifoidea. Las vacunas inyectables contra la gripe estacional contienen, por lo general, virus muertos y están permitidas; en cambio, las vacunas antigripales intranasales (p. ej., FluMist®) son vacunas de virus vivos atenuados y no están permitidas.
    8. Participación activa o pasada en un estudio de un fármaco en investigación o uso de un dispositivo en investigación en las cuatro semanas previas a la administración de la primera dosis del tratamiento del estudio.
    9. Diagnóstico de inmunodeficiencia o recepción de tratamiento sistémico crónico con esteroides (en dosis superiores a 10 mg diarios de prednisona o un equivalente) o cualquier otra forma de tratamiento inmunodepresor en los siete días previos a la primera dosis del fármaco del estudio.
    10. Diagnóstico o tratamiento de un tumor maligno adicional en los 5 años previos a la aleatorización.
    11. Presencia de metástasis activas conocidas en el sistema nervioso central o meningitis carcinomatosa.
    12. Hipersensibilidad grave (grado ≥ 3) a pembrolizumab o a cualquiera de sus excipientes
    13. Presencia de una enfermedad autoinmunitaria activa que ha precisado tratamiento sistémico (es decir, fármacos modificadores de la enfermedad, corticoides o inmunodepresores) en los dos últimos años. El tratamiento de reposición (por ejemplo, tiroxina, insulina o corticoides en dosis fisiológicas por insuficiencia suprarrenal o hipofisaria) no se considera una forma de tratamiento sistémico y se permitirá su uso.
    14. Antecedentes de neumonitis (no infecciosa) que haya precisado la administración de esteroides o presencia de una neumonitis activa.
    15. Infección activa con necesidad de tratamiento sistémico.
    16. Antecedentes de infección por el virus de la inmunodeficiencia humana (VIH). No es necesario realizar pruebas de VIH a menos que lo exijan las autoridades sanitarias locales.
    17. Antecedentes de infección por el virus de la hepatitis B (reactividad del antígeno de superficie del virus de la hepatitis B [HBsAg]) o infección activa por el virus de la hepatitis C (definida como detección de ARN del virus de la hepatitis C [VHC] [cualitativo]).
    18. Antecedentes o datos presentes de cualquier proceso, tratamiento o anomalía analítica que, en opinión del investigador responsable del tratamiento, podría confundir los resultados del estudio, dificultar la participación durante la totalidad del estudio o motivar que la participación no sea lo más conveniente para el posible participante.
    19. Presencia de un trastorno psiquiátrico o por abuso de sustancias que podría dificultar la capacidad del participante para colaborar en el cumplimiento de los requisitos del estudio.
    20. Embarazo, período de lactancia o intención de concebir o engendrar un hijo durante el período previsto del estudio, desde la visita de selección hasta 120 días después de la última dosis del tratamiento del estudio.
    21. Recepción de un alotrasplante de órgano sólido o tejidos.
    E.5 End points
    E.5.1Primary end point(s)
    Recurrence-free survival (RFS) as assessed by the investigator and confirmed by biopsy
    Comparar la supervivencia sin recidiva (SSR), evaluada por el investigador y confirmada mediante biopsia.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Up to approximately 60 months for the evaluation of recurrence-free survival
    Hasta 60 meses de supervivencia sin recidiva (SSR)
    E.5.2Secondary end point(s)
    1. Overall Survival (OS)
    2. Change from baseline in European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
    3. Percentage of participants who experience an adverse event (AE)
    4. Percentage of participants who discontinue study treatment due to an adverse event (AE)
    1.Supervivencia global (SG)
    2.Comparar la variación media con respecto al momento basal de la puntuación de la escala de calidad de vida relacionada con la salud (CVRS) del cuestionario de calidad de vida (QLQ) C30 de la Organización Europea para la Investigación y el Tratamiento del Cáncer (EORTC)
    3.Porcentaje de pacientes que experimenta Acontecimientos adversos (AA).
    4.Porcentaje de pacientes que suspenden el tratamiento del estudio por Acontencimientos Adversos.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Up to approximately 60 months for the evaluation of Overall Survival
    2. Baseline and up to approximately 60 months for the evaluation of EORTC QLQ-C30
    3. Up to approximately 63 months for the evaluation of adverse events
    4. Up to approximately 38 months for the evaluation of discontinuations
    1.Hasta 60 meses para la evaluación de la Supervivencia Global
    2.Desde el momento basal hasta 60 meses para la evaluación del cuestionario de calidad de vida (QLQ) C30
    3.Hasta 63 meses para la evaluación de los acontencimientos adversos
    4. Hasta 38 meses para la evaluación de las suspensions del tratamiento
    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 Yes
    E.6.11Pharmacogenomic Yes
    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) 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 Yes
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    open-label retreatment
    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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA65
    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
    Brazil
    Canada
    Colombia
    France
    Germany
    Greece
    Hungary
    Israel
    Italy
    Mexico
    Norway
    Portugal
    Romania
    Russian Federation
    Spain
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years7
    E.8.9.1In the Member State concerned months1
    E.8.9.1In the Member State concerned days15
    E.8.9.2In all countries concerned by the trial years8
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial 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: 220
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 350
    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 state32
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 285
    F.4.2.2In the whole clinical trial 570
    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
    Ninguna
    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 Decision2019-02-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-02-04
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA