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A Randomized Phase III Study of Pembrolizumab Given Concomitantly With Chemoradiation and as Maintenance Therapy Versus Chemoradiation Alone in Subjects With Locally Advanced Head and Neck Squamous Cell Carcinoma KEYNOTE 412

Studio Clinico

Patologia: Tumori della testa e del collo

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: 

Fase di studio: III

Richiesta mandatoria di tessuto: 

Linee di trattamento: Non applicabile

Criteri di inclusione: 

  • Has a pathologically proven new diagnosis of oropharyngeal p16 positive, oropharyngeal p16 negative, or larynx/hypopharynx/oral cavity (independent of p16) squamous cell carcinoma. Participants with oral cavity tumors need to have unresectable disease.
  • Has provided tissue for Programmed Cell Death Receptor Ligand 1 (PD-L1) biomarker analysis from a core or excisional biopsy
  • Has evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed by computed tomography scan or magnetic resonance imaging, based on RECIST version 1.1
  • Is eligible for definitive CRT and not considered for primary surgery based on investigator decision
  • Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 10 days prior to receiving the first dose of study therapy
  • Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study therapy
  • Female and male participants of reproductive potential must agree to use adequate contraception throughout the study period and for up to 180 days after the last dose of study therapy

Criteri di esclusione: 

  • Is currently participating or has participated in a study with an investigational agent or using an investigational device within 4 weeks of the first dose of study therapy
  • Has received prior therapy with an anti-Programmed Cell Death Receptor 1 (PD-1), anti-PD-L1, anti-Programmed Cell Death Receptor Ligand 2 (PD-L2) agent or with an agent directed to another co-inhibitory T-cell receptor or has previously participated in clinical studies with pembrolizumab
  • Has received a live vaccine within 30 days prior to the first dose of study therapy
  • Has cancer outside of the oropharynx, larynx, and hypopharynx or oral cavity, such as nasopharyngeal, sinus, other para-nasal, or other unknown primary head and neck cancer
  • Has had prior systemic therapy, targeted therapy, radiotherapy treatment or radical surgery for head and neck cancer under study
  • Has not recovered from major surgery prior to starting study therapy
  • Has known active Hepatitis B or C
  • Has known history of Human Immunodeficiency Virus (HIV)
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study therapy
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment.
  • Has history of a diagnosed and/or treated hematologic or primary solid tumor malignancy, unless in remission for at least 5 years prior to randomization
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has had previous allogeneic tissue/solid organ transplant
  • Has active infection requiring systemic therapy
  • Has a history of severe hypersensitivity reaction to pembrolizumab, Cisplatin or radiotherapy or their analogs
  • Is pregnant or breast feeding or expecting to conceive or father children throughout the study period and for up to 180 days after the last dose of study therapy

Numero di pazienti previsti: 

780 Pazienti in tutto il mondo

Schema di trattamento: 

Experimental: Pembrolizumab + Cisplatin + CRT

Comparator: Placebo + Cisplatin + CRT 

Trattamento sperimentale: 

Participants receive a priming dose of pembrolizumab before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants receive 2 doses of pembrolizumab and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also receive up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab.

Trattamento di controllo: 

Participants receive placebo before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants receive 2 doses of placebo and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also receive up to an additional 14 cycles of placebo alone for a total of 17 cycles of placebo.

Obiettivi primari dello studio: 

Event-free Survival (EFS) [ Time Frame: Up to 5 years ]

EFS is the time from the date of randomization to the date of first record of disease progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) or death.

Obiettivi secondari dello studio: 

 

  • Overall Survival (OS) [ Time Frame: Up to 5 years ]
    OS is the time from randomization to death due to any cause.
  • Adverse Events (AEs) [ Time Frame: From time of first dose of study treatment until the end of follow-up (up to 5 years) ]
    Number of participants experiencing any sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy
  • Treatment Discontinuations Due to AEs [ Time Frame: From time of first dose of study treatment until the end of treatment (up to 1 year) ]
    Number of participants discontinuing study drug due to an AE
  • Global Health Status/Quality of Life (GHS/QoL) [ Time Frame: Prior to the first dose of study treatment (Baseline) and at the time of last follow-up (up to 5 years) ]
    Change from baseline in GHS/QoL using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC QLQ-C30)
  • Swallowing, Speech, and Pain Symptoms [ Time Frame: Prior to the first dose of study treatment (Baseline) and at the time of last follow-up (up to 5 years) ]
    Change from baseline in swallowing, speech, and pain symptoms using the EORTC Head and Neck Questionnaire (EORTC QLQ-H&N35)

 

Centri partecipanti

Nord Italia

Azienda Ospedaliera San Paolo
Via Antonio di Rudinì 8 - 20142 Milano - MI
D.H. Oncologia Medica

Riferimento: Dr. Daris Ferrari
Telefono: 0281841
Email: daris.ferrari@ao-sanpaolo.it

 

IRCCS Istituto Nazionale dei Tumori
Via Venezian 1 - 20133 Milano - MI
U.O. Onc. Medica-Dip. Testa-Collo

Riferimento: Dr.ssa Lisa Licitra
Telefono: 0223902804
Email: lisa.licitra@istitutotumori.mi.it

 

Istituto Europeo di Oncologia
Via Ripamonti 435 - 20141 Milano - MI
Oncologia Medica Urogenitale e Cervico Facciale

Riferimento: Dr. Enrico Nolè
Telefono: 0257489460
Email: franco.nole@ieo.it

 

A.O.U. Policlinico di Modena
Via del Pozzo 71 - 41100 Modena - MO
Centro Oncol. Modenese

Riferimento: Dr.ssa Federica Bertolini
Telefono: 0594223252
Email: bertolini.federica@policlinico.mo.it

 

Istituto Oncologico Veneto IRCCS
Via Gattamelata 64 - 35128 Padova - PD
Oncologia Medica 2

Riferimento: Dr.ssa Maria Grazia Ghi
Email: mariagrazia.ghi@iov.veneto.it

 

IRCCS Policlinico San Matteo
Viale Golgi 19 - 27100 Pavia - PV

Riferimento: Dr.ssa Ilaria Imarisio
Telefono: 0382502544
Email: i.imarisio@smatteo.pv.it

 

Centro Italia

AOU Careggi
Largo Brambilla 3 - 50134 Firenze - FI

Riferimento: Prof. Lorenzo Livi
Telefono: 0557947264
Email: lorenzo.livi@unifi.it

 

Sud Italia e isole

Istituto Nazionale Tumori IRCCS Fondazione Pascale
Via Mariano Semmola - 80131 Napoli - NA
Oncologia Medica B

Riferimento: Dr. Francesco Caponigro
Telefono: 0815903822
Email: caponigrof@libero.it

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2016-003934-25 / NCT03040999

Data di inserimento: 26.02.2018

Data di aggiornamento: 06.02.2019

Promotore

Merck Sharp & Dohme Corp.

CRO

N.A.

Principal Investigator ITALIA

Istituto Europeo di Oncologia - Milano

Riferimento: Dr. Franco Nolè

Telefono: 0257489460

Email: franco.nole@ieo.it

Localita: Milanol

 

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