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A Randomized, Double-Blind, Adaptive, Phase II/III Study of GSK3359609 in Combination With Pembrolizumab and 5FU-Platinum Chemotherapy Versus Placebo in Combination With Pembrolizumab Plus 5FU-Platinum Chemotherapy for First-Line Treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma - 209227

Studio Clinico

Patologia: Tumori della testa e del collo

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: 

Fase di studio: II, III

Richiesta mandatoria di tessuto: 

Linee di trattamento: Prima linea

Criteri di inclusione: 

- Histological or cytological documentation of HNSCC that was diagnosed as recurrent or metastatic and considered incurable by local therapies.
- Primary tumor location of the oral cavity, oropharynx, hypopharynx or larynx.
- No prior systemic therapy administered in the recurrent or metastatic setting (with the exception of systemic therapy completed > 6 months prior if given as part of multimodal treatment for locally advanced disease and no disease progression/recurrence within 6 months of the completion of curatively intended systemic treatment).
- Measurable disease.
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1.
- Adequate organ function.
- Life expectancy of at least 12 weeks.
- Female participants: must not be pregnant, not breastfeeding, and be either not a woman of childbearing potential (WOCBP); or be a WOCBP who agrees to use a highly effective method of birth control from 30 days prior to randomization and for at least 120 days after the last dose of study treatment.
- Male participants with female partners of child-bearing potential: must agree to use a highly effective contraception while receiving study treatment and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this periods.
- Provide tumor tissue from excisional or core biopsy (fine needle aspirates and bone biopsies are not acceptable) acquired within 2 years prior to randomization for PD-L1 immunohistochemistry (IHC) testing by central laboratory.
- Have PD-L1 IHC CPS status by central laboratory testing.
- Have results from testing of human papilloma virus (HPV) status for oropharyngeal cancer.

Criteri di esclusione: 

- Prior therapy with an anti-PD-1/L1/L2, anti-Inducible T Cell Co-Stimulatory Receptor (ICOS ) directed agent.
- Systemic approved or investigational anticancer therapy within 30 days or 5 half lives of the drug, whichever is shorter.
- Has high risk of bleeding.
- Active tumor bleeding
- Grade 3 or Grade 4 hypercalcemia.
- Major surgery <=28 days prior to randomization.
- Toxicity from previous anticancer treatment that includes: a. Grade 3/Grade 4 toxicity related to prior immunotherapy and that led to treatment discontinuation and toxicity related to prior treatment that has not resolved to <=Grade 1 (except alopecia, hearing loss, endocrinopathy managed with replacement therapy, and peripheral neuropathy which must be <=Grade 2).
- Received transfusion of blood products or administration of colony stimulating factors within 14 days prior to randomization.
- Central nervous system (CNS) metastases, with the following exception: Participants with asymptomatic CNS metastases who are clinically stable and have no requirement for steroids for at least 14 days prior to randomization.
- Invasive malignancy or history of invasive malignancy other than disease under study within the last 3 years with the exception of any other invasive malignancy for which the participant was definitively treated, has been disease-free for <=3 years, curatively treated non-melanoma skin cancer or successfully treated in situ carcinoma and/or low-risk early stage prostate cancer.
- Autoimmune disease or syndrome that required systemic treatment within the past 2 years.
- Has a diagnosis of immunodeficiency or is receiving systemic steroids (>10 milligram (mg) oral prednisone or equivalent) or other immunosuppressive agents within 7 days prior to randomization.
- Receipt of any live vaccine within 30 days prior randomization.
- Prior allogeneic/autologous bone marrow or solid organ transplantation.
- Has current pneumonitis or history of non-infectious pneumonitis that required steroids or other immunosuppressive agents.
- Recent history (within the past 6 months) of uncontrolled symptomatic ascites, pleural or pericardial effusions .
- Recent history (within the past 6 months) of gastrointestinal obstruction that required surgery, acute diverticulitis, inflammatory bowel disease, or intra-abdominal abscess.
- Recent history of allergen desensitization therapy within 4 weeks of randomization.
- History or evidence of cardiac abnormalities within the 6 months prior to randomization which include.
- Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
- Active infection requiring systemic therapy.
- Known human immunodeficiency virus (HIV) infection, or positive test for hepatitis B active infection (presence of hepatitis B surface antigen), or hepatitis C active infection.
- History of severe hypersensitivity to monoclonal antibodies or to the chemotherapies under investigation including any ingredient used in the formulation.
- Known history of active tuberculosis.
- Any serious and/or unstable pre-existing medical condition (aside from malignancy).
- Any psychiatric disorder, or other condition that could interfere with participant's safety, obtaining informed consent, or compliance to the study procedures in the opinion of the investigator.
- 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 date of randomization.

Schema di trattamento: 

- GSK3359609/pembrolizumab/carboplatino o cisplatino/5Fu, o
- Placebo/pembrolizumab/carboplatino o cisplatino /5Fu (per 4-6 cicli)

poi lo studio continuerà con infusioni di:

- GSK3359609-Pembrolizumab
- Placebo-Pembrolizumab

Trattamento sperimentale: 

- GSK3359609
- Pembrolizumab
- Platinum based chemotherapy
- Fluorouracil (5FU

Trattamento di controllo: 

- Placebo
- Pembrolizumab
- Platinum based chemotherapy
- Fluorouracil (5FU)

Obiettivi primari dello studio: 

1. Overall Survival (OS) in total population.
2. OS in programmed death receptor-ligand 1 (PD-L1) combined positive score (CPS) >=1 population
3. Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 in total population

Obiettivi secondari dello studio: 

- PFS per RECIST v1.1 in the PD-L1 CPS >=1 population [ Time Frame: Up to 48 months ]
    PFS per RECIST v1.1 in the PD-L1 CPS >= 1, defined as the time from the date of randomization until the date of disease progression or death due to any cause, whichever comes first

- Milestone OS rate at 12, 24 and 36 months in total population [ Time Frame: Months 12, 24 and 36 ]
    Milestone OS rate at 12, 24, and 36 months will be evaluated from survival curves.

- Milestone OS rate at 12, 24 and 36 months in PD-L1 CPS >=1 population [ Time Frame: Months 12, 24 and 36 ]
    Milestone OS rate at 12, 24, and 36 months will be evaluated from survival curves.

- Overall Response Rate (ORR) per RECIST v1.1 in total population [ Time Frame: Up to 66 months ]
    ORR is defined as the proportion of the participants who have a complete response (CR) or partial response (PR) as the best overall response per RECIST v1.1.

- ORR per RECIST v1.1 in PD-L1 CPS >=1 population [ Time Frame: Up to 66 months ]
    ORR is defined as the proportion of the participants who have a CR or PR as the best overall response per RECIST v1.1.

- Disease Control Rate (DCR) per RECIST v1.1 in total population [ Time Frame: Up to 66 months ]
    DCR is defined as the percentage of participants with a best overall response of CR or PR at any time plus stable disease (SD) meeting the minimum time of 18 weeks per RECIST v1.1.

- DCR per RECIST v1.1 in PD-L1 CPS >=1 population [ Time Frame: Up to 66 months ]
    DCR is defined as the percentage of participants with a best overall response of CR or PR at any time SD meeting the minimum time of 18 weeks per RECIST v1.1.

- Duration of Response (DoR) per RECIST v1.1 in total population [ Time Frame: Up to 66 months ]
    DoR is defined as the time from first documented evidence of CR or PR until first documented disease progression per RECIST v1.1, whichever occurs first, among participants who demonstrated CR or PR as the best overall response per RECIST v1.1.

- DoR per RECIST v1.1 in PD-L1 CPS >=1 population [ Time Frame: Up to 66 months ]
    DoR is defined as the time from first documented evidence of CR or PR until first documented disease progression per RECIST v1.1, whichever occurs first, among participants who demonstrated CR or PR as the best overall response per RECIST v1.1.

- Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) in total population [ Time Frame: Up to 66 months ]
    Number of participants with any AEs and SAEs per International Council on Harmonization (ICH) definitions.

- Number of participants with adverse Events of Special Interest (AESI) in total population [ Time Frame: Up to 66 months ]
    AESI are defined as events of potential immunologic etiology, including immune-related (ir) AEs

- Number of participants with AEs and SAEs in PD-L1 CPS>=1 population [ Time Frame: Up to 66 months ]
    Number of participants with any AEs and SAEs per ICH definitions.

- Number of participants with AESIs in PD-L1 CPS>=1 population [ Time Frame: Up to 66 months ]
    AESI are defined as events of potential immunologic etiology, including irAEs

- Severity of AEs and SAEs in total population [ Time Frame: Up to 66 months ]
    Severity for each AE and SAE will be reported during the study and will assign a grade according to the National Cancer Institute - Common Toxicity Criteria for Adverse Events (NCI-CTCAE) v5.0

- Severity of AESIs in total population [ Time Frame: Up to 66 months ]
    Severity for each AESIs will be reported during the study and will assign a grade according to the NCI-CTCAE v5.0

- Severity of AEs and SAEs in PD-L1 CPS>=1 population [ Time Frame: Up to 66 months ]
    Severity for each AE and SAE will be reported during the study and will assign a grade according to the NCI-CTCAE v5.0

- Severity of AESI in PD-L1 CPS>=1 population [ Time Frame: Up to 66 months ]
    Severity for each AESI will be reported during the study and will assign a grade according to the NCI-CTCAE v5.0

- Number of participants with dose modifications in total population [ Time Frame: Up to 66 months ]
    Number of participants with dose modifications (i.e. interruptions, discontinuations) in the total populations will be reported

- Number of participants with dose modifications in PD-L1 CPS>=1 population [ Time Frame: Up to 66 months ]
    Number of participants with dose modifications (i.e. interruptions, discontinuations) in the PD-L1 CPS>=1 population will be reported.

- Time to deterioration in pain in total populations [ Time Frame: Up to 66 months ]
    Time to deterioration in pain is defined as the time from the date of randomization to the date of first definitive meaningful deterioration in score measured by structured participants questionnaire.

- Time to deterioration in pain in PD-L1 CPS >=1 populations [ Time Frame: Up to 66 months ]
    Time to deterioration in pain is defined as the time from the date of randomization to the date of first definitive meaningful deterioration in score measured by structured participants questionnaire.

- Time to deterioration in physical function in total population [ Time Frame: Up to 66 months ]
    The time to deterioration in physical function will be measured by the participant-reported outcomes measurement.

- Time to deterioration in physical function in PD-L1 CPS >=1 population [ Time Frame: Up to 66 months ]
    The time to deterioration in physical function will be measured by the participant-reported outcomes measurement.

Data di inizio dell'arruolamento: 13.08.2020

Data di fine dell'arruolamento: 11.03.2024

Centri partecipanti

Nord Italia

Azienda Spedali Civili di Brescia
Piazzale Spedali Civili 1 - 25123 Brescia - BS

Riferimento: Prof. Paolo Bossi
Telefono: 03039951

 

IRCCS Istituto Nazionale dei Tumori
Via Venezian 1 - 20133 Milano - MI

Riferimento: Dr.ssa Lisa Licitra
Telefono: 0223902150
Email: lisa.licitra@istitutotumori.mi.it

 

Ospedale San Raffaele di Milano
Via Olgettina 60 - 20132 Milano - MI
NB: Arruolamento pazienti non ancora attivo

Riferimento: Dr.ssa Vanesa Gregorc
Telefono: 0226436627
Email: gregorc.vanesa@hsr.it

 

A.O.U. Policlinico di Modena
Via del Pozzo 71 - 41100 Modena - MO
NB: Arruolamento pazienti non ancora attivo

Riferimento: Dr.ssa Federica Bertolini
Telefono: 0594223864
Email: bertolini.federica@aou.mo.it

 

Istituto Oncologico Veneto IRCCS
Via Gattamelata 64 - 35128 Padova - PD
NB: Arruolamento pazienti non ancora attivo

Riferimento: Dr.ssa Maria Grazia Ghi
Telefono: 049215931
Email: oncologia2@iov.veneto.it

 

Ospedale San Paolo di Savona ASL 2 Savonese
Via Genova 30 - 17021 Savona - SV

Riferimento: Dr. Benasso Marco
Telefono: 0198404436
Email: m.benasso@asl2.liguria.it

 

Centro Italia

Nuovo Ospedale di Prato
Via Suor Niccolina Infermiera 20 - 59100 Prato - PO
NB: Arruolamento pazienti non ancora attivo

Riferimento: Dr. Giacomo Giulio Baldi
Telefono: 0574802520
Email: giacomogiulio.baldi@uslcentro.toscana.it

 

Istituto Nazionale Tumori “Regina Elena”
Via Elio Chianesi 53 - 00144 Roma - RM
NB: Arruolamento pazienti non ancora attivo

Riferimento: Dr.ssa Consuelo D'Ambrosio
Telefono: 0652666919
Email: consuelo.dambrosio@ifo.gov.it

 

Sud Italia e isole

AO Papardo
Contrada Papardo - 98158 Messina - ME
NB: Arruolamento pazienti non ancora attivo

Riferimento: Prof. Vincenzo Adamo
Email: vadamo@unime.it

 

Istituto Nazionale Tumori IRCCS Fondazione Pascale
Via Mariano Semmola - 80131 Napoli - NA
NB: Arruolamento pazienti non ancora attivo

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2019-003981-42

Data di inserimento: 18.11.2020

Promotore

GlaxoSmithKline

CRO

NA

Principal Investigator ITALIA

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Riferimento: Dr.ssa Lisa Licitra

Telefono: 0223902150

Email: lisa.licitra@istitutotumori.mi.it

Localita: Milano

 

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