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Clinical Trial Protocol

A phase II, open-label, single-arm trial of carboplatin plus etoposide with bevacizumab and atezolizumab in patients with extended-stage small-cell lung cancer (CeLEBrATE study): background, design and rationale

    Elisa Andrini

    Department of Experimental, Diagnostic & Specialty Medicine (DIMES), University of Bologna, Bologna 40138, Italy

    ,
    Giuseppe Lamberti

    *Author for correspondence: Tel.: +39 051 214 2204;

    E-mail Address: giuseppe.lamberti8@unibo.it

    Department of Experimental, Diagnostic & Specialty Medicine (DIMES), University of Bologna, Bologna 40138, Italy

    Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy

    ,
    Francesca Mazzoni

    Medical Oncology Unit, University Hospital Careggi, Firenze 50134, Italy

    ,
    Ferdinando Riccardi

    Oncology Unit - AORN Cardarelli, Naples 80131, Italy

    ,
    Andrea Bonetti

    Department of Oncology, Mater Salutis Hospital, Legnago 37045, Italy

    ,
    Alessandro Follador

    Department of Oncology, University Hospital Santa Maria Della Misericordia, Udine 33100, Italy

    ,
    Fabrizio Artioli

    Oncology & Palliative Care Units, Civil Hospital Carpi, USL, Carpi 41012, Italy

    ,
    Carlo Genova

    Academic Oncology Unit, IRCCS Ospedale Policlinico San Martino, Genoa 16132, Italy

    Department of Internal Medicine & Medical Specialties (DiMI), Università degli Studi di Genova, Genoa 16132, Italy

    ,
    Fausto Barbieri

    Division of Medical Oncology, Azienda Ospedaliero-Universitaria Policlinico, Modena 41125, Italy

    ,
    Antonio Frassoldati

    Department of Oncology, Azienda Ospedaliero Universitaria di Ferrara-Arcispedale Sant'Anna, Ferrara 44124, Italy

    ,
    Matteo Brighenti

    Medical Oncology Department, ASST Cremona, Cremona 26100, Italy

    ,
    Ida Colantonio

    Medical Oncology Unit, Hospital of Cuneo, Cuneo 12100, Italy

    ,
    Giulia Pasello

    Department of Surgery, Oncology & Gastroenterology, University of Padova, Padova 35122, Italy

    Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padova 35122, Italy

    ,
    Corrado Ficorella

    Department of Biotechnological & Applied Clinical Sciences, St Salvatore Hospital, University of L'Aquila, L'Aquila 67100, Italy

    ,
    Saverio Cinieri

    Department of Oncology, Medical Oncology & Breast Unit, Antonio Perrino Hospital, Brindisi 72100, Italy

    ,
    Marcello Tiseo

    Department of Medicine & Surgery, University of Parma & Medical Oncology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma 43126, Italy

    ,
    Francesco Gelsomino

    Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy

    ,
    Michele Tognetto

    Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy

    ,
    Karim Rihawi

    Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy

    &
    Andrea Ardizzoni

    Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy

    Published Online:https://doi.org/10.2217/fon-2021-1027

    Based on improved survival from the addition of PD-L1 inhibitors in phase III trials, the combination of immunotherapy and platinum-doublet chemotherapy has become the new standard treatment for extended-stage small-cell lung cancer (ES-SCLC). Furthermore, the antiangiogenetic agent bevacizumab showed a longer progression-free survival by targeting VEGF that has pleiotropic effects, including immunosuppressive ones. We, therefore, hypothesized that targeting angiogenesis would improve the efficacy of chemoimmunotherapy. The CeLEBrATE trial is an open-label, multicenter, phase II study designed to assess the efficacy and safety of the combination of carboplatin and etoposide plus bevacizumab and atezolizumab in treatment-naive patients with ES-SCLC. The primary end point is overall survival rate at 1 year, while secondary end points include overall response rate, progression-free survival and toxicity.

    Lay abstract

    Extended-stage small-cell lung cancer (ES-SCLC) is a highly aggressive lung cancer subtype, accounting for 13–15% of all lung cancers. For several years, the standard treatment for this disease was based on polychemotherapy, with a rapid disease response but with an equally rapid disease progression. The new standard treatment has recently been changed, based on the results of two large clinical trials, which showed the efficacy and safety of the combination of chemotherapy with immunotherapy compared to chemotherapy alone. Nevertheless, prognosis of ES-SCLC remains poor, and new treatment strategies are urgently needed. Therefore, we designed the CeLEBrATE trial to investigate whether the combination of chemotherapy with antiangiogenetic therapy and immunotherapy is safe and could improve survival in patients with ES-SCLC.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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