Randomised phase II trial of CAPTEM or FOLFIRI as SEcond-line therapy in NEuroendocrine CArcinomas and exploratory analysis of predictive role of PET/CT imaging and biological markers (SENECA trial): a study protocol
Introduction Patients with metastatic or locally advanced, non-resectable, grade 3 poorly differentiated gastroenteropancreatic (GEP) and lung neuroendocrine carcinomas (NECs) are usually treated with in first-line platinum compounds. There is no standard second-line treatment on progression. Accura...
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2020-07-01
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| author | Ivan Lolli Daniele Santini Rossana Berardi Giuseppe Badalamenti Toni Ibrahim Alfredo Berruti Alberto Bongiovanni Chiara Liverani Sara Pusceddu Silvana Leo Giovanni Di Meglio Stefano Tamberi Fabio Gelsomino Francesca Pucci Francesca Bergamo Sergio Ricci Flavia Foca Stefano Severi Mauro Cives Davide Campana Nicola Silvestris Angela Buonadonna Maria Pia Brizzi Francesca Spada Sara Cingarlini Lorenzo Antonuzzo Davide Pastorelli |
| author_facet | Ivan Lolli Daniele Santini Rossana Berardi Giuseppe Badalamenti Toni Ibrahim Alfredo Berruti Alberto Bongiovanni Chiara Liverani Sara Pusceddu Silvana Leo Giovanni Di Meglio Stefano Tamberi Fabio Gelsomino Francesca Pucci Francesca Bergamo Sergio Ricci Flavia Foca Stefano Severi Mauro Cives Davide Campana Nicola Silvestris Angela Buonadonna Maria Pia Brizzi Francesca Spada Sara Cingarlini Lorenzo Antonuzzo Davide Pastorelli |
| author_sort | Ivan Lolli |
| collection | DOAJ |
| description | Introduction Patients with metastatic or locally advanced, non-resectable, grade 3 poorly differentiated gastroenteropancreatic (GEP) and lung neuroendocrine carcinomas (NECs) are usually treated with in first-line platinum compounds. There is no standard second-line treatment on progression. Accurate biomarkers are needed to facilitate diagnosis and prognostic assessment of patients with NEC.Methods and analysis The SEcond-line therapy in NEuroendocrine CArcinomas (SENECA) study is a randomised, non-comparative, multicentre phase II trial designed to evaluate the efficacy and safety of folinic acid, 5-fluorouracil and irinotecan (FOLFIRI) or capecitabine plus temozolomide (CAPTEM) regimens after failure of first-line chemotherapy in patients with lung NEC and GEP-NEC. Secondary aims are to correlate the serum miRNA profile and primary mutational status of MEN1, DAXX, ATRX and RB-1 with prognosis and outcome and to investigate the prognostic and predictive role of the Ki-67 score and 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) or 68Ga-PET/CT. The main eligibility criteria are age ≥18 years; metastatic or locally advanced, non-resectable, grade 3 lung or GEP-NECs; progression to first-line platinum-based chemotherapy. A Bryant and Day design taking into account treatment activity and toxicity was used to estimate the sample size. All analyses will be performed separately for each treatment group in the intention-to-treat population. A total of 112 patients (56/arm) will be randomly assigned (1:1) to receive FOLFIRI every 14 days or CAPTEM every 28 days until disease progression or unacceptable toxicity or for a maximum of 6 months. Patients undergo testing for specific biomarkers in primary tumour tissue and for miRNA in blood samples. MiRNA profiling will be performed in the first 20 patients who agree to participate in the biological substudy.Ethics and dissemination The SENECA trial, supported by Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), was authorised by the locals Ethics Committee and the Italian Medicines Agency (AIFA). Results will be widely disseminated via peer-reviewed manuscripts, conference presentations and reports to relevant authorities.The study is currently open in Italy.Trail registration number NCT03387592; Pre-results. EudraCT-2016-000767-17.Protocol version Clinical Study Protocol Version 1, 7 November 2016. |
| format | Article |
| id | doaj-art-1bee21f43655476bb6cd7b2b5d64ca29 |
| institution | OA Journals |
| issn | 2044-6055 |
| language | English |
| publishDate | 2020-07-01 |
| publisher | BMJ Publishing Group |
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| series | BMJ Open |
| spelling | doaj-art-1bee21f43655476bb6cd7b2b5d64ca292025-08-20T02:19:27ZengBMJ Publishing GroupBMJ Open2044-60552020-07-0110710.1136/bmjopen-2019-034393Randomised phase II trial of CAPTEM or FOLFIRI as SEcond-line therapy in NEuroendocrine CArcinomas and exploratory analysis of predictive role of PET/CT imaging and biological markers (SENECA trial): a study protocolIvan Lolli0Daniele Santini1Rossana Berardi2Giuseppe BadalamentiToni Ibrahim3Alfredo BerrutiAlberto Bongiovanni4Chiara Liverani5Sara Pusceddu6Silvana Leo7Giovanni Di Meglio8Stefano Tamberi9Fabio Gelsomino10Francesca Pucci11Francesca Bergamo12Sergio Ricci13Flavia Foca14Stefano Severi15Mauro CivesDavide CampanaNicola SilvestrisAngela Buonadonna16Maria Pia BrizziFrancesca Spada17Sara Cingarlini18Lorenzo Antonuzzo19Davide PastorelliDepartment of Oncology, Istituto Nazionale di Ricovero e Cura a Carattere Scientifico Saverio de Bellis, Castellana Grotte, Puglia, ItalyUOC Oncologia Medica A, Policlinico Umberto 1, Università degli Studi di Roma La Sapienza, Rome, ItalyOncology Clinic, AOU delle Marche, Ancona, ItalyOsteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, ItalyOsteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, ItalyOsteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, ItalyDepartment of Medical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Lombardia, ItalyOncology Unit, Ospedale Vito Fazzi, Lecce, Puglia, ItalyOncology Unit, Ospedale di Bolzano, Bolzano, Trentino-Alto Adige, ItalyOncology Unit, Ospedale degli Infermi di Faenza, Faenza, Emilia-Romagna, ItalyDepartment of Oncology and Hematology, University Hospital Modena, Modena, ItalyMedical Oncology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Emilia-Romagna, ItalyMedical Oncology 1, Istituto Oncologico Veneto IOV-IRCSS, Padua, ItalyInternal Medicine and Medical Oncology, Santa Chiara Hospital, Pisa, Toscana, ItalyUnit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, ItalyNuclear Medicine Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, ItalyUnit of Medical Oncology and Cancer Prevention, Centro di Riferimento Oncologico di Aviano IRCCS, Aviano, ItalyDivision of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, IEO IRCCS, European Institute of Oncology, Milano, ItalyThe Pancreas Institute, University and Hospital Trust of Verona, Verona, ItalyClinical Oncology Unit, University Hospital Careggi, Firenze, ItalyIntroduction Patients with metastatic or locally advanced, non-resectable, grade 3 poorly differentiated gastroenteropancreatic (GEP) and lung neuroendocrine carcinomas (NECs) are usually treated with in first-line platinum compounds. There is no standard second-line treatment on progression. Accurate biomarkers are needed to facilitate diagnosis and prognostic assessment of patients with NEC.Methods and analysis The SEcond-line therapy in NEuroendocrine CArcinomas (SENECA) study is a randomised, non-comparative, multicentre phase II trial designed to evaluate the efficacy and safety of folinic acid, 5-fluorouracil and irinotecan (FOLFIRI) or capecitabine plus temozolomide (CAPTEM) regimens after failure of first-line chemotherapy in patients with lung NEC and GEP-NEC. Secondary aims are to correlate the serum miRNA profile and primary mutational status of MEN1, DAXX, ATRX and RB-1 with prognosis and outcome and to investigate the prognostic and predictive role of the Ki-67 score and 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) or 68Ga-PET/CT. The main eligibility criteria are age ≥18 years; metastatic or locally advanced, non-resectable, grade 3 lung or GEP-NECs; progression to first-line platinum-based chemotherapy. A Bryant and Day design taking into account treatment activity and toxicity was used to estimate the sample size. All analyses will be performed separately for each treatment group in the intention-to-treat population. A total of 112 patients (56/arm) will be randomly assigned (1:1) to receive FOLFIRI every 14 days or CAPTEM every 28 days until disease progression or unacceptable toxicity or for a maximum of 6 months. Patients undergo testing for specific biomarkers in primary tumour tissue and for miRNA in blood samples. MiRNA profiling will be performed in the first 20 patients who agree to participate in the biological substudy.Ethics and dissemination The SENECA trial, supported by Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), was authorised by the locals Ethics Committee and the Italian Medicines Agency (AIFA). Results will be widely disseminated via peer-reviewed manuscripts, conference presentations and reports to relevant authorities.The study is currently open in Italy.Trail registration number NCT03387592; Pre-results. EudraCT-2016-000767-17.Protocol version Clinical Study Protocol Version 1, 7 November 2016.https://bmjopen.bmj.com/content/10/7/e034393.full |
| spellingShingle | Ivan Lolli Daniele Santini Rossana Berardi Giuseppe Badalamenti Toni Ibrahim Alfredo Berruti Alberto Bongiovanni Chiara Liverani Sara Pusceddu Silvana Leo Giovanni Di Meglio Stefano Tamberi Fabio Gelsomino Francesca Pucci Francesca Bergamo Sergio Ricci Flavia Foca Stefano Severi Mauro Cives Davide Campana Nicola Silvestris Angela Buonadonna Maria Pia Brizzi Francesca Spada Sara Cingarlini Lorenzo Antonuzzo Davide Pastorelli Randomised phase II trial of CAPTEM or FOLFIRI as SEcond-line therapy in NEuroendocrine CArcinomas and exploratory analysis of predictive role of PET/CT imaging and biological markers (SENECA trial): a study protocol BMJ Open |
| title | Randomised phase II trial of CAPTEM or FOLFIRI as SEcond-line therapy in NEuroendocrine CArcinomas and exploratory analysis of predictive role of PET/CT imaging and biological markers (SENECA trial): a study protocol |
| title_full | Randomised phase II trial of CAPTEM or FOLFIRI as SEcond-line therapy in NEuroendocrine CArcinomas and exploratory analysis of predictive role of PET/CT imaging and biological markers (SENECA trial): a study protocol |
| title_fullStr | Randomised phase II trial of CAPTEM or FOLFIRI as SEcond-line therapy in NEuroendocrine CArcinomas and exploratory analysis of predictive role of PET/CT imaging and biological markers (SENECA trial): a study protocol |
| title_full_unstemmed | Randomised phase II trial of CAPTEM or FOLFIRI as SEcond-line therapy in NEuroendocrine CArcinomas and exploratory analysis of predictive role of PET/CT imaging and biological markers (SENECA trial): a study protocol |
| title_short | Randomised phase II trial of CAPTEM or FOLFIRI as SEcond-line therapy in NEuroendocrine CArcinomas and exploratory analysis of predictive role of PET/CT imaging and biological markers (SENECA trial): a study protocol |
| title_sort | randomised phase ii trial of captem or folfiri as second line therapy in neuroendocrine carcinomas and exploratory analysis of predictive role of pet ct imaging and biological markers seneca trial a study protocol |
| url | https://bmjopen.bmj.com/content/10/7/e034393.full |
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