This thesis is based on the internship experience at the CTO-OH (Clinical Trial Office-OncoHematologic) of the IRCCS Policlinico San Matteo Foundation in Pavia. Throughout the internship period, I gained practical skills in clinical trial management, from patient data collection to organizing visits, adhering to Good Clinical Practice (GCP) regulations for experimental drug studies. The thesis aims to contribute to the understanding of the clinical research world and the processes involved in conducting a clinical trial. Specifically, it will provide a comprehensive description of the Phase II clinical trial, single-arm, open-label, multicenter named DEDALUS, promoted by IRCCS Policlinico San Matteo. This study aims to evaluate the efficacy of a new therapeutic regimen for unresectable stage III non-small cell lung cancer, with a sequential combination of chemo-immunotherapy and low-dose hypofractionated thoracic radiotherapy, followed by maintenance treatment with the drug Durvalumab. The DEDALUS study protocol is based on the positive results of the PACIFIC clinical trial, which demonstrated the efficacy of Durvalumab as maintenance therapy after concurrent radio-chemotherapy in patients with advanced non-small cell lung cancer. This choice was driven by the identified unmet medical need in daily clinical practice. Initially, an overview of stage III lung cancer and the drug Durvalumab will be provided, with a focus on the results of the PACIFIC study. Subsequently, an analysis of the DEDALUS clinical trial protocol will be presented, including a description of its rationale, objectives, and methodology. The processes related to the planning, conduct, and management of a clinical trial will be examined, with particular attention to documentation for submission, data and experimental drug management, and an in-depth exploration of the crucial aspect of pharmacovigilance. Finally, the current status of the DEDALUS study will be described, highlighting the innovations introduced in protocol 2.1 and outlining future perspectives and objectives that the study aims to achieve. The importance of continuing research and development of innovative therapies to improve the clinical outcome of patients with stage III non-small cell lung cancer will be emphasized.
La presente tesi si basa sull'esperienza di stage presso il CTO-OH (clinical trial office-oncohematologic) della Fondazione IRCCS Policlinico San Matteo di Pavia. Durante il periodo di tirocinio, ho acquisito competenze pratiche nella gestione dei trial clinici, dalla raccolta dei dati dei pazienti all'organizzazione delle visite, seguendo le normative delle Good Clinical Practice (GCP ) per lo studio di farmaci sperimentali. La tesi si propone di fornire un contributo alla comprensione del mondo della ricerca clinica e dei processi coinvolti nella conduzione di uno studio clinico. In particolare, si darà un'ampia descrizione dello studio clinico di fase II, a braccio singolo, in aperto, multicentrico denominato DEDALUS, promosso dall'IRCCS Policlinico San Matteo. Questo studio mira a valutare l'efficacia di un nuovo regime terapeutico per il tumore al polmone non a piccole cellule di stadio III non resecabile, con una combinazione sequenziale di chemio-immunoterapia e radioterapia toracica ipo-frazionata a bassa dose, seguita da un trattamento di mantenimento con il farmaco Durvalumab. Il protocollo dello studio DEDALUS si basa sui risultati positivi dello studio clinico PACIFIC, che ha dimostrato l'efficacia di Durvalumab come terapia di mantenimento dopo il trattamento radio-chemioterapico concomitante nei pazienti affetti da tumore al polmone non a piccole cellule in fase avanzata. Questa scelta è stata guidata dalla necessità medica non soddisfatta identificata nella pratica clinica quotidiana. Si fornirà inizialmente una panoramica sul tumore al polmone di stadio III e sul farmaco Durvalumab, con un focus sui risultati dello studio PACIFIC. Successivamente, verrà presentata un'analisi del protocollo dello studio clinico DEDALUS, includendo una descrizione del suo razionale, degli obiettivi e della metodologia utilizzata. Si esamineranno i processi relativi alla pianificazione, conduzione e gestione di uno studio clinico, con particolare attenzione alla documentazione per la sottomissione, alla gestione dei dati e del farmaco sperimentale, oltre a un approfondimento sull'importante aspetto della farmacovigilanza. Infine, si descriverà lo stato attuale dello studio DEDALUS, presentando le novità introdotte nel protocollo 2.1 e delineando le prospettive future e gli obiettivi che lo studio si prefigge di raggiungere. Si sottolineerà l'importanza di continuare la ricerca e lo sviluppo di terapie innovative per migliorare l'esito clinico dei pazienti affetti da carcinoma polmonare non a piccole cellule allo stadio III.
"La gestione della sperimentazione dello studio di fase II, multicentrico, in aperto, DEDALUS, promosso dalla Fondazione IRCCS Policlinico San Matteo presso l'Onco-Hematologic Clinical Trial Office."
DERIU, EMILIA
2022/2023
Abstract
This thesis is based on the internship experience at the CTO-OH (Clinical Trial Office-OncoHematologic) of the IRCCS Policlinico San Matteo Foundation in Pavia. Throughout the internship period, I gained practical skills in clinical trial management, from patient data collection to organizing visits, adhering to Good Clinical Practice (GCP) regulations for experimental drug studies. The thesis aims to contribute to the understanding of the clinical research world and the processes involved in conducting a clinical trial. Specifically, it will provide a comprehensive description of the Phase II clinical trial, single-arm, open-label, multicenter named DEDALUS, promoted by IRCCS Policlinico San Matteo. This study aims to evaluate the efficacy of a new therapeutic regimen for unresectable stage III non-small cell lung cancer, with a sequential combination of chemo-immunotherapy and low-dose hypofractionated thoracic radiotherapy, followed by maintenance treatment with the drug Durvalumab. The DEDALUS study protocol is based on the positive results of the PACIFIC clinical trial, which demonstrated the efficacy of Durvalumab as maintenance therapy after concurrent radio-chemotherapy in patients with advanced non-small cell lung cancer. This choice was driven by the identified unmet medical need in daily clinical practice. Initially, an overview of stage III lung cancer and the drug Durvalumab will be provided, with a focus on the results of the PACIFIC study. Subsequently, an analysis of the DEDALUS clinical trial protocol will be presented, including a description of its rationale, objectives, and methodology. The processes related to the planning, conduct, and management of a clinical trial will be examined, with particular attention to documentation for submission, data and experimental drug management, and an in-depth exploration of the crucial aspect of pharmacovigilance. Finally, the current status of the DEDALUS study will be described, highlighting the innovations introduced in protocol 2.1 and outlining future perspectives and objectives that the study aims to achieve. The importance of continuing research and development of innovative therapies to improve the clinical outcome of patients with stage III non-small cell lung cancer will be emphasized.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/16967