AGNOSTIC THERAPY IN A PHASE II SINGLE-ARM STUDY IN FIRST-LINE TREATMENT OF DURVALUMAB IN ASSOCIATION WITH CARBOPLATIN OR CISPLATIN AND ETOPOSIDE IN PATIENTS AFFECTED BY EXTENSIVE STAGE - EXTRAPULMONARY SMALL CELL CARCINOMA
NCT Number: NCT06464068
Acronym: DURVASCC
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Extrapulmonary Small Cell Carcinoma
Interventions: DRUG: Durvalumab
Sponsor: Gruppo Oncologico Italiano di Ricerca Clinica
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 66
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-01-16
Completion Date: 2028-01-01
Locations: AUSL-IRCCS of Reggio Emilia, Reggio Emilia, 42123, Italy

Summary:
This is a phase II, single-arm, multicenter study to evaluate the activity and safety of durvalumab in combination with carboplatin or cisplatin plus etoposide in patients with treated ES-EPSCC.

Primary Outcome Measures: progression free survival (PFS), To evaluate the preliminary efficacy in terms of 12 months progression free survival (PFS) of durvalumab in association with carboplatin or cisplatin and etoposide in first line patients affected by extensive stage EPSCC. PFS isdefined as the time from initiation of study treatment to the first occurrence of disease progression or death from any cause, whichever occurs first. According to the results of the CASPIAN trial \[18\] in which was observed a 12-month progression-free survival rates of 5% (2.4-8.0) for patients that had received Platinum-etoposide, it is expected to detect an increasing of at least 10 percentage points (to 15%)., 12 months
Secondary Outcome Measures: Objective Response Rate (ORR), Activity of durvalumab in combination with carboplatin or cisplatin plus etoposide in patients with untreated extensive- stage extrapulmonary small cell lung cancer (EPSCC). Activity will be measured as Objective Response Rate (ORR), defined as the percentage of patients who attain complete response (CR) or partial response (PR) according to RECIST v1.1., 12 months|Disease control rate (DCR), Disease control rate (DCR) measured as the percentage of patientswho have archived CR, PR, and stable disease (SD)., 12 months|Overall survival (OS), Overall survival (OS), defined as the time from initiation of study treatment to death from any cause., 24 months|Duration of response (DOR), Duration of response (DOR), is defined as the time from initial response to disease progression or death among patients who have experienced a CR or PR (unconfirmed) during the study. Duration of response will be calculated based on disease status evaluated by the investigator according to RECIST v1.1., 12 months|quality of life (QoL), To describe change in quality of life of patients during the study, measured as pre-defined PRO endpoints in this study are mean change from baseline in questionnaire administred at the enrollment time (baseline) and after the induction phase (3 +/- 2 weeks), 24 months|incidence, nature, frequency, and severity of Adverse Events (AEs), Safety profile of durvalumab, defined in terms of incidence, nature, frequency, and severity of Adverse Events (AEs) and laboratory abnormalities graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0;, 24 months
Other Outcome Measures: biomarkers associated with sensitivity/resistance to immune checkpoint inhibitors, To identify possible biomarkers associated with sensitivity/resistance to immune checkpoint inhibitors, tumor samples from enrolled patients will undergo whole exome sequencing (WES) and gene expression profiling by using a 3' RNA Seq approach.

For all the patients enrolled to investigate the occurrence of genetic alterations that might be associated with acquired resistance to immune checkpoint inhibitors, blood samples will be collected by analyzing the circulating free DNA (cfDNA). To this end, plasma will be collected at baseline, prior to cycle 5, and at the end of treatment (progression of disease). The cfDNA will be analyzed by targeted sequencing panels., 24 months