NCT06393816

FIRST-NEC (GFPC 01-2022) - Combination of Durvalumab With Etoposide and Platinum

A Multicenter Phase II Study Evaluating the Efficacy and Safety of the Combination of Durvalumab With Etoposide and Platinum as First Line Treatment in Patients With Large-cell Neuroendocrine Carcinomas (LCNECs) of the Lung

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Sponsor: Centre Leon Berard · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The primary objective is to determine the efficacy (Progression-Free Rate at 12 months) of durvalumab combined with etoposide and platinum (either cisplatin or carboplatin) for the first-line treatment of patients with advanced LCNEC confirmed by centralized expert-pathologist review

Detailed description

Large-cell neuroendocrine carcinomas (LCNECs) of the lung are lung tumors (2%) included with small-cell lung cancers (SCLCs) in the subgroup of pulmonary neuroendocrine tumors of high-grade malignancy. Histopathological diagnosis of LCNEC is difficult, with a confirmation rate of only 70-80% after centralized expert-pathologist review. The prognosis of advanced LCNECs is poor, with overall survival (OS) of 8-10 months. The platinum-based regimen is the current recommended first-line treatment for advanced LCNECs in analogy with that given for SCLCs. The previous pivotal GFPC 03-02 trial demonstrated the efficacy of first-line platinum-etoposide in advanced LCNECs with a median Progression-Free Survival (PFS), OS and 1-year PFS of 5 months, 7.7 months and 15% respectively. The GFPC 03-2017 trial has recently reported that 75% of the tumor samples of LCNEC express programmed cell death protein-ligand-1 (PD-L1) in immune infiltrating tumor cells (ICs), and PD-L1 expression on ICs has been previously correlated with clinical efficacy of Immune Checkpoint Inhibitors (ICI) in Non-small Cell Lung Cancer. Numerous retrospective studies have also suggested ICI efficacy against LCNECs with significantly prolonged OS observed in ICI-treated LCNEC patients. Recently, the prospective NIPINEC study results demonstrated second-line nivolumab-ipilimumab efficacy against LCNECs. Moreover, at ESMO 2022, the NICE-NEC prospective phase II study on LCNECs of digestive origin found an impressive efficacy of first-line triplet platinum-etoposide-ICI with a median OS of 13,9 months, and 44 % of long survivor patients (OS\>18 months). Finally, the CASPIAN trial demonstrated the superiority of the combination of durvalumab with platinum-etoposide compared to chemotherapy alone in patients with SCLCs, with an acceptable toxicity profile. Therefore, within the network of GFPC centers, the investigators propose a prospective, multicenter, open-label, phase II study with an external control arm (ESME database), that aims at evaluating the efficacy and safety of the combination of durvalumab with platinum-etoposide chemotherapy as first-line treatment in patients with an advanced LCNECs.

Conditions

• Large Cell Neuroendocrine Carcinoma of the Lung

Interventions

Type	Name	Description
DRUG	Durvalumab with etoposide and Carboplatin/Cisplatin	Combination of durvalumab with etoposide and Carboplatin/Cisplatin as First Line Treatment in Patients With Large-cell Neuroendocrine Carcinomas of the Lung. All patients (either with confirmed diagnosis or not) will be treated and followed-up: * During the induction: every 3 weeks for 12 weeks (4 cycles) * During the maintenance: every 4 weeks for 24 months

Timeline

• Start date: 2024-06-13
• Primary completion: 2028-09-01
• Completion: 2029-09-01
• First posted: 2024-05-01
• Last updated: 2024-08-02

Locations

31 sites across 2 countries: France, Reunion