Durvalumab Maintenance After Thoracic Chemoradiotherapy in Frail Small Cell Lung Cancer Patients Whose Disease is Limited to the Thorax — DURVALUNG  

Small Cell Lung Carcinoma Clinical Trial

Official title: A Phase II Study of Durvalumab (MEDI 4736) Maintenance in Frail Limited Disease Small Cell Lung Cancer Patients After Thoracic Chemoradiotherapy (CRT)

Status Recruiting

Clinical Trial Summary

This study is an academic-lead, open-label, multicenter, randomized phase II trial for frail limited disease Small Cell Lung Cancer (LD-SCLC) patients.

Frail conditions are: Eastern Cooperative Oncology Group performance status (ECOG PS) 2 or ECOG PS 0-1 and older than 70 or ECOG PS 0-1 and did not receive a concomitant thoracic chemo-radiotherapy (CRT) because of comorbidities.

During the screening phase, patients complete either the standard concomitant or sequential thoracic CRT and cisplatin-etoposide regimen or carboplatin AUC5 to AUC6 etoposide regimen.

Patients showing a disease control (defined as stable disease [SD], partial response [PR], or complete response [CR] according to RECIST v1.1) at the radiological evaluation performed after the end of thoracic CRT can receive prophylactic cranial irradiation (PCI) as per local practice. They will then be randomized to receive durvalumab every 4 weeks (experimental arm A) or surveillance (control arm B) as per standard of care.

Thus, DURVALUNG study aims to evaluate the efficacy of durvalumab maintenance treatment in frail LD-SCLC patients who have not progressed following platinum-based concomitant or sequential CRT.

Clinical Trial Description

Small Cell Lung Cancer (SCLC) is a rare tumor, accounting nowadays for 10-15% of all new lung cancer diagnosis. Approximately one third of patients present with limited disease (LD-SCLC) confined to the chest with a median survival from 18 to 24 months and a 5-year survival rate between 20% and 25%. A platinum-based chemotherapy combined with etoposide and a concurrent thoracic radiotherapy represents the standard of care for LD-SCLC treatment with a median PFS of 12 months. However, sequential radiotherapy may be preferable for patients with poor performance status or having comorbidity predisposing to a worst tolerability. Clinical evidence supports the immunogenicity of SCLC and the involvement of immune activity in SCLC development and prognosis.

Several immune checkpoint inhibitors got the approbation in first and further lines for the advanced SCLC in the last decade. The most important results have been achieved in the first-line setting for patients receiving a combination of platinum - etoposide chemotherapy and an anti-PD1/PDL-1 inhibitor compared to chemotherapy alone. However, despite these were the first positive results after a while in this setting, the modest absolute benefit showed (3 months) have to be taking into account. The possibility to enhance the immunotherapy efficacy in SCLC field with the radiotherapy administered as part of the standard treatment for a LD-SCLC seems to be a great opportunity. In the PACIFIC trial, the sequential administration of durvalumab in patients with locally advanced, unresectable, stage III Non-Small-Cell Lung Cancer (NSCLC) whose disease had not progressed following platinum-based concurrent thoracic CRT showed a dramatic overall survival improvement compared to placebo, with manageable toxicities. The ADRIATIC phase III trial, is currently recruiting LD-SCLC patients not progressing after the concomitant CRT (NCT03703297). Patients are randomized to receive durvalumab, durvalumab plus tremelimumab or placebo as maintenance treatment. In this trial, only ECOG PS 0-1 patients able to receive a concomitant CRT are eligible. However, in our clinical practice, LD-SCLC patients may not respect these criteria due to the aggressiveness of cancer and comorbidities.

Thus, DURVALUNG study aims to evaluate the efficacy of durvalumab maintenance treatment in frail LD-SCLC patients who have not progressed following platinum-based concomitant or sequential CRT. ;

Related Conditions & MeSH terms

• Small Cell Lung Carcinoma

• NCT number: NCT05617963
• Study type: Interventional
• Source: UNICANCER
• Contact: Clotilde SIMON
• Phone: +33 (0) 1 73 79 79 11
• Email: c-simon@unicancer.fr
• Status: Recruiting
• Phase: Phase 2
• Start date: March 24, 2023
• Completion date: March 30, 2029