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 treated by durvalumab every 4 weeks. DURVALUNG study aims to evaluate the activity of durvalumab maintenance treatment in frail LD-SCLC patients who have not progressed following platinum-based concomitant or sequential CRT.
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 activity of durvalumab maintenance treatment in frail LD-SCLC patients who have not progressed following platinum-based concomitant or sequential CRT.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
100
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 will receive durvalumab intravenously 1500 mg every 4 weeks until disease progression, unacceptable toxicity, death or patient's decision for a maximum of 24 months.
Centre de Radiothérapie du Pays d'Aix
Aix-en-Provence, France
Centre Hospitalier du Pays d'Aix
Aix-en-Provence, France
Institut du Cancer Avignon-Provence
Avignon, France
Centre d'Oncologie du Pays Basque
Bayonne, France
CH de la côte Basque
Bayonne, France
Clinique Belharra
Bayonne, France
Centre François Baclesse
Caen, France
CHU de CAEN
Caen, France
Centre Jean Perrin
Clermont-Ferrand, France
CHI Créteil
Créteil, France
...and 22 more locations
Progression-free survival
The progression-free survival (PFS) is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.
Time frame: From inclusion to disease progression or death, up to 3.5 years
Overall survival
The overall survival (OS) is the length of time from randomization that patients enrolled in the study are still alive.
Time frame: From inclusion to death, up to 3.5 years
Occurrence of adverse events coded using NCI CTC-AE version 5.0.(Safety )
Occurrence of adverse events coded using NCI CTC-AE version 5.0. The National Cancer Institute-Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5) is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale, divided into 5 grades (1 = "mild", 2 = "moderate", 3 = "severe", 4 = "life-threatening", and 5 = "death") determined by the investigator, will make it possible to assess the severity of the disorders.
Time frame: Throughout study completion, up to 4 years
Quality of life questionnaire - Core 30 (QLQ-C30)
Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials. The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.
Time frame: At inclusion before treatment start and every 4 weeks for the first year from inclusion and then every 12 weeks until end of treatment or death, up to 2 years
Quality of life questionnaire - Lung cancer module (QLQ-LC13)
The QLQ-LC13 contains 13 items to assess both multi-item and single-item measures of lung cancer-associated symptoms (coughing, haemoptysis, dyspnoea, and pain) and side-effects from conventional chemo- and radiotherapy (hair loss, neuropathy, sore mouth, and dysphagia). All items are rated on a four-point Likert-type scale (1 = "not at all", 2 = "a little", 3 = "quite a bit", and 4 = "very much).
Time frame: At inclusion before treatment start and every 4 weeks for the first year from randomization and then every 12 weeks until end of treatment or death, up to 2 years
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