FIRST-NEC (GFPC 01-2022) - Combination of Durvalumab With Etoposide and Platinum
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorCentre Leon Berard
About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥ 18 years at the time of study entry;
Locally documented histological diagnosis of Large-Cell NeuroEndocrine Carcinoma of the lung (2021 WHO classification of Lung Tumors );
Patient must have sufficient material to achieve central histological confirmation and exploratory analyses (1 representative FFPE block or at least 10 unstained slides);
Setting of the disease: locally advanced (Stage III) not eligible for loco-regional therapy or metastatic (Stage IV) in first line treatment (8th TNM classification).
Disqualifiers
Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study (wash-out period of 28 days);
Patient previously treated for a LCNEC in a metastatic setting;
Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab;
Any concurrent chemotherapy, Investigational product, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable;
Trial design
Design model
Single group
Treatments tested in this trial
Durvalumab with etoposide and Carboplatin/Cisplatin
DrugCombination 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
Treatment groups
80 Participants
are divided into 1 treatment groupGroup A: Experimental : Durvalumab with etoposide and Carboplatin/CisplatinExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
the efficacy (Progression-Free Rate at 12 months) of durvalumab combined with etoposide and platinum (either cisplatin or carboplatin) for the 1st-line treatment of patients with advanced LCNEC confirmed by centralized expert-pathologist review.
The Progression-Free Rate at 12 months (12M-PFR) will be defined as the percentage of patients with a LCNEC confirmed by centralized expert-pathologist review and presenting a complete response (CR), a partial response (PR) or a stable disease (SD) 12 months after the date of treatment start, as per the independent central radiological review committee
Time frame
12 monthsSecondary outcomes
1
12-week Objective Response Rate (ORR)
proportion of patients with a LCNEC confirmed by centralized expert-pathologist review with a complete response (CR) or partial response (PR), 12 weeks after the date of treatment start
Time frame
12 weeks2
12-week Disease Control Rate
proportion of patients with a LCNEC confirmed by centralized expert-pathologist review with a complete response (CR), partial response (PR) or with stable disease (SD), 12 weeks after the date of treatment start
Time frame
12 weeks3
Progression-Free Survival (PFS)
time from the date of first study treatment administration to the date of first documented disease progression (reviewed centrally) or the date of death from any cause. Patients without event at the time of analysis will be censored at the date of their last tumor assessment.
Time frame
From date of the first study treatment administration until the date of first documented radiological progression or date of death from any cause, assessed up to 63 months4
Overall Survival
time from the date of first study treatment administration to the date of death from any cause. Patients still alive at the time of the analysis will be censored at the time they are known to be alive
Time frame
from the date of first study treatment administration to the date of death from any cause, assessed up to 63 monthsOther outcomes
1
Treatment effectiveness of the experimental combination compared to an external control arm
PFS and OS will be compared between experimental arm (durvalumab with platinum-etoposide) and an external control arm from the ESME-AMLC real-world database. This comparison will be performed through combined statistical approach using the emulation of a target trial associated with appropriate statistical adjustment techniques to control for confounding biases and thereby reach causal inference capability. The emulation process will consist of outlining key elements of this target trial protocol and then applying them to the ESME data.
Time frame
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 63 months2
Histopathological diagnosis concordance rate
The proportion of patients with a histopathological diagnosis confirmed by central review will be described. The proportion of patients with a histopathological diagnosis confirmed by central review will be described.
Time frame
Through central histopathological completion, an average of 6 weeks3
12-week Objective Response Rate as a predictive and prognostic factors
The 12W-ORR will be studied as predictive (12M-PFR and ORR) and prognostic factors (OS) of efficacy
Time frame
12 weeks4
Overall Survival in the whole study population
Overall study as usually published in other studies (in which the diagnosis is not confirmed).
Time frame
From the date of first study treatment administration to the date of death from any cause, assessed up to 63 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Centre Leon Berard
Lead sponsor
Groupe Francais De Pneumo-Cancerologie
Collaborator
Source ClinicalTrials.gov