Trial Title:
A French Real-life Study: EvaluatioN of durvALumab Utilization and Effectiveness for First Line Extensive Stage Small Cell Lung Cancer.
NCT ID:
NCT05683977
Condition:
Small Cell Lung Carcinoma
Conditions: Official terms:
Small Cell Lung Carcinoma
Durvalumab
Study type:
Observational
Overall status:
Active, not recruiting
Study design:
Time perspective:
Prospective
Intervention:
Intervention type:
Drug
Intervention name:
durvalumab
Description:
Visits will be completed at W0 (durvalumab in combination with chemotherapy initiation)
and at regular visits approximately every 6 weeks during the induction period (durvalumab
+ PE) (W6 and W12), then every two months during the maintenance period (durvalumab
alone) for the first year and every three months up to the end of follow-up or the final
visit at M36.
Summary:
Small cell lung cancer (SCLC), characterized by rapid proliferation, high growth fraction
and early development of metastases, is the most aggressive form of lung cancer. In 2021,
an estimated 2.3 million people around the world are diagnosed with lung cancer. In
France, in 2018, with 46 363 new cases and 33 117 deaths, lung cancer represented the
second most common cancer and the first cause of death from cancer. Among those, SCLC
represented 10,8% of all new lung diagnosis, and about two thirds presented at the
extensive stage (ES-SCLC).
Since last three decades, standard treatment in ES-SCLC is based on combination
chemotherapy with a platinum agent and etoposide in first-line with or without concurrent
radiation therapy. Then, the second-line of treatment is topotecan, with few results in
terms of response rates and survival rate. However, the emergence of immune checkpoint
inhibitors targeting the programmed cell death receptor-1 (PD-1)/PD-ligand 1 (PD-L1)
pathway, having an important role in immune regulation became an alternative method in
the management and care of disease. Indeed, recent studies have shown an overall survival
(OS) benefit for patients with ES-SCLC treated in first line with a combination of
platinum-etoposide and immune checkpoint inhibitors. Atezolizumab (Tecentriq®, Roche) and
durvalumab (Imfinzi®, AstraZeneca), two anti-Programmed death-ligand 1 (PD-L1)
antibodies, delivered positive phase III results, respectively through the Impower-133
and CASPIAN studies, and were granted European market authorisations.
Durvalumab is approved for use in combination with etoposide and either carboplatin or
cisplatin for the first-line treatment of patients with ES-SCLC. On March 10, 2020 French
health authorities allowed durvalumab utilization in this setting through a national
"early access program" (Autorisation Temporaire d'Utilisation "de cohorte" - ATUc), thus
preceding the European market authorization (August 28, 2020). Since 2020 October 1st,
durvalumab is used as a post ATU treatment. Since 2020, French AURA treatment guidelines
for SCLC have referenced durvalumab in combination with chemotherapy as a first-line
treatment option for patients with ES-SCLC.
Whereas the safety and efficacy of the durvalumab have been evaluated in a clinical
trial, data are required to further evaluate the use of durvalumab in real-life condition
and in less selected population than in clinical trials.
Detailed description:
Small cell lung cancer (SCLC), characterized by rapid proliferation, high growth fraction
and early development of metastases, is the most aggressive form of lung cancer. SCLC is
a relatively rare but really aggressive tumour accounting for 10-15% of all newly
diagnosed lung cancer. In 2021, an estimated 2.3 million people around the world are
diagnosed with lung cancer . In France, in 2018, with 46 363 new cases and 33 117 deaths,
lung cancer represented the second most common cancer and the first cause of death from
cancer. Among those, SCLC represented 10,8% of all new lung diagnosis, and about two
thirds presented at the extensive stage (ES-SCLC).
Between 2010 and 2018, the incidence rate increased of 0,3 % per year in men. In
contrast, from 1990 to 2018, the incidence increased more dramatically among women, with
an increase of 5% in average per year. The 5-year survival rate for all people with all
types of lung cancer is 21%. The 5-year survival rate is 17% and 24% for men and women,
respectively. For SCLC, due to the rapid proliferation and high growth fraction
associated to early development of metastases in the disease course (most commonly to the
brain, liver, or bone), the 5-year survival rate is low at 10%. Therefore, SCLC is the
most lethal lung cancer subtype. Most cases of SCLC develop in patients aged 60-80 years
and the estimated overall death rate is 25,000-30,000 per year in United States. More
than 90% of patients with SCLC are elderly and have heavy smoking histories.
SCLC is defined histologically as "a malignant epithelial tumour consisting of small
cells with scant cytoplasm, ill-defined cell borders, finely granular nuclear chromatin,
and absent or inconspicuous nucleoli", assessed by imaging techniques such as
computerized tomography (CT), positron emission tomography (PET) and magnetic resonance
imaging (MRI).
The Veterans' Administration Lung Study Group (VALG) staging system is usually used in
the clinic routine to stage SCLC. Two categories represent SCLC, limited stage (LS) and
extensive stage (ES). Limited-stage small-cell lung cancer (LS-SCLC) is defined as tumour
confined to one hemithorax, with or without regional lymph-node involvement, which can be
safely encompassed in a tolerable radiation field, corresponding at stage I to III of TNM
system. ES-SCLC is defined as disease that cannot be safely encompassed in a tolerable
radiation field, corresponding to stage IV of TNM system.
The management of SCLC is complicated by aggressiveness and substantial comorbidities,
and impaired performance status. According to ESMO guidelines (2021), as well as in the
French guidelines from Auvergne Rhone Alpes region, the standard management design of
SCLC is described and outlined in Figure 1.
Since last three decades, standard treatment in ES-SCLC is based on combination
chemotherapy with a platinum agent and etoposide in first-line with or without concurrent
radiation therapy. Then, the second-line of treatment is topotecan, with few results in
term of response rates and survival rate.
However, the emergence of immune checkpoint inhibitors targeting the programmed cell
death receptor-1 (PD-1)/PD-ligand 1 (PD-L1) pathway, having an important role in immune
regulation became an alternative method in the management and care of disease. Indeed,
recent studies have shown an overall survival (OS) benefit for patients with ES-SCLC
treated in first line with a combination of platinum-etoposide and immune checkpoint
inhibitors. Atezolizumab (Tecentriq®, Roche) and durvalumab (Imfinzi®, AstraZeneca), two
anti-Programmed death-ligand 1 (PD-L1) antibodies, delivered positive phase III results,
respectively through the Impower-133 and CASPIAN studies, and were granted European
market authorisations.
Durvalumab (Imfinzi®, AstraZeneca), a fully human monoclonal antibody against programmed
cell death-ligand 1 (PD-L1), is approved for use in combination with etoposide and either
carboplatin or cisplatin for the first-line treatment of patients with ES-SCLC. On March
10, 2020 French health authorities allowed durvalumab utilization in this setting through
a national "early access program" (Autorisation Temporaire d'Utilisation "de cohorte" -
ATUc), thus preceding the European market authorization (August 28, 2020). Since 2020
October 1st, durvalumab is used as a post ATU treatment.
Since 2020, French AURA treatment guidelines for SCLC have referenced durvalumab in
combination with chemotherapy as one of the first-line treatment options for patients
with ES-SCLC based on evidence from the CASPIAN phase III international randomized
clinical trial, which demonstrated that adding durvalumab to chemotherapy significantly
improved the median overall survival (mOS; hazard ratio: 0.73, 95% confidence interval
(CI): 0.59-0.91) over chemotherapy alone.
Results from this CASPIAN study was recently updated with an assessment of 3-year overall
survival. As of 2021 March, with a median follow-up 39.4 months, durvalumab plus
chemotherapy continued to demonstrate a significant improvement OS versus chemotherapy
alone (P = 0.0003). Authors concluded three times more patients were estimated to be
alive at 3 years when treated with durvalumab plus chemotherapy versus chemotherapy, with
the majority still receiving durvalumab at data cut-off, further establishing durvalumab
plus chemotherapy as first-line standard of care for ES-SCLC.
To date, durvalumab has thus been available to first-line ES-SCLC patients and clinicians
have the choice between atezolizumab + carboplatin-etoposide, durvalumab + carbo- or
cisplatin-etoposide, and carbo- or cisplatin-etoposide alone.
Whereas the safety and efficacy of the durvalumab have been evaluated in clinical trial,
data are required to further evaluate the use of durvalumab in real-life condition and in
less selected population than in clinical trials, while it received EMA approval in 2020.
Some studies with durvalumab were performed in real-life, but only for non-SCLC.
This observational uncontrolled prospective cohort study is conducted to complement
evidence from the CASPIAN clinical trial and generate real-world evidence. There is
indeed a need to describe durvalumab use in the clinical practice for the treatment of
first-line ES-SCLC patients and broaden the CASPIAN results to real-life setting in
France.
Therefore, the aim of this study is to describe of platinum-etoposide and durvalumab
real-life utilization and effectiveness for first line ES-SCLC.
Criteria for eligibility:
Study pop:
- Total population: all patients enrolled
- Safety analysis set: the safety population will be defined as all patients who
receive at least one infusion of durvalumab.
- Full analysis set: the full analysis set will comprise all patients who receive at
least one infusion of durvalumab and meet eligibility criteria.
- Follow up analysis set: it will comprise all patients of the full analysis set who
have at least one follow up visit completed.
Sampling method:
Non-Probability Sample
Criteria:
Inclusion Criteria:
- Adult patients (at least 18 years of age at time of treatment decision),
- Patients with histologically or cytologically proven SCLC and extensive disease
according to the Veterans Administration Lung Study Group (VALSG) classification or
TNM staging (Brierley et al, 2017) before durvalumab + platinum-etoposide
treatment*,
- Patients newly treated in first line with durvalumab + platinum-etoposide**,
- Patients informed and not opposed to participating in the study.
Exclusion Criteria:
- Patients with contraindications to receiving durvalumab + platinum-etoposide,
- Patients participating in another interventional clinical trial for first line
ES-SCLC.
Gender:
All
Minimum age:
N/A
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Research Site
Address:
City:
Angers
Zip:
49933
Country:
France
Facility:
Name:
Research Site
Address:
City:
Argenteuil
Zip:
95107
Country:
France
Facility:
Name:
Research Site
Address:
City:
Avignon
Zip:
84000
Country:
France
Facility:
Name:
Research Site
Address:
City:
Avignon
Zip:
84918
Country:
France
Facility:
Name:
Research Site
Address:
City:
Bayonne
Zip:
64100
Country:
France
Facility:
Name:
Research Site
Address:
City:
Bordeaux Cedex
Zip:
33077
Country:
France
Facility:
Name:
Research Site
Address:
City:
Clermont-Ferrand
Zip:
63000
Country:
France
Facility:
Name:
Research Site
Address:
City:
Créteil
Zip:
94000
Country:
France
Facility:
Name:
Research Site
Address:
City:
Dijon
Zip:
21000
Country:
France
Facility:
Name:
Research Site
Address:
City:
Epagny Metz-Tessy
Zip:
74370
Country:
France
Facility:
Name:
Research Site
Address:
City:
Gleize
Zip:
69400
Country:
France
Facility:
Name:
Research Site
Address:
City:
La Roche sur Yon
Zip:
85925
Country:
France
Facility:
Name:
Research Site
Address:
City:
La Rochelle
Zip:
17000
Country:
France
Facility:
Name:
Research Site
Address:
City:
Le Chesnay-Rocquencourt
Zip:
78150
Country:
France
Facility:
Name:
Research Site
Address:
City:
Limoges
Zip:
87000
Country:
France
Facility:
Name:
Research Site
Address:
City:
Marseille
Zip:
13008
Country:
France
Facility:
Name:
Research Site
Address:
City:
Nancy
Zip:
54100
Country:
France
Facility:
Name:
Research Site
Address:
City:
Nimes
Zip:
30000
Country:
France
Facility:
Name:
Research Site
Address:
City:
Nîmes
Zip:
30900
Country:
France
Facility:
Name:
Research Site
Address:
City:
Osny
Zip:
95520
Country:
France
Facility:
Name:
Research Site
Address:
City:
Paris
Zip:
75005
Country:
France
Facility:
Name:
Research Site
Address:
City:
Pau
Zip:
64000
Country:
France
Facility:
Name:
Research Site
Address:
City:
Rennes
Country:
France
Facility:
Name:
Research Site
Address:
City:
Rouen
Zip:
76000
Country:
France
Facility:
Name:
Research Site
Address:
City:
Saint Gregoire
Zip:
35760
Country:
France
Facility:
Name:
Research Site
Address:
City:
Saint-Etienne
Zip:
42100
Country:
France
Facility:
Name:
Research Site
Address:
City:
Saint-Quentin
Zip:
2321
Country:
France
Facility:
Name:
Research Site
Address:
City:
Toulon
Zip:
83000
Country:
France
Facility:
Name:
Research Site
Address:
City:
Toulouse
Zip:
31076
Country:
France
Facility:
Name:
Research Site
Address:
City:
Toulouse
Zip:
31400
Country:
France
Facility:
Name:
Research Site
Address:
City:
Valenciennes
Zip:
59300
Country:
France
Facility:
Name:
Research Site
Address:
City:
Vannes
Zip:
56017
Country:
France
Facility:
Name:
Research Site
Address:
City:
Villeurbanne
Zip:
69100
Country:
France
Facility:
Name:
Research Site
Address:
City:
Évreux
Zip:
27015
Country:
France
Start date:
November 14, 2022
Completion date:
March 1, 2027
Lead sponsor:
Agency:
AstraZeneca
Agency class:
Industry
Collaborator:
Agency:
Kappa Santé
Agency class:
Industry
Source:
AstraZeneca
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05683977
http://oncologik.fr/referentiels/rrc/cancer-bronchique-a-petites-cellules
http://espacecancer.sante-ra.fr/Pages/referentiels.aspx
https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics.
