Trial Title:
FIRST-NEC (GFPC 01-2022) - Combination of Durvalumab With Etoposide and Platinum
NCT ID:
NCT06393816
Condition:
Large Cell Neuroendocrine Carcinoma of the Lung
Conditions: Official terms:
Carcinoma
Carcinoma, Neuroendocrine
Lung Neoplasms
Carboplatin
Etoposide
Durvalumab
Conditions: Keywords:
Advanced
Large Cell Neuroendocrine Carcinoma
Lung Cancer
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Prospective, multicenter, open-label, phase II study with an external control arm (ESME
AMLC database).
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Durvalumab with etoposide and Carboplatin/Cisplatin
Description:
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
Arm group label:
Experimental : Durvalumab with etoposide and Carboplatin/Cisplatin
Other name:
MEDI4736
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age ≥ 18 years at the time of study entry;
2. Locally documented histological diagnosis of Large-Cell NeuroEndocrine Carcinoma of
the lung (2021 WHO classification of Lung Tumors );
3. Patient must have sufficient material to achieve central histological confirmation
and exploratory analyses (1 representative FFPE block or at least 10 unstained
slides);
4. 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).
Nota Bene: patients with recurrence of local or locally advanced LCNEC are eligible
to the trial provided that recurrence occurs beyond 3 months after the last
chemotherapy administration.
For relapsing patients, tumor material collected at diagnosis can be used for the
FIRST-NEC trial if relapse occurs within two years of initial management and if
initial histologic tumor material is available.
5. Measurable disease as per the RECIST 1.1;
6. Performance Status (PS) of the Eastern Cooperative Oncology Group (ECOG): 0 or 1 ;
7. Body weight > 30Kg;
8. Must have a life expectancy of at least 12 weeks;
9. Adequate normal organ and marrow function as defined below:
- Haemoglobin ≥8.0 g/dL (with or without transfusion)
- Absolute neutrophil count (ANC) ≥1.5 × 109 /L
- Platelet count ≥100 × 109/L
- Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN)), or ≤3.0xULN
in case of liver metastases.
Note: this will not apply to patients with confirmed Gilbert's syndrome (persistent
or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of
hemolysis or hepatic pathology), who will be allowed only in consultation with their
physician.
- AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver
metastases are present, in which case it must be ≤5x ULN
- For patients undergoing a treatment by cisplatin: measured creatinine clearance
(CrCl) ≥60 mL/min or Calculated creatinine CrCl ≥60 mL/min by the CKD-EPI
equation or by 24-hour urine collection for determination of creatinine
clearance (CrCl).
Nota Bene: if creatinine clearance is <60 ml/min, patients must be treated with
carboplatin rather than cisplatin.
10. Evidence of post-menopausal status or negative urinary or serum pregnancy test for
female pre-menopausal patients. Women will be considered post-menopausal if they
have been amenorrheic for 12 months without an alternative medical cause. The
following age-specific requirements apply:
- Women <50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of exogenous hormonal
treatments and if they have luteinizing hormone and follicle-stimulating
hormone levels in the post-menopausal range for the institution or underwent
surgical sterilization (bilateral oophorectomy or hysterectomy).
- Women ≥50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of all exogenous hormonal
treatments, had radiation induced menopause with last menses >1 year ago, had
chemotherapy-induced menopause with last menses >1 year ago, or underwent
surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or
hysterectomy).
11. Patient (male or female) using a highly effective contraception as defined in during
the treatment period and at least up to 6 months after the last administration of
chemotherapy or 90 days after the last administration of durvalumab, whichever is
longer. Prior to dispensing study drugs, the investigator must confirm and document
the patient's (and his/her partner) use of highly effective contraceptive methods,
dates of negative pregnancy tests, and confirm the patient's understanding of the
teratogenic potential of study drugs;
12. Patient is willing and able to comply with the protocol for the duration of the
study including undergoing treatment and scheduled visits and examinations including
follow up.
13. Affiliation to a social security system;
14. Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in this
protocol. Written informed consent obtained from the patient prior to performing any
protocol-related procedures, including screening evaluations.
Exclusion Criteria:
1. 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);
2. Patient previously treated for a LCNEC in a metastatic setting;
3. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab;
4. 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;
5. Major surgical procedure (as defined by the Investigator) within 21 days prior to
the first dose of study drugs; Note: Local surgery or radiotherapy of isolated
lesions for palliative intent is acceptable.
6. History of allogenic organ transplantation;
7. Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with
the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis
syndrome, or Wegener syndrome [granulomatosis with polyangiitis], Graves' disease,
rheumatoid arthritis, hypophysitis, uveitis, etc).
The following are exceptions to this criterion:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
hormone replacement
- Any chronic skin condition that does not require systemic therapy
- Patients without active disease in the last 5 years may be included but only
after consultation with the study physician
- Patients with celiac disease controlled by diet alone
8. Uncontrolled intercurrent illness, including but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, unstable cardiac arrhythmia, interstitial lung disease, peripheral
neuropathy > grade II, serious chronic gastrointestinal conditions associated with
diarrhea, or psychiatric illness/social situations that would limit compliance with
study requirement, substantially increase risk of incurring AEs or compromise the
ability of the patient to give written informed consent;
9. History of another primary malignancy except for:
- Malignancy treated with curative intent and with no known active disease ≥5
years before the first dose of IP and of low potential risk for recurrence
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease
- Adequately treated carcinoma in situ without evidence of disease, or Gleason ≤6
prostate cancer.
10. Central Nervous System metastases, unless asymptomatic (including patients treated
with anticonvulsants) or previously treated (surgery or radiation therapy combined
with corticosteroids ≤10 mg per day) and stable at the time of randomization for at
least 15 days;
11. Carcinomatous meningitis;
12. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms;
13. History of active primary immunodeficiency;
14. Active hepatitis infection, positive hepatitis C virus (HCV) antibody, hepatitis B
virus (HBV) surface antigen (HBsAg) or HBV core antibody (anti-HBc), at screening.
Participants with a past or resolved HBV infection (defined as the presence of anti
HBc and absence of HBsAg) are eligible. Participants positive for HCV antibody are
eligible only if polymerase chain reaction is negative for HCV RNA;
15. Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV
1/2 antibodies) or active tuberculosis infection;
16. Current or prior use of immunosuppressive medication within 14 days before the first
dose of durvalumab. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
articular injection)
- Systemic corticosteroids at physiologic doses not to exceed "10 mg/day" of
prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication)
17. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
Note: Patients, if enrolled, should not receive live vaccine whilst receiving
durvalumab and up to 30 days after the last dose of durvalumab.
18. Known allergy or hypersensitivity to any of the study drugs or any of the study drug
excipients;
19. Pregnant or breast-feeding woman
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Centre Hospitalier Intercommunal Aix-Pertuis
Address:
City:
Aix-en-Provence
Zip:
13616
Country:
France
Status:
Active, not recruiting
Facility:
Name:
Chu Amiens Picardie Site Sud
Address:
City:
Amiens
Zip:
80054
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Gérarldine FRANCOIS, MD
Phone:
+33 03.22.45.59.09
Email:
francois.geraldine@chu-amiens.fr
Facility:
Name:
Chu Angers
Address:
City:
Angers
Zip:
49933
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Gregoire JUSTEAU, MD
Phone:
02.41.35.58.44
Email:
gregoire.justeau@chu-angers.fr
Facility:
Name:
CENTRE HOSPITALIER d'AVIGNON
Address:
City:
Avignon
Zip:
84000
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Nicolas CLOAREC, MD
Phone:
04.32.75.93.30
Email:
cloarec.nicolas@ch-avignon.fr
Facility:
Name:
CHU BREST Cavale Blanche
Address:
City:
Brest
Zip:
29200
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Renaud DESCOURT, MD
Phone:
+33 02.98.22.34.28
Email:
renaud.descourt@chu-brest.fr
Facility:
Name:
Centre Francois Baclesse
Address:
City:
Caen
Zip:
14076
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Hubert CURCIO, MD
Phone:
+33 02.31.45.50.50
Email:
h.curcio@baclesse.unicancer.fr
Facility:
Name:
Chu Gabriel Montpied
Address:
City:
Clermont-Ferrand
Zip:
63000
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Patrick MERLE, MD
Phone:
04.73.75.16.49
Email:
pmerle@chu-clermontferrand.fr
Facility:
Name:
Centre Hospitalier Intercommunal de Creteil
Address:
City:
Créteil
Zip:
94000
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Jean Bernard AULIAC, MD
Phone:
+33 01.57.02.21.01
Email:
jean-Bernard.auliac@chicreteil.fr
Facility:
Name:
Chu Grenoble Alpes
Address:
City:
Grenoble
Zip:
38043
Country:
France
Status:
Recruiting
Contact:
Last name:
Anne claire TOFFART, MD
Phone:
+33 04.76.76.68.31
Email:
atoffart@chu-grenoble.fr
Facility:
Name:
Centre Oscar Lambret
Address:
City:
Lille
Zip:
59020
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Elisabeth GAYE, MD
Phone:
+33 03.20.29.59.59
Email:
e-gaye@o-lambret.fr
Facility:
Name:
Chu Dupuytren
Address:
City:
Limoges
Zip:
87042
Country:
France
Status:
Recruiting
Contact:
Last name:
Alain VERGNENEGRE, MD
Phone:
+33 05.55.05.66.29
Email:
alain.vergnenegre@unilim.fr
Facility:
Name:
Groupe Hospitalier Bretagne Sud
Address:
City:
Lorient
Zip:
56100
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
régine LAMY, MD
Phone:
+33 02.97.06.96.95
Email:
r.lamy@ghbs.bzh
Facility:
Name:
Centre Leon Berard
Address:
City:
Lyon
Zip:
69008
Country:
France
Status:
Active, not recruiting
Facility:
Name:
APHM, hôpital nord
Address:
City:
Marseille
Zip:
13915
Country:
France
Status:
Active, not recruiting
Facility:
Name:
Grand Hopital de L'Est Francilien - Site de Meaux
Address:
City:
Meaux
Zip:
77100
Country:
France
Status:
Active, not recruiting
Facility:
Name:
GHRMSA, hôpital Emile Muller
Address:
City:
Mulhouse
Zip:
68100
Country:
France
Status:
Active, not recruiting
Facility:
Name:
CHU NICE
Address:
City:
Nice
Zip:
06001
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Jonathan BENZAQUEN, MD
Phone:
04.92.03.80.59
Email:
benzaquen.j@chu-nice.fr
Facility:
Name:
Hopital Cochin
Address:
City:
Paris
Zip:
75014
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Marie WISLEZ, MD
Phone:
+33 01.58.41.23.72
Email:
marie.wislez@aphp.fr
Facility:
Name:
Hopital Tenon
Address:
City:
Paris
Zip:
75020
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Anthony CANELLAS, MD
Phone:
+33 01.56.01.65.31
Email:
anthony.canellas@aphp.fr
Facility:
Name:
Centre Francois Magendie
Address:
City:
Pessac
Zip:
33604
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Rémi VEILLON, MD
Phone:
05.57.65.63.38
Email:
remi.veillon@chu-bordeaux.fr
Facility:
Name:
Hospices Civils de Lyon - Lyon Sud Hospital
Address:
City:
Pierre-Bénite
Zip:
69495
Country:
France
Status:
Active, not recruiting
Facility:
Name:
Centre Hospitalier de Cornouaille
Address:
City:
Quimper
Zip:
29107
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Florence VERGNE
Phone:
+33 02.98.52.60.60
Email:
florence.vergne@ch-cornouaille.fr
Facility:
Name:
CHU Rennes
Address:
City:
Rennes
Zip:
35000
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Charles RICORDEL, MD
Phone:
+33 02.99.28.24.81
Email:
charles.ricordel@chu-rennes.fr
Facility:
Name:
Institut de Cancerologie Strasbourg Europe
Address:
City:
Strasbourg
Zip:
67033
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Roland SCHOTT, MD
Phone:
03.68.76.71.39
Email:
r.schott@icans.eu
Facility:
Name:
Hopitaux Universitaires de Strasbourg - Nouvel Hopital Civil
Address:
City:
Strasbourg
Zip:
67091
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Bertrand MENNECIER, MD
Phone:
+33 03.69.55.09.05
Email:
bertrand.mennecier@chru-strasbourg.fr
Facility:
Name:
Hopital Foch
Address:
City:
Suresnes
Zip:
92150
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Hélène DOUBRE, MD
Phone:
01.46.25.25.44
Email:
h.doubre@hopital-foch.com
Facility:
Name:
Hia Saint Anne
Address:
City:
Toulon
Zip:
83800
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Olivier BYLICKI
Phone:
04.83.16.29.37
Email:
olivier.bylicki@intradef.gouf.fr
Facility:
Name:
Chu Toulouse
Address:
City:
Toulouse
Zip:
31059
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Laurence BIGAY GAME, MD
Phone:
05.67.77.17.99
Email:
bigaygame.l@chu-toulouse.fr
Facility:
Name:
Hopital Nord Ouest de Villefranche Sur Saone
Address:
City:
Villefranche-sur-Saône
Zip:
69655
Country:
France
Status:
Active, not recruiting
Facility:
Name:
Chu Annecy Genevois
Address:
City:
Épagny
Zip:
74370
Country:
France
Status:
Active, not recruiting
Facility:
Name:
Chu Reunion
Address:
City:
Réunion
Zip:
97400
Country:
Réunion
Status:
Not yet recruiting
Contact:
Last name:
Diane MOREAU, MD
Phone:
+262.262.90.55.70
Email:
diane.moreau@chu-reunion.fr
Start date:
June 13, 2024
Completion date:
September 2029
Lead sponsor:
Agency:
Centre Leon Berard
Agency class:
Other
Collaborator:
Agency:
Groupe Français de Pneumo-Cancérologie
Agency class:
Other
Source:
Centre Leon Berard
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06393816
