AzTrials
AzTrials

Large Cell Neuroendocrine Carcinoma of the LungPhase 2FIRST-NECNCT06393816

FIRST-NEC (GFPC 01-2022) - Combination of Durvalumab With Etoposide and Platinum

A Phase 2 study testing Durvalumab with etoposide and Carboplatin/Cisplatin in people with Large Cell Neuroendocrine Carcinoma of the Lung, run by Centre Leon Berard at 31 sites in 2 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Durvalumab with etoposide and Carboplatin/Cisplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
31 sitesin 2 countries
Study dates
13 Jun 2024to Sep 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
  • 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.
Show all 26Show fewer
  • Measurable disease as per the RECIST 1.1;
  • Performance Status (PS) of the Eastern Cooperative Oncology Group (ECOG): 0 or 1 ;
  • Body weight > 30Kg;
  • Must have a life expectancy of at least 12 weeks;
  • 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.
  • 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).
  • 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;
  • 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.
  • Affiliation to a social security system;
  • 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.

Who cannot join

  • 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;
  • 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.
  • History of allogenic organ transplantation;
Show all 32Show fewer
  • 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
  • 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;
  • 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.
  • 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;
  • Carcinomatous meningitis;
  • Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms;
  • History of active primary immunodeficiency;
  • 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;
  • Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) or active tuberculosis infection;
  • 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)
  • 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.
  • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients;
  • Pregnant or breast-feeding woman

Trial locations and contacts

31 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

Julien GAUTIER contact

+33 4 26 55 68 29

julien.gautier@lyon.unicancer.fr

Luc ODIER, MD contact

lodier@hno.fr

31 sites in 2 countries

France30 sites, 22 recruiting

  • Centre Hospitalier Intercommunal Aix-Pertuis

    Aix-en-Provence, 13616

    Active, not recruiting

  • Chu Amiens Picardie Site Sud

    Amiens, 80054

    Gérarldine FRANCOIS, MD, +33 03.22.45.59.09, francois.geraldine@chu-amiens.fr

    Not yet recruiting

  • Chu Angers

    Angers, 49933

    Gregoire JUSTEAU, MD, 02.41.35.58.44, gregoire.justeau@chu-angers.fr

    Not yet recruiting

  • CENTRE HOSPITALIER d'AVIGNON

    Avignon, 84000

    Nicolas CLOAREC, MD, 04.32.75.93.30, cloarec.nicolas@ch-avignon.fr

    Not yet recruiting

  • CHU BREST Cavale Blanche

    Brest, 29200

    Renaud DESCOURT, MD, +33 02.98.22.34.28, renaud.descourt@chu-brest.fr

    Not yet recruiting

  • Centre Francois Baclesse

    Caen, 14076

    Hubert CURCIO, MD, +33 02.31.45.50.50, h.curcio@baclesse.unicancer.fr

    Not yet recruiting

  • Chu Gabriel Montpied

    Clermont-Ferrand, 63000

    Patrick MERLE, MD, 04.73.75.16.49, pmerle@chu-clermontferrand.fr

    Not yet recruiting

  • Centre Hospitalier Intercommunal de Creteil

    Créteil, 94000

    Jean Bernard AULIAC, MD, +33 01.57.02.21.01, jean-Bernard.auliac@chicreteil.fr

    Not yet recruiting

  • Chu Annecy Genevois

    Épagny, 74370

    Active, not recruiting

  • Chu Grenoble Alpes

    Grenoble, 38043

    Anne claire TOFFART, MD, +33 04.76.76.68.31, atoffart@chu-grenoble.fr

    Recruiting

  • Centre Oscar Lambret

    Lille, 59020

    Elisabeth GAYE, MD, +33 03.20.29.59.59, e-gaye@o-lambret.fr

    Not yet recruiting

  • Chu Dupuytren

    Limoges, 87042

    Alain VERGNENEGRE, MD, +33 05.55.05.66.29, alain.vergnenegre@unilim.fr

    Recruiting

  • Groupe Hospitalier Bretagne Sud

    Lorient, 56100

    régine LAMY, MD, +33 02.97.06.96.95, r.lamy@ghbs.bzh

    Not yet recruiting

  • Centre Leon Berard

    Lyon, 69008

    Active, not recruiting

  • APHM, hôpital nord

    Marseille, 13915

    Active, not recruiting

  • Grand Hopital de L'Est Francilien - Site de Meaux

    Meaux, 77100

    Active, not recruiting

  • GHRMSA, hôpital Emile Muller

    Mulhouse, 68100

    Active, not recruiting

  • CHU NICE

    Nice, 06001

    Jonathan BENZAQUEN, MD, 04.92.03.80.59, benzaquen.j@chu-nice.fr

    Not yet recruiting

  • Hopital Cochin

    Paris, 75014

    Marie WISLEZ, MD, +33 01.58.41.23.72, marie.wislez@aphp.fr

    Not yet recruiting

  • Hopital Tenon

    Paris, 75020

    Anthony CANELLAS, MD, +33 01.56.01.65.31, anthony.canellas@aphp.fr

    Not yet recruiting

  • Centre Francois Magendie

    Pessac, 33604

    Rémi VEILLON, MD, 05.57.65.63.38, remi.veillon@chu-bordeaux.fr

    Not yet recruiting

  • Hospices Civils de Lyon - Lyon Sud Hospital

    Pierre-Bénite, 69495

    Active, not recruiting

  • Centre Hospitalier de Cornouaille

    Quimper, 29107

    Florence VERGNE, +33 02.98.52.60.60, florence.vergne@ch-cornouaille.fr

    Not yet recruiting

  • CHU Rennes

    Rennes, 35000

    Charles RICORDEL, MD, +33 02.99.28.24.81, charles.ricordel@chu-rennes.fr

    Not yet recruiting

  • Institut de Cancerologie Strasbourg Europe

    Strasbourg, 67033

    Roland SCHOTT, MD, 03.68.76.71.39, r.schott@icans.eu

    Not yet recruiting

  • Hopitaux Universitaires de Strasbourg - Nouvel Hopital Civil

    Strasbourg, 67091

    Bertrand MENNECIER, MD, +33 03.69.55.09.05, bertrand.mennecier@chru-strasbourg.fr

    Not yet recruiting

  • Hopital Foch

    Suresnes, 92150

    Hélène DOUBRE, MD, 01.46.25.25.44, h.doubre@hopital-foch.com

    Not yet recruiting

  • Hia Saint Anne

    Toulon, 83800

    Olivier BYLICKI, 04.83.16.29.37, olivier.bylicki@intradef.gouf.fr

    Not yet recruiting

  • Chu Toulouse

    Toulouse, 31059

    Laurence BIGAY GAME, MD, 05.67.77.17.99, bigaygame.l@chu-toulouse.fr

    Not yet recruiting

  • Hopital Nord Ouest de Villefranche Sur Saone

    Villefranche-sur-Saône, 69655

    Active, not recruiting

Other trials in France

Reunion1 site, 1 recruiting

  • Chu Reunion

    Réunion, 97400

    Diane MOREAU, MD, +262.262.90.55.70, diane.moreau@chu-reunion.fr

    Not yet recruiting

Other trials in Reunion

About this study

Official title: A Multicenter Phase II Study Evaluating the Efficacy and Safety of the Combination of Durvalumab With Etoposide and Platinum as First Line Treatment in Patients With Large-cell Neuroendocrine Carcinomas (LCNECs) of the Lung

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

Read the 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.

Being tested
Durvalumab with etoposide and Carboplatin/Cisplatin
Keywords
Advanced, Large Cell Neuroendocrine Carcinoma, Lung Cancer
Medical subject headings
Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Durvalumab with etoposide and Carboplatin/CisplatinDrug

    Also called MEDI4736

    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
Study groups in NCT06393816
Study groupRoleWhat they receive
Experimental : Durvalumab with etoposide and Carboplatin/CisplatinExperimentalCombination of durvalumab with etoposide and platinum (either cisplatin or carboplatin) for the first-line treatment of patients with advanced LCNEC
Receives: Drug: Durvalumab with etoposide and Carboplatin/Cisplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 12 months

Secondary outcomes (5)

  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

    Measured: 12 weeks

  2. 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

    Measured: 12 weeks

  3. 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.

    Measured: 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 months

  4. 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

    Measured: from the date of first study treatment administration to the date of death from any cause, assessed up to 63 months

  5. Safety profile : description of treatment-emergent Adverse Events

    All adverse events (AE), all serious adverse events, all immune mediated AE and all Adverse Events of Special Interest will be described using the NCI-CTC version 5.0

    Measured: 27 months and 90 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 May 2024
  2. Study start13 Jun 2024
  3. Primary completionSep 2028 (estimated)
  4. Study completionSep 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Prospective, multicenter, open-label, phase II study with an external control arm (ESME AMLC database).
Masking
None (open label)
Enrolment
80 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06393816
Sponsor's protocol ID
ET23-132
Acronym
FIRST-NEC
Status last verified
Aug 2024
First submitted
17 Apr 2024
Last updated
2 Aug 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • De Montfort A, Perol D, Lupo-Mansuet A, Greillier L, Gautier J, Decroisette C, Chabaud S, Arpin D, Odier L. Development of an externally controlled trial from a single-arm study to assess first-line immunochemotherapy in advanced large cell neuroendocrine lung carcinomas: a study protocol from the FIRST-NEC GFPC 01-2022 trial. BMJ Open. 2026 Jul 29;16(7):e118897. doi: 10.1136/bmjopen-2026-118897.

    PubMed 42526918

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Durvalumab with etoposide and Carboplatin/Cisplatin in people with Large Cell Neuroendocrine Carcinoma of the Lung, run by Centre Leon Berard at 31 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 2 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in France, Reunion. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Julien GAUTIER (+33 4 26 55 68 29, julien.gautier@lyon.unicancer.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06393816, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in