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

NCT06393816 | Recruiting Phase 2 DMC

• 1 other identifier: ET23-132
• Study Type: interventional
• Target: 80
• Locations: 2 countries
• Sites: 31

Brief 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

Conditions

Large Cell Neuroendocrine Carcinoma of the Lung

Keywords

Advanced; Large Cell Neuroendocrine Carcinoma; Lung Cancer

Outcome Measures

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

  12 months

Secondary Outcomes (5)

• 12-week Objective Response Rate (ORR)

  12 weeks

• 12-week Disease Control Rate

  12 weeks

• Progression-Free Survival (PFS)

  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

• Overall Survival

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

• Safety profile : description of treatment-emergent Adverse Events

  27 months and 90 days

Other Outcomes (6)

• Treatment effectiveness of the experimental combination compared to an external control arm

  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 months

• Histopathological diagnosis concordance rate

  Through central histopathological completion, an average of 6 weeks

• 12-week Objective Response Rate as a predictive and prognostic factors

  12 weeks

Study Arms (1)

Experimental : Durvalumab with etoposide and Carboplatin/Cisplatin

EXPERIMENTAL

Combination of durvalumab with etoposide and platinum (either cisplatin or carboplatin) for the first-line treatment of patients with advanced LCNEC

Drug: Durvalumab with etoposide and Carboplatin/Cisplatin

Interventions

Durvalumab with etoposide and Carboplatin/Cisplatin DRUG

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

Also known as: MEDI4736

Experimental : Durvalumab with etoposide and Carboplatin/Cisplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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;
• 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:

Sponsors & Collaborators

• Centre Leon Berard: lead
• Groupe Francais De Pneumo-Cancerologie: collaborator

Study Sites (31)

Centre Hospitalier Intercommunal Aix-Pertuis

Aix-en-Provence, 13616, France

ACTIVE NOT RECRUITING

Chu Amiens Picardie Site Sud

Amiens, 80054, France

NOT YET RECRUITING

Chu Angers

Angers, 49933, France

NOT YET RECRUITING

CENTRE HOSPITALIER d'AVIGNON

Avignon, 84000, France

NOT YET RECRUITING

CHU BREST Cavale Blanche

Brest, 29200, France

NOT YET RECRUITING

Centre Francois Baclesse

Caen, 14076, France

NOT YET RECRUITING

Chu Gabriel Montpied

Clermont-Ferrand, 63000, France

NOT YET RECRUITING

Centre Hospitalier Intercommunal de Creteil

Créteil, 94000, France

NOT YET RECRUITING

Chu Annecy Genevois

Épagny, 74370, France

ACTIVE NOT RECRUITING

Chu Grenoble Alpes

Grenoble, 38043, France

RECRUITING

Centre Oscar Lambret

Lille, 59020, France

NOT YET RECRUITING

Chu Dupuytren

Limoges, 87042, France

RECRUITING

Groupe Hospitalier Bretagne Sud

Lorient, 56100, France

NOT YET RECRUITING

Centre Leon Berard

Lyon, 69008, France

ACTIVE NOT RECRUITING

APHM, hôpital nord

Marseille, 13915, France

ACTIVE NOT RECRUITING

Grand Hopital de L'Est Francilien - Site de Meaux

Meaux, 77100, France

ACTIVE NOT RECRUITING

GHRMSA, hôpital Emile Muller

Mulhouse, 68100, France

ACTIVE NOT RECRUITING

CHU NICE

Nice, 06001, France

NOT YET RECRUITING

Hopital Cochin

Paris, 75014, France

NOT YET RECRUITING

Hopital Tenon

Paris, 75020, France

NOT YET RECRUITING

Centre Francois Magendie

Pessac, 33604, France

NOT YET RECRUITING

Hospices Civils de Lyon - Lyon Sud Hospital

Pierre-Bénite, 69495, France

ACTIVE NOT RECRUITING

Centre Hospitalier de Cornouaille

Quimper, 29107, France

NOT YET RECRUITING

CHU Rennes

Rennes, 35000, France

NOT YET RECRUITING

Institut de Cancerologie Strasbourg Europe

Strasbourg, 67033, France

NOT YET RECRUITING

Hopitaux Universitaires de Strasbourg - Nouvel Hopital Civil

Strasbourg, 67091, France

NOT YET RECRUITING

Hopital Foch

Suresnes, 92150, France

NOT YET RECRUITING

Hia Saint Anne

Toulon, 83800, France

NOT YET RECRUITING

Chu Toulouse

Toulouse, 31059, France

NOT YET RECRUITING

Hopital Nord Ouest de Villefranche Sur Saone

Villefranche-sur-Saône, 69655, France

ACTIVE NOT RECRUITING

Chu Reunion

Réunion, 97400, Reunion

NOT YET RECRUITING

MeSH Terms

Conditions

Lung Neoplasms

Interventions

durvalumab; Etoposide; Carboplatin; Cisplatin

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Coordination Complexes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Luc ODIER, MD

  Hôpital Nord-Ouest, Villefranche sur Saône

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Julien GAUTIER

CONTACT

+33 4 26 55 68 29; julien.gautier@lyon.unicancer.fr

Luc ODIER, MD

CONTACT

lodier@hno.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, multicenter, open-label, phase II study with an external control arm (ESME AMLC database).

Study Record Dates

• First Submitted: April 17, 2024
• First Posted: May 1, 2024
• Study Start: June 13, 2024
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2029
• Last Updated: August 2, 2024

Record last verified: 2024-08

Locations

RE (1); FR (30)