Informations générales (source: ClinicalTrials.gov)
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 (FIRST-NEC)
Interventional
Phase 2
Centre Leon Berard (Voir sur ClinicalTrials)
juin 2024
septembre 2029
03 août 2024
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
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| HOPITAL FOCH | HELENE DOUBRE | 05/05/2025 07:12:15 | Contacter | ||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| AP-HP - Hôpital Cochin | Marie WISLEZ, MD | Contact (sur clinicalTrials) | |||
| AP-HP - Hôpital Tenon | Anthony CANELLAS, MD | Contact (sur clinicalTrials) | |||
| CHI DE CRETEIL | Jean Bernard AULIAC, MD | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| APHM, hôpital nord - 13915 - Marseille - France | Contact (sur clinicalTrials) | ||||
| Centre Francois Baclesse - 14076 - Caen - France | Hubert CURCIO, MD | Contact (sur clinicalTrials) | |||
| Centre Francois Magendie - 33604 - Pessac - France | Rémi VEILLON, MD | Contact (sur clinicalTrials) | |||
| CENTRE HOSPITALIER d'AVIGNON - 84000 - Avignon - France | Nicolas CLOAREC, MD | Contact (sur clinicalTrials) | |||
| Centre Hospitalier de Cornouaille - 29107 - Quimper - France | Florence VERGNE | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Intercommunal Aix-Pertuis - 13616 - Aix-en-Provence - France | Contact (sur clinicalTrials) | ||||
| Centre Leon Berard - 69008 - Lyon - France | Contact (sur clinicalTrials) | ||||
| Centre Oscar Lambret - 59020 - Lille - France | Elisabeth GAYE, MD | Contact (sur clinicalTrials) | |||
| Chu Amiens Picardie Site Sud - 80054 - Amiens - France | Gérarldine FRANCOIS, MD | Contact (sur clinicalTrials) | |||
| Chu Angers - 49933 - Angers - France | Gregoire JUSTEAU, MD | Contact (sur clinicalTrials) | |||
| Chu Annecy Genevois - 74370 - Épagny - France | Contact (sur clinicalTrials) | ||||
| CHU BREST Cavale Blanche - 29200 - Brest - France | Renaud DESCOURT, MD | Contact (sur clinicalTrials) | |||
| Chu Dupuytren - 87042 - Limoges - France | Alain VERGNENEGRE, MD | Contact (sur clinicalTrials) | |||
| Chu Gabriel Montpied - 63000 - Clermont-Ferrand - France | Patrick MERLE, MD | Contact (sur clinicalTrials) | |||
| Chu Grenoble Alpes - 38043 - Grenoble - France | Anne claire TOFFART, MD | Contact (sur clinicalTrials) | |||
| CHU NICE - 06001 - Nice - France | Jonathan BENZAQUEN, MD | Contact (sur clinicalTrials) | |||
| CHU Rennes - 35000 - Rennes - France | Charles RICORDEL, MD | Contact (sur clinicalTrials) | |||
| Chu Toulouse - 31059 - Toulouse - France | Laurence BIGAY GAME, MD | Contact (sur clinicalTrials) | |||
| GHRMSA, hôpital Emile Muller - 68100 - Mulhouse - France | Contact (sur clinicalTrials) | ||||
| Grand Hopital de L'Est Francilien - Site de Meaux - 77100 - Meaux - France | Contact (sur clinicalTrials) | ||||
| Groupe Hospitalier Bretagne Sud - 56100 - Lorient - France | régine LAMY, MD | Contact (sur clinicalTrials) | |||
| Hia Saint Anne - 83800 - Toulon - France | Olivier BYLICKI | Contact (sur clinicalTrials) | |||
| Hopital Nord Ouest de Villefranche Sur Saone - 69655 - Villefranche-sur-Saône - France | Contact (sur clinicalTrials) | ||||
| Hopitaux Universitaires de Strasbourg - Nouvel Hopital Civil - 67091 - Strasbourg - France | Bertrand MENNECIER, MD | Contact (sur clinicalTrials) | |||
| Hospices Civils de Lyon - Lyon Sud Hospital - 69495 - Pierre-Bénite - France | Contact (sur clinicalTrials) | ||||
| Institut de Cancerologie Strasbourg Europe - 67033 - Strasbourg - France | Roland SCHOTT, MD | Contact (sur clinicalTrials) | |||
Critères
Tous
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.
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.
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