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FIRST-NEC (GFPC 01-2022) - Combination of Durvalumab With Etoposide and Platinum
Bu çalışma, akciğerin büyük hücreli nöroendokrin karsinomu (large-cell neuroendocrine carcinoma) olan hastalarda ilk basamak tedavi olarak Durvalumab'ın etoposid ve platin (karboplatin/sisplatin) ile kombinasyonunu incelemektedir. Çalışmaya, histolojik olarak doğrulanmış, lokal ileri veya metastatik hastalığı olan 18 yaş ve üzeri hastalar alınmaktadır. Çalışma Faz 2 aşamasında yürütülmekte ve halen katılımcı almaktadır.
Yukarıdaki özet, resmî kaydın sade dile aktarılmış halidir. Orijinal İngilizce başlık referans için gösterilir.
Kriterler ClinicalTrials.gov kaydından orijinal İngilizce haliyle alınmıştır. Uygunluk kararını yalnızca deneyi yürüten ekip verebilir.
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