Home › Trials › NCT06393816

Combining Durvalumab with Etoposide and Platinum for Lung Cancer Treatment

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

Phase 2 Interventional Centre Leon Berard · NCT06393816

This study is testing if combining a new immune therapy with chemotherapy can help people with advanced lung cancer feel better and live longer.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment80 (estimated)
Ages18 Years and up
SexAll
SponsorCentre Leon Berard Academic / other
Drugs / interventionsdurvalumab, chemotherapy, radiation, prednisone, nivolumab, ipilimumab
Locations31 sites (Aix-en-Provence and 30 other locations)
Trial IDNCT06393816 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of durvalumab, an immune checkpoint inhibitor, in combination with etoposide and platinum-based chemotherapy for patients with advanced large cell neuroendocrine carcinoma (LCNEC) of the lung. The study focuses on patients who have a confirmed diagnosis of LCNEC and are receiving first-line treatment. The primary goal is to assess the progression-free rate at 12 months, building on previous findings that suggest potential benefits of immunotherapy in this patient population. The trial will also involve centralized expert-pathologist review to confirm histological diagnosis.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with a confirmed diagnosis of locally advanced or metastatic large cell neuroendocrine carcinoma of the lung.

Not a fit: Patients with early-stage LCNEC or those who have previously received treatment for this condition may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment combination could significantly improve progression-free survival and overall outcomes for patients with advanced LCNEC.

How similar studies have performed: Previous studies have shown promising results with similar approaches, particularly the efficacy of immune checkpoint inhibitors in treating LCNEC.

Eligibility criteria

Show full inclusion / exclusion 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

Where this trial is running

Aix-en-Provence and 30 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Large Cell Neuroendocrine Carcinoma of the LungAdvancedLarge Cell Neuroendocrine CarcinomaLung Cancer
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.