This is an open-label, randomised, two-arm, phase III, multi-centre clinical trial. 210 stage IB-IIIA, completely resected, non-small cell lung cancer patients will be enrolled in this trial to evaluate the disease free survival between experimental arm (Adjuvant Chemotherapy-Immunotherapy + maintenance adjuvant Immunotherapy) and control arm (Adjuvant Chemotherapy)
This is an open-label, randomised, two-arm, phase III, multicentre clinical trial.The total sample size is 210 and 105 per arm. The population to be included are stage IB-IIIA, completely resected, non-small cell lung cancer patients. Patients randomised to the experimental arm will receive Nivolumab 360mg + Paclitaxel 200mg/m2 + Carboplatin AUC5 for 4 cycles every 21 days (+/- 3 days) as adjuvant treatment followed by maintenance adjuvant treatment for 6 cycles with Nivolumab 480 mg Q4W (+/- 3 days). Patients randomized to the control arm will receive Paclitaxel 200mg/m2 + Carboplatin AUC5 for 4 cycles every 21 days (+/- 3 days) followed by 2 observation visits. The primary objective is to evaluate the disease-free survival (DFS): defined as the length of time from randomization to the earliest event defined as disease recurrence, any new lung cancer (even in the opposite lung), or death from any cause at any known point in time. Patient accrual is expected to be completed within 3.5 years, excluding a run-in-period of 3 months. Treatment and follow-up are expected to extend the study duration to a total of 8.5 years. Patients will be followed 5 years after adjuvant treatment or observation phase. The study will end once survival follow-up has concluded.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
210
Structure: The cis-diamino (cyclobutan-1, 1 dicarboxilate) plating. Stability: 24 hours at ambient temperature in 5% glucose, glucosaline or physiologic saline. It is recommended not to dilute with chlorinated solutions for this could affect the carboplatin. Route of administration: Intravenous infusion. Guidelines of Carboplatin administration: According to the standard of each center.
Structure: A diterpene whose composition is: 5b, 20-epoxy-1, 2a, 4,7b, 10b, 13a-hexa-hidroxytax-11-en 9 one 4,10-diacetate 2-benzoate 13-ester with (2R,3S)- N-benzoyl-3-phenylisoserine. Stability: Concentrations of 0.3-1.2 mg/ml in 5% dextrose or normal saline have demonstrated chemical and physical stability for more that 27 hours at ambient temperature (25ºC approximately). The intact vial must be stored between 15º and 25ºC. Guidelines on Paclitaxel administration: Paclitaxel must be administered by infusion over 3 hours in dextrose (D5W) or normal saline (NS). The concentration must not exceed 1.2 mg/ml.
The disease-free survival
The length of time from randomization to the earliest event defined as disease recurrence, any new lung cancer (even in the opposite lung), or death from any cause at any known point in time.
Time frame: From the date of randomization to the date of last follow up, assessed up to 60 months
Overall survival
Defined as the time between the date of randomization and the date of death
Time frame: From the date of randomization until the date of last follow up, assessed up to 60 months
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
It will be measured by the incidence of AE, SAE, immune-related AEs, deaths, and laboratory abnormalities. Adverse events will be graded according to CTCAE v5.0
Time frame: From the subject's written consent to participate in the study through 100 days after the final administration of the drug
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Structure: Nivolumab is a soluble protein consisting of 4 polypeptide chains. Route of administration: Intravenous infusion. Product Description: Nivolumab (BMS-936558-01) Injection drug product is a sterile, non-pyrogenic, single-use, isotonic aqueous solution formulated in 10 mg/ml. Storage Conditions: It must be stored at 2 to 8 degrees Cº and protected from light and freezing. Guidelines: The administration of nivolumab infusion must be completed within 24 hours of preparation.The dose of Nivolumab for the adjuvant treatment is 360 mg administered as an intravenous infusion over 30 minutes every 3 weeks (+/-3 days) for 4 cycles. For the maintenance adjuvant treatment the dose is nivolumab 480 mg Q4W (+/-3 days) over 30 minutes for 6 months (6 cycles). Subjects should be carefully monitored during nivolumab administration to follow infusion reactions. Doses of nivolumab may be interrupted, delayed, or discontinued depending on how well the subject tolerates the treatment.
Hospital General Universitario de Alicante
Alicante, Alicante, Spain
ICO Badalona, Hospital Germans Trias i Pujol
Badalona, Barcelona, Spain
Hospital Universitari Quiron Dexeus
Barcelona, Barcelona, Spain
Hospital Universitari Vall d' Hebron
Barcelona, Barcelona, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, Barcelona, Spain
Hospital Parc Taulí
Barcelona, Barcelona, Spain
ICO Hospitalet
L'Hospitalet de Llobregat, Barcelona, Spain
Hospital de Basurto
Bilbao, Bilbao, Spain
Hospital San Pedro De Alcántara
Cáceres, Cáceres, Spain
Hospital Universitario Virgen de la Arrixaca
El Palmar, El Palmar, Spain
...and 20 more locations