A multi-center phase II randomized study of CustOmized Neoadjuvant ThErapy vs Standard chemoTherapy in non-small cell lung cancer (NSCLC) patients with resectable stage IIIA (N2) disease (CONTEST trial)

INTERVENTION: Trade Name: TAXOTERE*INFUS FL 80MG/4ML Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: DOCETAXEL CAS Number: 114977‐28‐5 Current Sponsor code: NA Other descriptive name: NA Concentration unit: mg/m2 milligram(s)/square meter Concentration type: up to Concentration number: 75‐ Trade Name: NAVELBINE 10*IV 10MG 1ML Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: VINORELBINE CAS Number: 71486‐22‐1 Current Sponsor code: NA Other descriptive name: NA Concentration unit: mg/m2 milligram(s)/square meter Concentration type: up to Concentration number: 20‐ Trade Name: ALIMTA*1FL POLV 500MG Pharmaceutical Form: Powder for solution for infusion INN or Proposed INN: PEMETREXED CAS Number: 137281‐23‐3 Current Sponsor code: NA Other descriptive name: NA Concentration unit: mg/m2 milligram(s)/square meter Concentration type: up to Concentration number: 500‐ Trade Name: GEMCITABINA SUN*INF FL 200MG Pharmaceutical Form: Powder for solution for infusion INN or Proposed INN: GEMCITABINE CAS Number: 95058‐81‐4 Current Sponsor code: NA Other descriptive name: NA Concentration unit: mg/m2 milligram(s)/square meter Concentration type: up to Concentration number: 1200‐ Trade Name: IRESSA*30CPR RIV 250MG Pharmaceutical Form: Tablet INN or Proposed INN: GEFITINIB CAS Number: 184475‐35‐2 Current Sponsor code: NA Other descriptive name: NA Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 250‐ Trade Name: CISPLATINO EBEWE*EV 100ML100MG Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: CISPLATIN CAS Number: 15663‐27‐1 Current Sponsor code: NA Other descriptive name: NA Concentration unit: mg/m2 milligram(s)/square meter Concentration type: up to Concentration number: 75‐ Trade Name: CISPLATINO EBEWE*EV 100ML100MG Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: CISPLATIN CAS Number: 15663‐27‐1 Current Sponsor code: NA Other descript CONDITION: Non‐small cell lung cancer (NSCLC) ; MedDRA version: 14.1 Level: PT Classification code 10029520 Term: Non‐small cell lung cancer stage IIIA System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: To compare pathological complete response (PCR) of all subjects randomized, by treatment arm Primary end point(s): Pathologic Complete Response (PCR) per Independent Pathology Review Secondary Objective: To compare all randomized subjects by treatment arm for: • Response rate (RR) • Disease‐free survival (DFS) • Overall Survival and one, two and five year • Safety profile Timepoint(s) of evaluation of this end point: After surgical resection (24 months post study initiation) SECONDARY OUTCOME: Secondary end point(s): • Overall Survival (OS) • Disease‐Free Survival (DFS) • Overall Survival at 1, 2 and 5 years • Overall Response (OR) per RECIST v1.1 • Overall safety profile as characterized by type, frequency, severity of adverse events as graded by NCI Common Toxicity Criteria for Adverse Events version 4, timing and relationship to treatment on each arm, laboratory abnormalities observed. Timepoint(s) of evaluation of this end point: • Overall Survival (OS : at 1, 2 and 5 years ; • Disease‐Free Survival (DFS): at 1, 2 and 5 years ; • Overall Response (OR) per RECIST v1.1 : at the end of treatment (25 months post study initiation). INCLUSION CRITERIA: 1. Histologically confirmed NSCLC. For the purpose of randomization/stratification, the histologic subtype of NSCLC must be documented, preferably by World Health Organization/International Association for Study of Lung Cancer Histologic Classification of Lung Cancer criteria; however, the diagnosis of undifferentiated NSCLC or not otherwise specified (NOS) NSCLC are sufficient for enrollment and will be stratified as non‐squamous. 2. Specimen tumor tissue obtained from mediastinoscopy is required, and will be sent to the IST laboratory for molecular testing of tumor tissue. ECOG Performance status (PS) 0‐1. 3. Stage IIIA(N2) patients with technical operable disease limited to T1a,b, T2a,b N2 M0; T3 (>7 cm) N2 M0 are eligible. 4. Medically fit for resection by lobectomy or pneumonectomy. 5. Radiologically measurable disease by RECIST v1.1 criteria. 6. Prior surgery for NSCLC permitted if resected =5 years prior. 7. No prior chemotherapy, targeted‐therapy