This study is designed as a single arm, un-controlled, open-label, multi-center hypothesis generating two-stage phase II trial. It is based on the assumption that the proposed treatment scheme doubles the rate of pathologic complete remission in Mutated epidermal growth factor receptor (EGFRmt) + NSCLC patients compared to historical control data from standard treatments. Patients with NSCLC and activating EGFR mutation in stages II, IIIA and IIIB eligible for induction therapy with docetaxel and cisplatin and gefitinib Patients will be treated for 12 days with gefitinib 250 mg/day p.o. (d -12 to -1) and induced with chemotherapy docetaxel 75 mg/m2 and cisplatin 50 mg/m2 d1+2 and intercalated gefitinib 250 mg/day d4-20 (cycle 1 and 2) and d4-17 (for cycle3). Surgery is planned in the 4th week after d1 of the last cycle.
Name: Gefitinib
Description: Patients will be treated for 12 days with gefitinib 250 mg/day p.o. (d -12 to -1) and induced with chemotherapy docetaxel 75 mg/m2 and cisplatin 50 mg/m2 d1+2 and intercalated gefitinib 250 mg/day d4-20 (cycle 1 and 2) and d4-17 (for cycle3). Surgery is planned in the 4th week after d1 of the last cycle.Type: DrugTreatment phase
Name: docetaxel
Description: chemotherapy docetaxel 75 mg/m2 and cisplatin 50 mg/m2 d1+2 and intercalated gefitinib 250 mg/day d4-20 (cycle 1 and 2) and d4-17 (for cycle3).Type: DrugTreatment phase
Name: cisplatin
Description: chemotherapy docetaxel 75 mg/m2 and cisplatin 50 mg/m2 d1+2 and intercalated gefitinib 250 mg/day d4-20 (cycle 1 and 2) and d4-17 (for cycle3).Type: DrugTreatment phase
Name: Surgery
Description: Surgery should be performed in the 4th or at the latest 5th week after d1 of the last cycle of chemotherapy (d64 to 78).Type: ProcedureTreatment phase
Description: The primary objective of the study is to assess the pathologic complete remission rate after induction therapy with gefitinib d -12 to d-1 followed by docetaxel 75 mg/m2 and cisplatin 50 mg/m2 d1+2 q21 and intercalated gefitinib 250 mg d4 to d20 (cycle 1 and 2) and d4-17 (for cycle3), in order to demonstrate feasibility and efficacy of this treatment scheme. It is expected to achieve a pCR ≥30% regression grade IIB and III (Junker criteria) compared to historical controls in the mediastinal lymph nodes.
Measure: pathologic complete remission rate (pCR rate) Time: 12 weeks (after 3 cycles and surgery) after enrollmentDescription: AEs/SAEs from 21 patients during induction CTx with docetaxel and cisplatin in combination with intercalated gefitinib
Measure: Adverse Events (AEs) / Serious adverse events (SAEs) Time: 30 monthsDescription: R0 resection rate as assessed according to the German S3 guidelines
Measure: Surgical R0 resection rate Time: 30 monthDescription: Progression-free survival (PFS) will be defined as the time from enrollment to the time of disease progression or relapse or death, or to the date of last assessment without any such event (censored observation).
Measure: progression free survival (PFS) Time: 30 monthDescription: The duration of overall survival (OS) will be determined by measuring the time interval from enrollment to the date of death or last observation (censored).
Measure: Overall survival (OS) Time: 30 monthDescription: After the end of treatment will be performed every 3 month (+/- 14 days) for minimum 12 months in order to collect information on relapse and site of relapse
Measure: relapse pattern Time: 30 monthDescription: Explorative analysis of health related quality of life, QoL at various time points throughout the study, to assess the QoL during and after induction therapy with gefitinib, after three cycles of chemotherapy with intercalated gefitinib including pre- and post surgery
Measure: quality of life Time: 30 monthDescription: To collect and store tumor tissue as well as plasma and serum samples for exploratory analyses of potential predictive markers, monitoring of biomarkers during and after treatment
Measure: translational research Time: 30 monthDescription: analysis of EGFR ctDNA in patient plasma; screening for EGFR mutation status (activating and resistance mutations especially T790M), monitoring of EGFR mutation status by means of Circulating tumor DNA (ctDNA) detection in patient plasma
Measure: monitoring of epidermal growth factor receptor (EGFR) mutation status Time: 30 monthSingle Group Assignment
There is one SNP
analysis of EGFR ctDNA in patient plasma; screening for EGFR mutation status (activating and resistance mutations especially T790M), monitoring of EGFR mutation status by means of Circulating tumor DNA (ctDNA) detection in patient plasma. --- T790M ---
T790M); 3. Significant cardiovascular disease, such as uncontrolled hypertension, myocardial infarction within the last 6 months, unstable angina pectoris, CHF ≥ NYHA 2, serious arrhythmia, significant peripheral vascular disease; 4. Pre-existing neuropathic ≥ grade 2; 5. Patients with confirmed HIV infection. --- T790M ---