Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
SAKK 16/08 Preoperative chemotherapy and radiotherapy concomitant to Cetuximab in non-small cell lung cancer (NSCLC) patients with IIIB disease. A multicenter phase II trial. Protocol synopsis Management of patients with locally advanced non-small cell lung cancer (NSCLC) remains a challenge. Both local relapses and distant metastases are frequent and lead to a poor prognosis with a 5-year overall survival estimated between 3% and 7% for inoperable disease. Staging has historically subdivided stage III disease into stage IIIA, considered potentially amenable to surgery and stage IIIB, treated by definitive radiotherapy (RT) or chemo-RT. Progress in anesthesia coupled with improved surgical techniques and surgical specialization allowed in recent years to redefine the surgical limits. Among the patients with locally advanced stage IIIB NSCLC, there is a group that is technically operable. Patients with N3 or T4 disease with involvement of the carina, the pulmonary artery, vertebral bodies or the vena cava may be technically resectable. Reports on carefully selected patients with stage IIIB disease have shown a similar survival to patients with stage IIIA disease, when treated with induction therapy followed by resection with 5-year survival rates up to 20-30%. The Swiss Group of Clinical Cancer Research (SAKK) has focused since several years on the improvement of the treatment of advanced non-small cell lung cancer. The present study should allow defining the best induction therapy for patients having an operable stage IIIB. Indeed, the combination of cisplatine and docetaxel used as an induction therapy in previous SAKK trials has shown its effectiveness. Within stages IIIB, the SAKK already demonstrated in the literature that this combined chemotherapy followed by radiotherapy as a preoperative phase gives promising results. In the present trial, cetuximab will be added at this preoperative scheme, in order to improve further this induction treatment. Cetuximab is a primary antibody already known to be effective in the treatment of several solid tumors and especially in the treatment of advanced non-small cell lung cancer. Moreover, its use in combination either chemotherapy or radiotherapy, seems to not induce further secondary effects. The translational part of this trial will explore some candidate molecular markers which could contribute to recognition of the patients who would benefit most from the addition of cetuximab to the induction treatment of chemo-RT. Markers helping to predict more generally a benefit from this trimodality approach will also be analyzed. OBJECTIVES The main objective of this trial is to evaluate efficacy and safety of sequential neoadjuvant chemo-radiotherapy with concomitant targeted therapy of cetuximab in patient with operable stage IIIB NSCLC. ENDPOINTS Primary endpoint: Progression free survival (PFS) at 1 year Secondary endpoints: Treatment-related death during chemo-immunotherapy, radio-immunotherapy and perioperatively Metabolic response evaluated by PET Response status after chemo-immunotherapy and after radio-immunotherapy Complete pathological response Overall survival PFS Adverse events Operability Resection Failure pattern Endpoints for additional research questions: FcR polymorphism Tumor immunohistochemical EGFR expression Tumor EGFR gene amplification (FISH) KRAS mutations Immunohistochemical ERCC1 expression Immunohistochemical GSTPI expression TRIAL DESIGN Prospective multicenter, phase II trial 12 weeks Cisplatin 50 mg/m2 on day 1 and 2 of 21 day cycles Docetaxel 85 mg/m2 day 1 of 21 day cycles 3 cycles Radiotherapy 44 Gy (PTV 1 = 30 Gy, PTV 2 = 14 Gy) 3 weeks Follow up 400 mg/m2 initial dose on day 1 250 mg/m2 weekly starting on day 8 Surgery Registration Cetuximab SELECTION OF PATIENTS Histologically proven NSCLC stage IIIB: T4N0-3M0 or T1-4N3M0 (according to Error! Reference source not found.). Excluded are IIIB stages with malignant pleural or pericardial effusion; invasion of the aorta, esophagus, myocardium and supraclavicular/scalene nodes N3; or stages IIIB defined only by satellite lesions in the same lobe. Performance status 0-1 Patient medically fit for all protocol therapy, including operability Age 18-75 Written informed consent No previous chemo- or radiotherapy TRIAL DURATION The inclusion of patients is planned to start in Q3 2009 and will stop after the inclusion of 69 patients, which is expected in Q3 2012. End of trial treatment (last patient, last treatment visit) is expected for Q1 2013. STATISTICAL CONSIDERATIONS The sample size is calculated for PFS at 1 year. The PFS rate of ≤ 50% is considered uninteresting and ≥ 65% promising. Fleming- A’Hern single-stage phase II procedure with a power of 80%, a significance level of 5% and a sample size of 69 evaluable patients is chosen.