A phase I/II randomised study of Tarceva® (erlotonib), used concurrently with thoracic radiation in patients with advanced non-small cell lung cancer

INTERVENTION: Phase I: All 18 patients will receive erlotonib 150 mg orally (po) once daily. This will be combined with radiotherapy consisting of an initial radiation dose of 30 Gy/10 factions (3 Gy, 5 days per week, 2 weeks) for the first 6 patients, with a view to dose escalation to 36 Gy/12 fractions with two further groups of 6 patients depending on observed dose limiting toxicity levels. Phase II: Radiotherapy will be administered to all patients at the optimal dose determined in Phase 1 ‐ either 30 Gy/10 fractions or 36 Gy/12 fractions. Half of patients will also receive erlotinib 150 mg po, once daily. Erlotinib and follow‐up will continue after the radiotherapy until disease progression or the development of grade 3 or 4 toxicity despite dose reduction. Follow‐up: Each subject is followed for 12 weeks including pre‐treatment and treatment visits, then monthly for 6 months if there is no progression and then annually until progression. CONDITION: Non‐small cell lung cancer (NSCLC) ; Cancer ; Malignant neoplasm of bronchus and lung PRIMARY OUTCOME: Phase I: Evaluation of early safety and efficacy of erlotinib by determining the maximum tolerated dose in combination with external beam radiotherapy; Phase II: Evaluation of disease control rate at 6 months SECONDARY OUTCOME: 1. Objective response rate, assessed by Response Evaluation Criteria in Solid Tumors (RECIST) at baseline, 6 weeks after radiotherapy treatment (Visit 9, Week 9) and 6 months.; 2. Duration of response ; 3. Time to progression ; 4. Time to distant failure ; 5. Overall survival ; 6. Safety INCLUSION CRITERIA: Patients (both males and females) with non‐small cell lung cancer (NSCLC) with: 1. Histologically or cytologically confirmed non‐small cell lung cancer 2. Unresectable stage III or metastatic disease suitable for fractionated palliative radiotherapy 3. One dimensionally measurable disease 4. No prior radiotherapy for this cancer 5. Forced expiratory volume in 1 second (FEV1) >1 6. Performance status less or equal to 2 7. Adequate haematologic function 8. Serum creatinine concentration >1.5 x upper limit or normal (ULN) and /or EDTA clearance >60 ml/min 9. Bilirubin level <1.5 x ULN 10. Age 18‐80 years 11. Females of child bearing potential must agree to comply with effective contraceptive measures