ISoToxic Accelerated RadioTherapy in Locally Advanced Non-small Cell Lung Cancer: The Phase I/II I-START Trial

Main inclusion criteria: 1. Histologically or cytologically confirmed stage II - IIIb NSCLC (see appendix II) 2. Inoperable disease (as assessed by a lung cancer MDT with thoracic surgical input) or operable but the patient refuses surgery 3. Disease which can be encompassed within a radical radiotherapy treatment plan in keeping with standard practice at the participating centre 4. WHO Performance Status 0 or 1 (Appendix III) 5. Adequate respiratory function: FEV1 ≥ 1.0 litre, DLco (transfer factor) ≥ 40% of predicted and Kco (DLco/VA) \> 40% predicted on baseline lung function tests 6. Blood Haemoglobin ≥ 10g/dL 7. No prior thoracic radiotherapy 8. Age ≥ 16 years 9. Considered fit to receive trial treatment 10. Estimated life expectancy of more than 3 months 11. Written informed consent obtained 12. Patient consents for electronic CT scan and planning data to be used for future research Main exclusion criteria: 1. Medically unstable (e.g. unstable diabetes, uncontrolled hypertension, infection, hypercalcaemia or very symptomatic ischaemic heart disease) 2. Previous or current malignant disease likely to interfere with protocol treatment 3. Pancoast tumours 4. Connective tissue disorders (e.g. Scleroderma, Systemic Lupus Erythematosus) 5. Interstitial lung disease 6. Women who are pregnant or lactating 7. Women of childbearing potential who are not using adequate contraceptive precautions Primary outcome measure: Phase I: • Establish the maximum tolerated dose (MTD) to the oesophagus to use as the recommended Phase II dose. Phase II: • Toxicity rate (grade 3 and 4) at three months. Secondary outcome measures Phase I: • Chronic oesophagitis or stricture occurring/persisting two months or more after completion of radiotherapy Phase II: * Local control at three months (to include complete response, partial response and stable disease) * Feasibility * Time to Local Progression; measured in days from the day of trial entry to the date of first clinical evidence of progressive disease at the primary site * Time to distant metastases measured in days * Overall Survival; measured in days, from the day of trial entry to the day of death (from any cause) * Toxicity; pulmonary, oesophageal, spinal cord and cardiac grade 3 or 4 toxicity occurring up to three months after radiotherapy * Radiotherapy Quality Assurance. A detailed QA program will be in place to ensure adherence to the protocol. Major and minor deviations will be documented