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

Main inclusion criteria:

• Histologically or cytologically confirmed stage II - IIIb NSCLC (see appendix II)
• Inoperable disease (as assessed by a lung cancer MDT with thoracic surgical input) or operable but the patient refuses surgery
• Disease which can be encompassed within a radical radiotherapy treatment plan in keeping with standard practice at the participating centre
• WHO Performance Status 0 or 1 (Appendix III)
• Adequate respiratory function: FEV1 ≥ 1.0 litre, DLco (transfer factor) ≥ 40% of predicted and Kco (DLco/VA) > 40% predicted on baseline lung function tests
• Blood Haemoglobin ≥ 10g/dL
• No prior thoracic radiotherapy
• Age ≥ 16 years
• Considered fit to receive trial treatment
• Estimated life expectancy of more than 3 months
• Written informed consent obtained
• Patient consents for electronic CT scan and planning data to be used for future research

Main exclusion criteria:

• Medically unstable (e.g. unstable diabetes, uncontrolled hypertension, infection, hypercalcaemia or very symptomatic ischaemic heart disease)
• Previous or current malignant disease likely to interfere with protocol treatment
• Pancoast tumours
• Connective tissue disorders (e.g. Scleroderma, Systemic Lupus Erythematosus)
• Interstitial lung disease
• Women who are pregnant or lactating
• 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

Inclusion criteria

• Histologically or cytologically confirmed stage II - IIIb NSCLC (see appendix II)
• Inoperable disease (as assessed by a lung cancer MDT with thoracic surgical input) or operable but the patient refuses surgery
• Disease which can be encompassed within a radical radiotherapy treatment plan in keeping with standard practice at the participating centre
• WHO Performance Status 0 or 1 (Appendix III)
• Adequate respiratory function: FEV1 ≥ 1.0 litre, DLco (transfer factor) ≥ 40% of predicted and Kco (DLco/VA) > 40% predicted on baseline lung function tests
• Blood Haemoglobin ≥ 10g/dL
• No prior thoracic radiotherapy
• Age ≥ 16 years
• Considered fit to receive trial treatment
• Estimated life expectancy of more than 3 months
• Written informed consent obtained
• Patient consents for electronic CT scan and planning data to be used for future research
• Patient is available for follow up

Exclusion criteria

• Medically unstable (e.g. unstable diabetes, uncontrolled hypertension, infection, hypercalcaemia or very symptomatic ischaemic heart disease)
• Previous or current malignant disease likely to interfere with protocol treatment
• Pancoast tumours
• Connective tissue disorders (e.g. Scleroderma, Systemic Lupus Erythematosus)
• Interstitial lung disease
• Women who are pregnant or lactating
• Women of childbearing potential who are not using adequate contraceptive precautions