Photodynamic Therapy for the Prevention of Lung Cancer

Inclusion Criteria:

1. Patients with ≥1 histologically confirmed lung HGL (defined as severe dysplasia orcarcinoma in situ) PRE-REGISTRATION: High likelihood of presence of lung HGLs asevaluated by investigator (e.g. because patient part of existing surveillance cohortor referred to trial site) and inclusion/exclusion criteria below. PRE-RANDOMISATION:Following registration and AFB, only patients with ≥1 lung HGLs confirmedhistologically can be continue to randomisation provided they continue to meetinclusion/exclusion criteria below.

2. Absence of metastatic disease or other primary cancers as confirmed by CT thoraxwithin 28 days prior to registration only)

3. Male or female patients ≥18 years of age

4. No upper age limit but life expectancy must be at least 3 years

5. ECOG Performance Score 0-2

6. FEV1 ≥ 25% of predicted

7. DLCO/TLCO ≥ 20% of predicted (within 28 days prior to registration only)

8. Women of child-bearing potential (WOCBP), or men with female partners who are pregnantor WOCBP must be willing to practise highly effective methods of birth controlstarting as soon as possible from the time of informed consent and registration untilrandomisation (if randomised to the control arm), or until 3 months after the end oftheir last PDT treatment (if randomised to the intervention arm) . Male patients mustalso advise their female partners who are WOCBP regarding contraceptive requirementsas listed for female patients who are WOCBP.

9. Patients who are WOCBP must also have a negative pregnancy test at the following timepoints:

• within 14 days prior to registration

• within 21 days prior to randomisation

• and within 24 hours prior to 1st and 2nd PDT treatment, for each lung treated (only if randomised to PDT arm)

10. Ability to give informed consent including the donation of biological samples fortranslational research

Exclusion criteria:

1. PRE-RANDOMISATION: Finding of (micro)-invasive disease on histology

2. HGLs present for ≥5 years which have remained stable on autofluorescence bronchoscopy (AFB) surveillance

3. Detection of active cancer or on systemic treatment for cancer, excluding basal cellskin cancers (unless adjacent to the illumination site)

4. Previous radiotherapy to the central airways

5. ECOG Performance Score >2

6. Patients who are anticoagulated for prosthetic heart valves

7. Decompensated heart disease with life expectancy less than 3 years

8. Severe liver and renal insufficiency with life expectancy less than 3 years

9. Porphyria or hypersensitivity against porphyrins or photosensitivity

10. Hypersensitivity to chlorine-e6-trisodium salt or therapy with anotherphotosensitising agent or relevant antibiotics (macrolides) in the last 4 weeks

11. Ophthalmic disease likely to require slit-lamp examination within 60 days ofregistration/randomisation

12. Planned surgical procedure within 60 days of registration/randomisation

13. Patient unlikely to cooperate with a 3-year follow-up; medical or psychologicalcondition at the discretion of the investigator which would not permit compliance withthe protocol or meaningful signed informed consent

14. Participation in another study with an investigational medicinal product within onemonth prior to registration/randomisation

15. Pregnant or breast feeding women (confirmed by serum/urine ß‐HCG)

16. Any other condition which is assessed as an intolerable risk by the investigator uponinclusion in the study