Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

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Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Dermatologic Agents

All Drugs and Chemicals

Photosensitizing Agents

Patients randomised to the PDT treatment (Intervention Arm) will have two courses of PDT treatment in total (for each lung treated). Follow-up is the same as for Control Arm patients: an AFB at 6, 12, 24, and at 36 months post-randomisation; with further AFB visits at 18 and/or at 30 months post-randomisation (dependent on lesion appearance).

Patients randomised to the surveillance (Control Arm) will have: an AFB at 6, 12, 24, and at 36 months post-randomisation; with further AFB visits at 18 and/or at 30 months post-randomisation (dependent on lesion appearance).

Photodynamic Therapy (PDT) using photosensitiser drug Fotolon

Photodynamic Therapy (PDT)

PEARL is a phase III multicentre 2:1 randomised controlled trial, with an incorporated phase II (pilot) component. All patients consented/registered onto the trial will have an autofluorescence bronchoscopy (AFB) to check for the presence of high grade lesions (HGLs) in the lung, as verified by tissue biopsy. Only patients with one or more histologically confirmed lung HGL will be randomised to receive either photodynamic therapy (PDT) treatment with surveillance (=intervention), or surveillance alone (=control).

The overall aim of the phase II pilot is to demonstrate a \>20% response in the PDT group (at least 3 out of 21 PDT patients), compared to a minimum response of 5%. This will be used as an efficacy signal to determine whether the trial will continue into phase III. Response will be measured by regression of high grade lesions (HGLs) to either low grade lesions (LGLs), or to normal epithelium at 6 months post treatment (blind assessment). The overall aim of the phase III is to show that the time period over which HGLs progress to invasive lung cancer is significantly longer when treated with PDT compared to surveillance alone.

Background: Squamous cell carcinoma of the lung develops through a transition of progressive cytological aberration, from normal to metaplasia, mild, moderate, and severe dysplasia and then carcinoma in situ (CIS) before becoming an invasive cancer. Progression rates to invasive carcinoma can vary depending on the initial grade of lesion and it is generally accepted that high-grade lesions are more likely to progress to invasive cancer than low-grade lesions. Early detection and treatment of these lesions is critical to improving survival. There is no evidence base examining how, or whether these high-grade lesions (HGLs) should be treated, resulting in diverse treatment practices both nationally and internationally. This is the first randomised clinical trial of a bronchoscopic intervention in treating HGLs using PDT.

Treatment: Treatment-arm patients will receive two courses of PDT treatment using the photosensitiser drug Fotolon®. Fotolon®, which preferentially accumulates in HGLs, is first administered via IV infusion. Patients then undergo bronchoscopy during which their HGLs are irradiated with red light (via non-heat emitting laser). Red-light activation of the photosensitiser causes chemical transformation of the cells and cell death.

Follow Up: Follow up in both arms consists of AFB surveillance at 6 and 12 months, then every 6-12 months (depending on the appearance of lesions), with annual CT scanning of the thorax, and annual spirometry. Biological samples for translational analysis will be taken at baseline and each subsequent trial visit.

Duration of recruitment: Anticipated recruitment for phase II is 1 year (12 months), and an additional 2 years (24 months) for the phase III.

Photodynamic Therapy for the Prevention of Lung Cancer

Photodynamic Therapy for the Prevention of Lung Cancer (PEARL)

of high grade lesions in the lung to invasive lung cancer; compared between the PDT and control groups

(regression, stable appearance, progession or recurrence) of HGLs present at baseline (index lesions); compared between the PDT and control groups

HGLs identified post-baseline at new sites within the lung (i.e. not at the site of the index lesions); compared between the PDT and control groups

that develop at remote sites within the lung in both arms

as detected on bronchoscopy and CT thorax in patients harbouring HGLs from date of randomisation; compared between the PDT and control groups

from date of randomisation; compared between the PDT and control groups

to determine whether PDT affects spirometry

Based on the maximum toxicity grade for each patient for each event type; compared between the PDT and control groups

University College, London

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Recurrence

Head and Neck Neoplasms

Skin Neoplasms

Skin Diseases

Antineoplastic Agents

Anti-Infective Agents

Bleomycin

Anti-Bacterial Agents

Antibiotics, Antitubercular

No comparative treatment is given in this open-label phase I, dose escalating safety study

intravenous TPCS2a, followed by standard dose of bleomycin (iv infusion) and illumination with CeramOptec laser.

Amphinex (TPCS2a)

Illumination with CeramOptec laser

Colin Hopper, MD

This study is an open, non- randomized, phase I, dose-escalating study to evaluate the safety and tolerance of Amphinex based PCI of bleomycin in patients with local recurrent or advanced/metastatic, cutaneous or sub-cutaneous malignancies.

Eligible patients will be included in cohorts of 3 patients. The initial starting dose for Amphinex will be given 4 days prior to the fixed dose of bleomycin administered by intravenous infusion. The illumination, with red light (laser 652 nm), to the tumour surface and a margin of 2-3 mm outside the tumour surface, will be performed after bleomycin administration.

There will be no comparative procedure in this study. Dose escalation will proceed according to a modification of Simon's accelerated titration design. The number of patients recruited depends on the DLT experienced. A total of 6 patients will be included at each dose level if no more than 1 patient experiences DLT.

Additional cohorts may be added pending the outcome of the previous cohorts and discussions between the investigators and the Sponsor. The primary goal of the study is to assess the safety and tolerance of the Amphinex and determine the maximal tolerated dose (MTD) of Amphinex as a PCI therapy in combination with bleomycin treatment.

Safety Study of Amphinex Based Photochemical Internalisation (PCI) of Bleomycin in Patients With Cutaneous Cancer

Phase I, Dose-escalating Study to Evaluate Safety and Tolerance of Amphinex Based Photochemical Internalisation (PCI) of Bleomycin in Patients With Local Recurrence or Advanced/Metastatic, Cutaneous or Sub-cutaneous Malignancies

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Photodynamic Therapy for the Prevention of Lung Cancer	NCT03346304	Squamous Cell L... Lung Cancer	Photodynamic Th...	18 Years -	University College, London
Photodynamic Therapy for the Prevention of Lung Cancer	NCT03346304	Squamous Cell L... Lung Cancer	Photodynamic Th...	18 Years -	University College, London
Photodynamic Therapy for the Prevention of Lung Cancer	NCT03346304	Squamous Cell L... Lung Cancer	Photodynamic Th...	18 Years -	University College, London
Photodynamic Therapy for the Prevention of Lung Cancer	NCT03346304	Squamous Cell L... Lung Cancer	Photodynamic Th...	18 Years -	University College, London
Safety Study of Amphinex Based Photochemical Internalisation (PCI) of Bleomycin in Patients With Cutaneous Cancer	NCT00993512	Head and Neck N... Skin Neoplasms	Amphinex (TPCS2... Bleomycin Illumination wi...	18 Years -	PCI Biotech AS

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