Squamous Cell Lung CancerPhase 2/3PEARLNCT03346304
Photodynamic Therapy for the Prevention of Lung Cancer
A Phase 2/3 study testing Photodynamic Therapy (PDT) in people with Squamous Cell Lung Cancer and Lung Cancer, run by University College, London.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Squamous Cell Lung Cancer, Lung Cancer
- What is being tested?
- Photodynamic Therapy (PDT)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Sep 2018to Oct 2024
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with ≥1 histologically confirmed lung HGL (defined as severe dysplasia or carcinoma in situ) PRE-REGISTRATION: High likelihood of presence of lung HGLs as evaluated by investigator (e.g. because patient part of existing surveillance cohort or referred to trial site) and inclusion/exclusion criteria below. PRE-RANDOMISATION: Following registration and AFB, only patients with ≥1 lung HGLs confirmed histologically can be continue to randomisation provided they continue to meet inclusion/exclusion criteria below.
- Absence of metastatic disease or other primary cancers as confirmed by CT thorax within 28 days prior to registration only)
- Male or female patients ≥18 years of age
- No upper age limit but life expectancy must be at least 3 years
- ECOG Performance Score 0-2
- FEV1 ≥ 25% of predicted
Show all 13Show fewer
- DLCO/TLCO ≥ 20% of predicted (within 28 days prior to registration only)
- Women of child-bearing potential (WOCBP), or men with female partners who are pregnant or WOCBP must be willing to practise highly effective methods of birth control starting as soon as possible from the time of informed consent and registration until randomisation (if randomised to the control arm), or until 3 months after the end of their last PDT treatment (if randomised to the intervention arm) . Male patients must also advise their female partners who are WOCBP regarding contraceptive requirements as listed for female patients who are WOCBP.
- Patients who are WOCBP must also have a negative pregnancy test at the following time points:
- 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)
- Ability to give informed consent including the donation of biological samples for translational research
Who cannot join
- PRE-RANDOMISATION: Finding of (micro)-invasive disease on histology
- HGLs present for ≥5 years which have remained stable on autofluorescence bronchoscopy (AFB) surveillance
- Detection of active cancer or on systemic treatment for cancer, excluding basal cell skin cancers (unless adjacent to the illumination site)
- Previous radiotherapy to the central airways
- ECOG Performance Score >2
- Patients who are anticoagulated for prosthetic heart valves
Show all 16Show fewer
- Decompensated heart disease with life expectancy less than 3 years
- Severe liver and renal insufficiency with life expectancy less than 3 years
- Porphyria or hypersensitivity against porphyrins or photosensitivity
- Hypersensitivity to chlorine-e6-trisodium salt or therapy with another photosensitising agent or relevant antibiotics (macrolides) in the last 4 weeks
- Ophthalmic disease likely to require slit-lamp examination within 60 days of registration/randomisation
- Planned surgical procedure within 60 days of registration/randomisation
- Patient unlikely to cooperate with a 3-year follow-up; medical or psychological condition at the discretion of the investigator which would not permit compliance with the protocol or meaningful signed informed consent
- Participation in another study with an investigational medicinal product within one month prior to registration/randomisation
- Pregnant or breast feeding women (confirmed by serum/urine ß-HCG)
- Any other condition which is assessed as an intolerable risk by the investigator upon inclusion in the study
About this study
Official title: Photodynamic Therapy for the Prevention of Lung Cancer (PEARL)
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.
Read the detailed description
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.
- Conditions
- Squamous Cell Lung Cancer, Lung Cancer
- Being tested
- Photodynamic Therapy (PDT)
- Keywords
- Autofluorescence Broncoscopy (AFB), Photodynamic Therapy (PDT), High Grade Lesions (HGLs), lung cancer, photosensitiser, Fotolon
- Medical subject headings
- Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Photodynamic Therapy (PDT)Other
Photodynamic Therapy (PDT) using photosensitiser drug Fotolon
| Study group | Role | What they receive |
|---|---|---|
| PDT treatment (Intervention Arm) | Experimental | 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). Receives: Other: Photodynamic Therapy (PDT) |
| Surveillance (Control Arm) | No intervention | 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). |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to site-specific progression
of high grade lesions in the lung to invasive lung cancer; compared between the PDT and control groups
Measured: within a 3-year follow-up (incorporates patients from phase II)
Secondary outcomes (10)
Site-specific response
(regression, stable appearance, progession or recurrence) of HGLs present at baseline (index lesions); compared between the PDT and control groups
Measured: within a 3-year follow-up (incorporates patients from phase II)
Number of new HGLs
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
Measured: within a 3-year follow-up (incorporates patients from phase II)
Number of metachronous endobronchial lung cancers
that develop at remote sites within the lung in both arms
Measured: within a 3-year follow-up (incorporates patients from phase II)
Cumulative risk of developing lung cancer
as detected on bronchoscopy and CT thorax in patients harbouring HGLs from date of randomisation; compared between the PDT and control groups
Measured: within a 3-year follow-up (incorporates patients from phase II)
Overall and cancer specific survival
from date of randomisation; compared between the PDT and control groups
Measured: within a 3-year follow-up (incorporates patients from phase II)
Difference in spirometry (FEV1, FVC) values
to determine whether PDT affects spirometry
Measured: at specific time points (6,12,24 and 36 months post randomisation);
Adverse events
Based on the maximum toxicity grade for each patient for each event type; compared between the PDT and control groups
Measured: within a 3-year follow-up (incorporates patients from phase II)
EQ-5D-5L
Health-Related Quality of Life (HRQoL)
Measured: at specific time points (6,12,24 and 36 months, and possibly 18 and 30 months, post randomisation); compared between the PDT and control groups
EORTC QLQ-LC13
Health-Related Quality of Life (HRQoL)
Measured: at specific time points (6,12,24 and 36 months, and possibly 18 and 30 months, post randomisation); compared between the PDT and control groups
ACE-27
Health-Related Quality of Life (HRQoL)
Measured: at specific time points (6,12,24 and 36 months, and possibly 18 and 30 months, post randomisation); compared between the PDT and control groups
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2017
- Study startSep 2018 (estimated)
- Primary completionSep 2024 (estimated)
- Study completionOct 2024 (estimated)
Why it stopped: drug no longer available
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Squamous Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03346304
- Sponsor's protocol ID
- UCL/13/0390
- Acronym
- PEARL
- Status last verified
- Jan 2019
- First submitted
- 9 Nov 2017
- Last updated
- 1 Feb 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Photodynamic Therapy for the Prevention of Lung Cancer (PEARL)
- ClinicalTrials.gov ID
- NCT03346304
- Acronym / sponsor ID
- PEARL / UCL/13/0390
- Conditions
- Squamous Cell Lung Cancer, Lung Cancer
- Keywords
- Autofluorescence Broncoscopy (AFB), Photodynamic Therapy (PDT), High Grade Lesions (HGLs), lung cancer, photosensitiser, Fotolon
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: drug no longer available
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Study start
- Sep 2018 (estimated)
- Primary completion
- Sep 2024 (estimated)
- Study completion
- Oct 2024 (estimated)
- First posted
- 17 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PDT treatment (Intervention Arm) | Experimental | Other: Photodynamic Therapy (PDT)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). |
| Surveillance (Control Arm) | No intervention | –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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients with ≥1 histologically confirmed lung HGL (defined as severe dysplasia or carcinoma in situ) PRE-REGISTRATION: High likelihood of presence of lung HGLs as evaluated by investigator (e.g. because patient part of existing surveillance cohort or referred to trial site) and inclusion/exclusion criteria below. PRE-RANDOMISATION: Following registration and AFB, only patients with ≥1 lung HGLs confirmed histologically can be continue to randomisation provided they continue to meet inclusion/exclusion criteria below.
- Absence of metastatic disease or other primary cancers as confirmed by CT thorax within 28 days prior to registration only)
- Male or female patients ≥18 years of age
- No upper age limit but life expectancy must be at least 3 years
- ECOG Performance Score 0-2
Key exclusion criteria (16 listed)
- PRE-RANDOMISATION: Finding of (micro)-invasive disease on histology
- HGLs present for ≥5 years which have remained stable on autofluorescence bronchoscopy (AFB) surveillance
- Detection of active cancer or on systemic treatment for cancer, excluding basal cell skin cancers (unless adjacent to the illumination site)
- Previous radiotherapy to the central airways
- ECOG Performance Score >2
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Photodynamic Therapy (PDT)Photodynamic Therapy (PDT) using photosensitiser drug Fotolon | Other | PDT treatment (Intervention Arm) |
Primary outcome
Time to site-specific progression
Time frame: within a 3-year follow-up (incorporates patients from phase II)
of high grade lesions in the lung to invasive lung cancer; compared between the PDT and control groups
10 secondary outcomes
Site-specific response
Time frame: within a 3-year follow-up (incorporates patients from phase II)
Number of new HGLs
Time frame: within a 3-year follow-up (incorporates patients from phase II)
Number of metachronous endobronchial lung cancers
Time frame: within a 3-year follow-up (incorporates patients from phase II)
Cumulative risk of developing lung cancer
Time frame: within a 3-year follow-up (incorporates patients from phase II)
Overall and cancer specific survival
Time frame: within a 3-year follow-up (incorporates patients from phase II)
Difference in spirometry (FEV1, FVC) values
Time frame: at specific time points (6,12,24 and 36 months post randomisation);
Adverse events
Time frame: within a 3-year follow-up (incorporates patients from phase II)
EQ-5D-5L
Time frame: at specific time points (6,12,24 and 36 months, and possibly 18 and 30 months, post randomisation); compared between the PDT and control groups
EORTC QLQ-LC13
Time frame: at specific time points (6,12,24 and 36 months, and possibly 18 and 30 months, post randomisation); compared between the PDT and control groups
ACE-27
Time frame: at specific time points (6,12,24 and 36 months, and possibly 18 and 30 months, post randomisation); compared between the PDT and control groups
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Photodynamic Therapy (PDT) in people with Squamous Cell Lung Cancer and Lung Cancer, run by University College, London.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 1 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to site-specific progression (time frame: within a 3-year follow-up (incorporates patients from phase II)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2019.