Non-melanoma Skin Cancer
Conditions
Brief summary
This study aims to examine whether the pain of topical photodynamic therapy (PDT) is significantly different when using low irradiance ambulatory light emitting diode (LED) devices compared with conventional higher irradiance hospital based LED light sources when used for superficial non-melanoma skin cancer. The investigators are also investigating the phototoxicity and efficacy of each regime in this randomized assessor-blinded clinical trial.
Detailed description
A randomized assessor-blinded comparative study of low irradiance ambulatory LED devices with conventional hospital-based LED devices for superficial non-melanoma skin cancer. Preliminary observations suggest that low irradiance LEDs cause less pain but are as effective, so the investigators are examining this in a clinical trial of patients with lesions \</= 2cm diameter of non-melanoma skin cancer (Bowen's disease and superficial basal cell carcinoma). Patients with these conditions referred to the PDT clinic will be invited to participate and if they are eligible and consent to treatment then they will be prospectively randomized to either ambulatory PDT or conventional PDT. Pain and phototoxicity scores will be recorded and clinical efficacy will be assessed up to one year after the last treatment. Computer-generated block randomization will be performed and at 90% power to detect as significant at the 5% level a mean difference in pain score of 2 in one group compared with 4 in the other, 36 patients will be needed, and as the participants will often be elderly and frail the investigators will aim for a safety margin of recruiting 50 participants to account for drop-outs. Participants will receive two treatments of either arm at a one week interval and will be assessed clinically at three months and if residual disease remains then the two treatments a week apart are repeated. Pain assessed using a visual analogue scale (VAS) score and phototoxicity on a semi-quantitative scale are recorded at 7 days when the participant returns for their second treatment. Follow up for clinical assessment is at 6 months and one year after treatment. Participants also give their opinion of treatment at one year follow up. Assessors of adverse effects and efficacy will be blinded. Data recording and analysis will be undertaken by the study statistician Dr Robert Dawe and analysis will be on an intention to treat basis using appropriate statistical tests comparing the pre-planned outcome measures, with pain as primary outcome and outcome, efficacy and patient satisfaction as secondary outcomes
Interventions
DEVICEAmbulight (Ambicare Health)
battery-operated low irradiance red light LED (skin cancer plaster)
Sponsors
Sally Ibbotson
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Bowen's disease or superficial basal cell carcinoma referred for PDT and lesion not greater than 2.4cm diameter
Exclusion criteria
* Unable to give consent, \>2cm diameter, lesions on highly curved surfaces where ambulatory device would not adhere
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain on VAS Score | one week after treatment | assess on visual analogue scale (VAS) score of 0 - 10cm, with 0 representing no pain experienced through to 10 representing the worst pain imaginable. The participant marks across a 0-10cm unmarked line where their level of pain experience is and this is measured eg. 2cm if experiencing mild pain or 8.5cm which would represent severe pain |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phototoxicity | one week after treatment | erythema, oedema, blistering, crusting, ulceration on semi-quantitative scale. Erythema is graded as 0 = absent, 1 = mild, 2 = moderate or 3 = severe erythema as assessed by naked eye examination. Oedema is graded as 0 = absent or 1 = present. Likewise crusting or ulceration are each graded as 0 = absent and 1 = present by naked eye examination. Data will be presented and analysed separately ie. erythema data will be presented and then separately whether oedema, crusting or ulceration are present or absent. ie. reporting may appear as example: erythema score 3 of range of 0-3 options; oedema score 1 (binary option of 0 or 1); crusting score 0 (binary option of 0 or 1); ulceration score 0 (binary option of 0 or 1) |
| Clinical Clearance of Lesion | 12 months after treatment | clinical assessment by study dermatologist to determine by inspection and palpation whether the lesion is clear, partially clear or not clear - assessed at 3, 6 and 12 months after treatment, with 12 months as the final study outcome endpoint analysed |
| Patient Satisfaction | one year after treatment - last visit | brief patient questionnaire to evaluate their opinion of the treatment they received. This is assessed as A.efficacy of treatment - 1 = not effective NR; 2 = partIally effective PR; 3 = completely effective CR; B.Side effects of treatment eg. pain and inflammation - 1 = severe; 2 = moderate; 3 = mild; 4 = none/minimal. C.Practicalities of treatment eg. ease of use, travel, time, inconvenience - 1 = very disruptive and difficult; 2 = moderately disruptive and difficult; 3 = minimally disruptive and difficult. The scores of A, B and C will be added to give an overall score with range of overall minimum score option 3 and maximum 10. Patients will also separately be asked to give overall evaluation on a VAS scale of 0 = treatment very poor and would not have again through to 10 = treatment excellent and I would have again - with a continuous line option from 0 - 10 to mark across, providing a separate score with range options 0 to 10 |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Low Irradiance LED PDT Ambulight LED portable PDT treatment
Ambulight (Ambicare Health): battery-operated low irradiance red light LED (skin cancer plaster) | 32 |
| Conventional Higher Irradiance LED Conventional LED hospital based standard PDT treatment
Ambulight (Ambicare Health): battery-operated low irradiance red light LED (skin cancer plaster) | 18 |
| Total | 50 |
Baseline characteristics
| Characteristic | Conventional Higher Irradiance LED | Total | Low Irradiance LED PDT |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 16 Participants | 38 Participants | 22 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 12 Participants | 10 Participants |
| Age, Continuous | 71 years | 71 years | 75 years |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United Kingdom | 18 participants | 52 participants | 34 participants |
| Sex: Female, Male Female | 12 Participants | 35 Participants | 23 Participants |
| Sex: Female, Male Male | 6 Participants | 15 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 18 |
| other Total, other adverse events | 0 / 32 | 0 / 18 |
| serious Total, serious adverse events | 0 / 32 | 0 / 18 |
Outcome results
Primary
Pain on VAS Score
assess on visual analogue scale (VAS) score of 0 - 10cm, with 0 representing no pain experienced through to 10 representing the worst pain imaginable. The participant marks across a 0-10cm unmarked line where their level of pain experience is and this is measured eg. 2cm if experiencing mild pain or 8.5cm which would represent severe pain
Time frame: one week after treatment
Population: The ambulatory devices suffered technical failure in the first two participants so no data were available for these subjects. Data were available for 32 participants treated with ambulatory PDT and 18 treated with conventional PDT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low Irradiance LED PDT | Pain on VAS Score | 2.95 score on a scale |
| Conventional Higher Irradiance LED | Pain on VAS Score | 1.25 score on a scale |
Comparison: Sample size requirement estimation - Preliminary data showed pain scores of 1.25 with ambulatory PDT (n=12) and 5.26 (SD 2.38) for conventional PDT (n=50). Estimated that for 85% power to detect as significant at 5% level a difference in mean pain score in one group of 2cm compared with 4 cm in the other group, assuming two-sided testing, a minimum of 45 subjects needed. We aimed for 50 subjects, with an allocation ratio of 2 (twice as many randomised to ambulatory PDT as conventional PDT)p-value: <0.0595% CI: [0.71, 2.54]t-test, 2 sided
Secondary
Clinical Clearance of Lesion
clinical assessment by study dermatologist to determine by inspection and palpation whether the lesion is clear, partially clear or not clear - assessed at 3, 6 and 12 months after treatment, with 12 months as the final study outcome endpoint analysed
Time frame: 12 months after treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Irradiance LED PDT | Clinical Clearance of Lesion | 27 Participants |
| Conventional Higher Irradiance LED | Clinical Clearance of Lesion | 14 Participants |
Secondary
Patient Satisfaction
brief patient questionnaire to evaluate their opinion of the treatment they received. This is assessed as A.efficacy of treatment - 1 = not effective NR; 2 = partIally effective PR; 3 = completely effective CR; B.Side effects of treatment eg. pain and inflammation - 1 = severe; 2 = moderate; 3 = mild; 4 = none/minimal. C.Practicalities of treatment eg. ease of use, travel, time, inconvenience - 1 = very disruptive and difficult; 2 = moderately disruptive and difficult; 3 = minimally disruptive and difficult. The scores of A, B and C will be added to give an overall score with range of overall minimum score option 3 and maximum 10. Patients will also separately be asked to give overall evaluation on a VAS scale of 0 = treatment very poor and would not have again through to 10 = treatment excellent and I would have again - with a continuous line option from 0 - 10 to mark across, providing a separate score with range options 0 to 10
Time frame: one year after treatment - last visit
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low Irradiance LED PDT | Patient Satisfaction | 10 score on a scale |
| Conventional Higher Irradiance LED | Patient Satisfaction | 10 score on a scale |
p-value: <0.05Wilcoxon (Mann-Whitney)
Secondary
Phototoxicity
erythema, oedema, blistering, crusting, ulceration on semi-quantitative scale. Erythema is graded as 0 = absent, 1 = mild, 2 = moderate or 3 = severe erythema as assessed by naked eye examination. Oedema is graded as 0 = absent or 1 = present. Likewise crusting or ulceration are each graded as 0 = absent and 1 = present by naked eye examination. Data will be presented and analysed separately ie. erythema data will be presented and then separately whether oedema, crusting or ulceration are present or absent. ie. reporting may appear as example: erythema score 3 of range of 0-3 options; oedema score 1 (binary option of 0 or 1); crusting score 0 (binary option of 0 or 1); ulceration score 0 (binary option of 0 or 1)
Time frame: one week after treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low Irradiance LED PDT | Phototoxicity | 2 score on a scale |
| Conventional Higher Irradiance LED | Phototoxicity | 1 score on a scale |