Randomized Comparison of Low and Conventional Irradiance PDT for Skin Cancer

• Sponsor: Sally Ibbotson (Other)
• Overall Status: Completed
• CT.gov ID: NCT02872909
• Collaborator: (none)
• Enrollment: 50
• Arms: 2
• Duration (Months): 64.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-melanoma Skin Cancer	Device: Ambulight (Ambicare Health)	N/A

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized Assessor-blinded Comparison of Low Irradiance and Conventional Irradiance Photodynamic Therapy (PDT) for Superficial Non-melanoma Skin Cancer
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Feb 6, 2017
• Actual Study Completion Date: Feb 6, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: low irradiance LED PDT Ambulight LED portable PDT treatment	Device: Ambulight (Ambicare Health); battery-operated low irradiance red light LED ("skin cancer plaster")
Active Comparator: conventional higher irradiance LED Conventional LED hospital based standard PDT treatment	Device: Ambulight (Ambicare Health); battery-operated low irradiance red light LED ("skin cancer plaster")

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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)

2. 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

3. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Sally Ibbotson

Investigators

• Principal Investigator: Sally H Ibbotson, MD, University of Dundee

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 2, 2012

More Information

Publications

• Attili SK, Lesar A, McNeill A, Camacho-Lopez M, Moseley H, Ibbotson S, Samuel ID, Ferguson J. An open pilot study of ambulatory photodynamic therapy using a wearable low-irradiance organic light-emitting diode light source in the treatment of nonmelanoma skin cancer. Br J Dermatol. 2009 Jul;161(1):170-3. doi: 10.1111/j.1365-2133.2009.09096.x. Epub 2009 Mar 19.
• Ibbotson SH, Ferguson J. Ambulatory photodynamic therapy using low irradiance inorganic light-emitting diodes for the treatment of non-melanoma skin cancer: an open study. Photodermatol Photoimmunol Photomed. 2012 Oct;28(5):235-9. doi: 10.1111/j.1600-0781.2012.00681.x.
• Ibbotson SH. Irradiance is an important determinant of pain experienced during topical photodynamic therapy. J Am Acad Dermatol. 2011 Jul;65(1):201-2. doi: 10.1016/j.jaad.2010.11.060.
• Moseley H, Allen JW, Ibbotson S, Lesar A, McNeill A, Camacho-Lopez MA, Samuel ID, Sibbett W, Ferguson J. Ambulatory photodynamic therapy: a new concept in delivering photodynamic therapy. Br J Dermatol. 2006 Apr;154(4):747-50.

• Responsible Party: Sally Ibbotson, Dr Sally H Ibbotson, University of Dundee
• ClinicalTrials.gov Identifier: NCT02872909
• Other Study ID Numbers: 2011DS04
• First Posted: Aug 19, 2016
• Last Update Posted: Jan 4, 2019
• Last Verified: Dec 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Skin Neoplasms

Study Results

Participant Flow

Arm/Group Title	Low Irradiance LED PDT	Conventional Higher Irradiance LED
Arm/Group Description	Ambulight LED portable PDT treatment Ambulight (Ambicare Health): battery-operated low irradiance red light LED ("skin cancer plaster")	Conventional LED hospital based standard PDT treatment Ambulight (Ambicare Health): battery-operated low irradiance red light LED ("skin cancer plaster")
Period Title: Overall Study
STARTED	32	18
COMPLETED	32	18
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Low Irradiance LED PDT	Conventional Higher Irradiance LED	Total
Arm/Group Description	Ambulight LED portable PDT treatment Ambulight (Ambicare Health): battery-operated low irradiance red light LED ("skin cancer plaster")	Conventional LED hospital based standard PDT treatment Ambulight (Ambicare Health): battery-operated low irradiance red light LED ("skin cancer plaster")	Total of all reporting groups
Overall Participants	32	18	50
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	10 31.3%	2 11.1%	12 24%
>=65 years	22 68.8%	16 88.9%	38 76%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	75	71	71
Sex: Female, Male (Count of Participants)
Female	23 71.9%	12 66.7%	35 70%
Male	9 28.1%	6 33.3%	15 30%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United Kingdom	34 106.3%	18 100%	52 104%

Outcome Measures

1. Primary Outcome

Title	Pain on VAS Score
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Low Irradiance LED PDT	Conventional Higher Irradiance LED
Arm/Group Description	Ambulight LED portable PDT treatment Ambulight (Ambicare Health): battery-operated low irradiance red light LED ("skin cancer plaster")	Conventional LED hospital based standard PDT treatment Ambulight (Ambicare Health): battery-operated low irradiance red light LED ("skin cancer plaster")
Measure Participants	32	18
Median (Inter-Quartile Range) [score on a scale]	2.95	1.25

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Low Irradiance LED PDT, Conventional Higher Irradiance LED
	Comments	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)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments	calculated as <0.05 for 85% power
	Method	t-test, 2 sided
	Comments	Analysed on log transformed data
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.37
	Confidence Interval	(2-Sided) 95%; 0.71 to 2.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Phototoxicity
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Irradiance LED PDT	Conventional Higher Irradiance LED
Arm/Group Description	Ambulight LED portable PDT treatment Ambulight (Ambicare Health): battery-operated low irradiance red light LED ("skin cancer plaster")	Conventional LED hospital based standard PDT treatment Ambulight (Ambicare Health): battery-operated low irradiance red light LED ("skin cancer plaster")
Measure Participants	32	18
Median (Full Range) [score on a scale]	2	1

3. Secondary Outcome

Title	Clinical Clearance of Lesion
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Irradiance LED PDT	Conventional Higher Irradiance LED
Arm/Group Description	Ambulight LED portable PDT treatment Ambulight (Ambicare Health): battery-operated low irradiance red light LED ("skin cancer plaster")	Conventional LED hospital based standard PDT treatment Ambulight (Ambicare Health): battery-operated low irradiance red light LED ("skin cancer plaster")
Measure Participants	32	18
Count of Participants [Participants]	27 84.4%	14 77.8%

4. Secondary Outcome

Title	Patient Satisfaction
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Irradiance LED PDT	Conventional Higher Irradiance LED
Arm/Group Description	Ambulight LED portable PDT treatment Ambulight (Ambicare Health): battery-operated low irradiance red light LED ("skin cancer plaster")	Conventional LED hospital based standard PDT treatment Ambulight (Ambicare Health): battery-operated low irradiance red light LED ("skin cancer plaster")
Measure Participants	32	18
Median (Full Range) [score on a scale]	10	10

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Low Irradiance LED PDT, Conventional Higher Irradiance LED
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	Up to 1 year follow up visit for each participant
Arm/Group Title	Low Irradiance LED PDT		Conventional Higher Irradiance LED
Arm/Group Description	Ambulight LED portable PDT treatment Ambulight (Ambicare Health): battery-operated low irradiance red light LED ("skin cancer plaster")		Conventional LED hospital based standard PDT treatment Ambulight (Ambicare Health): battery-operated low irradiance red light LED ("skin cancer plaster")
All Cause Mortality
	Low Irradiance LED PDT		Conventional Higher Irradiance LED
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/32 (0%)		0/18 (0%)
Serious Adverse Events
	Low Irradiance LED PDT		Conventional Higher Irradiance LED
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/32 (0%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	Low Irradiance LED PDT		Conventional Higher Irradiance LED
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/32 (0%)		0/18 (0%)

Limitations/Caveats

Nil of note

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.