Microwave Therapy for Treatment of Precancerous Actinic Keratoses
Phase: NA
Conditions: Actinic Keratoses, Precancerous Skin Lesion
Sponsor: University of Dundee

1 
 
 
Trial Protocol 
Microwave therapy for treatment of precancerous actinic keratoses 
 
Trial Acronym 
MTAK 
Sponsor 
University of Dundee NHS Tayside 
Sponsor R&D Number 
2016DS12 
Funder 
Innovate UK 
Chief Investigator 
Prof Charlotte Proby 
REC Number 
18/ES/0008 
Clinical Trials Unit  
Tayside Clinical Trials Unit 
Clinicaltrials.gov Number 
NCT03483935 
Version Number and Date 
Version   5 26/09/2018 
 

MTAK protocol v5 26-09-2018 
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PROTOCOL APPROVAL .......................................................................................................... 4 
LIST OF ABBREVIATIONS ....................................................................................................... 5 
1 
INTRODUCTION ......................................................................................................... 7 
1.1 
BACKGROUND ................................................................................................ 7 
1.2 
Rationale ........................................................................................................... 7 
2 
STUDY OBJECTIVES & OUTCOMES ....................................................................... 8 
3 
STUDY DESIGN ......................................................................................................... 9 
3.1 
study Description .............................................................................................. 9 
3.2 
Intervention .....................................................................................................11 
3.3 
STUDY FLOWCHART ....................................................................................11 
3.4 
STUDY MATRIX .............................................................................................11 
3.5 
STUDY ASSESSMENTS ................................................................................11 
3.6 
STUDY safety ASSESSMENTS .....................................................................11 
3.6.1 
Physical examination ............................................................................11 
3.6.2 
Hearing Aids .........................................................................................11 
3.6.3 
Visual examination ...............................................................................12 
3.6.4 
Potential discomfort and skin biopsy procedure ...................................12 
3.7 
TISSUE ...........................................................................................................12 
3.8 
INCIDENTAL FINDINGS ................................................................................12 
3.9 
study POPULATION .......................................................................................12 
3.10 
NUMBER OF PARTICIPANTS .......................................................................12 
3.11 
INCLUSION CRITERIA...................................................................................12 
3.12 
EXCLUSION CRITERIA .................................................................................13 
4 
PARTICIPANT SELECTION AND ENROLMENT....................................................13 
4.1 
IDENTIFYING PARTICIPANTS ......................................................................13 
4.2 
CONSENTING PARTICIPANTS .....................................................................13 
4.3 
SCREENING FOR ELIGIBILITY .....................................................................14 
4.4 
INELIGIBLE AND NON-RECRUITED PARTICIPANTS .................................14 
4.5 
RANDOMISATION ..........................................................................................14 
4.5.1 
Randomisation ......................................................................................14 
4.5.2 
Intervention Allocation ..........................................................................14 
4.5.3 
Withdrawal procedures .........................................................................14 
5 
DATA COLLECTION & MANAGEMENT .................................................................15 
5.1 
Data Collection ................................................................................................15 
5.2 
Data Management System .............................................................................15 
6 
STATISTICS AND DATA ANALYSIS ......................................................................15 
6.1 
SAMPLE SIZE CALCULATION ......................................................................15 
6.2 
PROPOSED ANALYSES ...............................................................................16 
6.3 
Missing data ....................................................................................................16 
6.4 
TRANSFER OF DATA ....................................................................................16 
7 
STUDY MANAGEMENT AND OVERSIGHT ARRANGEMENTS ............................16 
7.1 
STUDY MANAGEMENT GROUP ...................................................................16 
7.2 
STUDY STEERING COMMITTEE ..................................................................17 
7.3 
DATA MONITORING COMMITTEE ...............................................................17 
7.4 
INSPECTION OF RECORDS .........................................................................17 
8 
GOOD CLINICAL PRACTICE ..................................................................................17 
8.1 
ETHICAL CONDUCT OF THE STUDY ..........................................................17 
8.2 
Confidentiality .................................................................................................17 
8.3 
Data Protection ...............................................................................................17 
8.4 
Insurance and Indemnity ................................................................................17 
9 
ADVERSE EVENTS .................................................................................................18 
9.1 
DEFINITIONS .................................................................................................18 
9.2 
RECORDING AND REPORTING AE .............................................................18 
10 
ANNUAL REPORTING REQUIREMENTS ..............................................................19 
11 
STUDY CONDUCT RESPONSIBILITIES ................................................................19 
11.1 
PROTOCOL AMENDMENTS, deviations and breaches ................................19 
11.2 
STUDY RECORD RETENTION .....................................................................19 
11.3 
END OF STUDY .............................................................................................19 
12 
REPORTING, PUBLICATIONS AND NOTIFICATION OF RESULTS ....................19 
12.1 
AUTHORSHIP POLICY ..................................................................................19 

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12.2 
PUBLICATION ................................................................................................19 
12.3 
PEER REVIEW ...............................................................................................20 
13 
REFERENCES ..........................................................................................................20 
APPENDIX 1: STAGE 1 STUDY FLOWCHART .....................................................................21 
APPENDIX 2: STAGE 1 STUDY MATRIX ..............................................................................22 
APPENDIX 3: STAGE 2 STUDY FLOW CHART ....................................................................23 
APPENDIX 4: STAGE 2 STUDY MATRIX ..............................................................................24 
 
 
 

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PROTOCOL APPROVAL 
Microwave therapy for treatment of precancerous actinic keratoses 
 
Signatures 
The undersigned confirm that the following protocol has been agreed and approved by the Sponsor and 
that the Chief Investigator agrees to conduct the study in compliance with this approved protocol and will 
adhere to the principles of GCP, the Sponsor SOPs, and any other applicable regulatory requirements 
as may be amended from time to time. 
 
Prof Charlotte Proby 
 
 
 
Chief Investigator 
Signature 
 
Date 
 
 
 
 
Prof Peter Donnan 
 
 
 
Individual 
Responsible 
for 
Statistical Review 
Signature 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 

MTAK protocol v5 26-09-2018 
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LIST OF ABBREVIATIONS 
 
 
AE 
Adverse Event 
AK 
Actinic Keratosis 
CI 
Chief Investigator 
CNORIS 
Clinical Negligence and Other Risks Scheme 
CRF 
Case Report Form 
DMC 
Data Monitoring Committee 
GCP 
Good Clinical Practice 
ICF 
Informed Consent Form 
IF 
Incidental Findings 
ISF 
Investigator Site File 
PI 
Principal Investigator 
PIS 
Patient Information Sheet 
REC 
Research Ethics Committee 
SAE 
Serious Adverse Event 
SOP 
Standard Operating Procedures 
TMF 
Trial Master File 
TMG 
Trial Management Group 
TSC 
Trial Steering Committee 
 
 
 

MTAK protocol v5 26-09-2018 
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SUMMARY/SYNOPSIS 
 
Study Title  
Microwave Therapy for treatment of precancerous Actinic Keratosis 
MTAK 
Study Design 
Medical Device trial 
Stage 1: Volunteer study to measure the tissue properties of actinic keratosis 
(AK) prior to microwave therapy.  
Stage 2: RCT  
Study Population 
Adults diagnosed with AK  
Sample Size 
Stage 1: Up to 10  
Stage 2: Up to 12 randomised 
Planned Study Period  
24 months 
Clinical phase duration  
Stage 1: Participants will be in the study for 1 day 
Stage 2: Participants will be in the trial for up to 28 days 
Follow up phase 
duration  
Stage 1: No follow up 
Stage 2: Participants will be followed up for 4 months 
Stage 1 Primary 
Objectives 
To determine the permittivity of 
clinically diagnosed thick and thin AK 
skin lesions on the hand and visible 
scalp using a measurement device. 
Outcome Measures 
Dielectric permittivity measure, also 
known as epsilon relative Er, 
relative to air (Er=1). 
Stage 2 Primary 
 
Objectives 
Evaluate the efficacy of microwave 
with the Swift instrument treatment 
versus no treatment on the resolution 
of AK lesions using visual assessment  
Outcome Measures 
Skin 
examination 
with 
clinical 
assessments 
and 
photographic 
mapping to confirm resolution of AK. 
Stage 2 Secondary 
Objectives 
To evaluate the long-term resolution 
of AK following microwave treatment 
Outcome Measures 
Skin 
examination 
with 
clinical 
assessments 
and 
photographic 
mapping to confirm resolution of AK 
at 2 and 4 months. 
 
Objectives 
To evaluate patient acceptability of 
the use microwave treatment as a 
therapy for AK 
Outcome Measures 
Number of Adverse Events and 
patient acceptability 
 
Objectives 
Identify the potential mode of action of 
microwave energy in the treatment of 
AK 
 
Outcome Measures 
Changes in biomarkers of cell 
proliferation, 
cell 
survival 
and 
cellular stress responses and the 
expression and activity of other 
genes in the biopsy tissue. 
 
 
 

MTAK protocol v5 26-09-2018 
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1 
INTRODUCTION 
1.1 
BACKGROUND  
 
This study is a collaboration between the University of Dundee, NHS Tayside and Emblation Ltd, 
funded by Innovate UK.  Emblation is a Scottish based SME and is an established global leader in the 
design, development and manufacture of microwave medical devices. 
 
Actinic keratoses (AK) are believed the most common pre-cancerous lesions in humans and are 
precursors to invasive cutaneous squamous cell carcinoma (cSCC), a malignancy that has more than 
doubled in incidence in the UK in the last decade due to ageing populations and increased UV 
exposure (Goon 2017).  The UK incidence of cSCC now exceeds 30,000 annually (estimated >50,000 
cases/year, Public Health England, unpublished data) with significant health burden and NHS costs.  
These skin cancers are often multiple, especially in immunosuppressed high-risk populations.  AK are 
very common “sun damage” skin lesions found on sun-exposed areas of the skin, such as the backs of 
hands and bald scalp.  Up to 70% of our elderly population have AK (Eder 2014) and 65% of cSCC 
arise from previously identified AK (Criscione 2009).  AK are readily identified clinically so AK treatment 
offers an important opportunity for cancer prevention, but our ability to treat is limited by undesirable 
local adverse reactions from existing topical treatments which fail to balance effectiveness, side effects 
and cost.  None of the currently available treatments for AK are suitable for widespread use in the 
community and are only partially effective.  Other more effective treatments such as photodynamic 
therapy are expensive and time consuming and need to be delivered by experts in secondary care.  
NHS dermatologists are already overburdened and elderly patients with AK do not wish to travel. AK 
therapy would be greatly improved by a cheap, convenient, well-tolerated and efficacious therapy that 
can be delivered closer to home by GPs or nurses. 
 
Clinically, AK display a spectrum of severity from mild Grade 1 lesions, which are just visible and just 
(barely) palpable, through Grade 2 red and scaly lesions (easily felt and seen), to the most severe 
Grade 3 lesions, which are grossly hyperkeratotic and “thickened” skin lesions.  In practice, it is easier 
to grade them as ‘thin’ (just palpable) or ‘thick’ (with substance to them).  It is possible that the dielectric 
properties of Thick and Thin AK will differ and therefore the measurement study will need to be carried 
out on both types of AK such that the appropriate microwave dose can be given to these variable skin 
lesions.    
 
1.2 
RATIONALE 
Our hypothesis is that localised microwave energy therapy is a suitable treatment for Actinic Keratosis 
(AK) skin lesions.   
 
The use of microwave technology is well established as ablative doses for treatment of malignancy e.g. 
hepatocellular carcinoma (see refs Poggi, Wang, Liang and Martin).  There are no known studies using 
microwave for treatment of pre-cancerous skin conditions or skin cancers.  Furthermore, there is very 
little understanding of the biological process evoked by localised microwave exposure in the skin or of 
the clinically-relevant biological mechanisms triggered.   
 
Emblation already have a CE-marked microwave instrument used successfully for the treatment of 
plantar viral warts, the SWIFT device.  We now wish to undertake a feasibility trial in 12 participants, 
each with multiple AK on dorsal hand skin or bald scalp or both.  The trial will examine the tolerability, 
acceptability, efficacy and long-term resolution of AK following one or more treatments with microwave 
energy delivered using the SWIFT device. 
 
Previous studies performed by Emblation using SWIFT on plantar viral warts found it to be effective and 
safe (Bristow 2017).  Some participants experienced minor discomfort during the microwave therapy but 
any pain stopped when treatment stopped. Some reddening of the skin at the treatment site may occur 
but this resolved after 24 hours. Some instances of a haematoma have been seen at larger doses, 
typically resolving within 7 days.   
 
This will be a two-stage study, stage 1 to measure the electrical properties of AKs in patients. The data 
from stage 1 allows derivation of the power settings to be used with SWIFT for AK in stage 2, to 
conduct a randomised controlled trial of microwave treatment, delivered using SWIFT, versus no 
treatment. 

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The SWIFT device has variable power and duration controls, the protocol suitable for plantar viral warts 
is unlikely to be compatible with AK.  Plantar warts (verrucas) are considerably thicker than AK and are 
located on much thicker, more robust areas of normal skin.  AK are most common in the elderly 
population and are located on thinner, more delicate skin.  We therefore anticipate that AK will require a 
smaller dose of microwave energy than plantar warts.  In order to derive the correct power and duration 
settings for the Swift instrument and impart the correct amount of electromagnetic energy (referred to as 
dose) into the AK, the dielectric properties of AK need to be determined to confirm how the specific 
tissue responds to the electromagnetic energy (microwave).  By measuring relative permittivity 
(commonly abbreviated to Epsilon relative Er) the dielectric properties of the AK can be determined.   
 
The established method of measurement requires the tissue/material under test to come into contact 
with a specially designed probe attached to an instrument that measures the response to a radiated 
signal at the same frequency (8GHz) as that used in Emblation’s product “Swift”. There are a number of 
instrument and probe manufacturers e.g. Keysight (HP/Agilent), SPEAG, Anritsu. The probe can be 
used to test solids, liquids and biological tissues by placing the probe in direct contact for a few seconds 
whilst remaining still during data acquisition by the instrument. 
 
The instrument (Anritsu MS46122A) providing the probe excitation conforms to the following standards: 
CE Mark, Low voltage (2006/95/EC) and Safety (EN 61010-1:2010). The energy imparted into the 
lesion for the measurement will not exceed 0.5mW, by way of comparison this is far less than a mobile 
phone (up to 500mW) and a FitBit (1.6mW) thus there is no inherent danger to the volunteer.  
 
Emblation employees will operate the instruments and direct the subjects to the probe. Other study 
team staff may work in conjunction with NHS staff at the time of recruitment and/or at the time of 
measurement. 
 
Microwave energy is converted to heat in the skin layers and forms the basis of the therapy. The target 
temperature of 43-46C is crucial in eliciting the correct immune response in the tissue.  As the current 
instrument is ‘tuned’ with an antenna for plantar warts, it may not be as efficient at imparting the energy 
into the AK lesions and the target temperature may not be achieved with the same power and duration 
settings. Conversely, if the AK provides a more efficient conversion of microwave to temperature, 
potentially too high a temperature may be reached at a given power and duration combination.  Stage 1 
data will be analysed to model the efficiency of the current antenna in computer simulations and values 
for input power (W) and duration (s) will be derived from the modelling data, subsequently to be used in 
the stage 2 of the trial. This will provide the correct dose of microwave energy to be used in Stage 2.   
 
Once the settings required for AK have been determined, we will recruit participants into Stage 2 in 
order to determine efficacy, long term resolution, tolerability and potential mode of action of microwave 
treatment for AK. 
 
 
2 
STUDY OBJECTIVES & OUTCOMES  
This is a two-stage feasibility study to determine if focussed microwave energy is a suitable treatment for 
AK. 
 
The two study stages are as follows: 
Stage 1:  
To determine the electrical properties of permittivity in AK on the hand and bald scalp for subsequent 
optimisation of the SWIFT instrument to provide the correct dose of microwave energy to the AK.  
 
Stage 2:  
1. Evaluate the efficacy of microwave energy as a treatment for AK 
2. Evaluate the long-term resolution of AK following microwave treatment 
3. Assess the feasibility and acceptability of using microwave energy as a treatment for AK 
4. Identify the potential mode of action of microwave energy in the treatment of AK 
 
 

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Table 1: Stage Primary Objective and Outcome Measures 
 
Primary Objective: 
Outcome Measure: 
Time point of outcome 
measured 
To determine the permittivity of 
clinically determined thick and thin 
AK on the hand and balding scalp 
using measurement equipment. 
Dielectric permittivity (Er) 
measurement relative to air 
Each AK measured up 
to 6 times on a single 
occasion 
 
 
Table 2: Stage 2 Primary Objectives and Outcome Measures 
 
Primary Objective: 
Outcome Measure: 
Time point of outcome 
measured 
Evaluate the efficacy of microwave 
therapy versus no treatment on the 
resolution of AK lesions using 
visual assessment 
Full or partial resolution of the AK 
assessed by skin examination 
Baseline (day 0) versus 
day 8, day 15, day 28, 
day 42, day 60 and day 
120 
 
 
Table 3: Stage 2 Secondary Objectives and Outcome Measures 
 
Secondary Objective: 
Outcome Measure: 
Time point of outcome 
measured 
To 
evaluate 
the 
long-term 
resolution 
of 
AK 
following 
microwave treatment 
Full or partial resolution of the AK 
assessed by skin examination 
Day 60 and day 120 
To evaluate patient acceptability of 
the use microwave energy as a 
therapy for AK 
Number of Adverse Events per 
participant 
and 
patient 
acceptability 
0, day 8, day 15, day 28, 
day 42, day 60 and day 
120 
Identify the potential mode of 
action of microwave therapy in the 
treatment of AK 
 
Changes in biomarkers of cell 
proliferation, survival and stress 
responses and the expression and 
activity of other genes in the biopsy 
tissue. 
Day 15 OR day 42 
 
 
 
3 
  STUDY DESIGN 
3.1 
STUDY DESCRIPTION 
This study will be delivered in two stages.  Stage one is a single site, one day, volunteer study aiming to 
recruit between 6 and 10 volunteers to identify a minimum of 12 Thick and 12 Thin evaluable AKs.  
Volunteers with diagnosed clinically typical precancerous AK will be recruited from the Department of 
Dermatology or Plastic Surgery, Ninewells Hospital, NHS Tayside.  Once consented to the study, the 
clinician will categorize the AKs on the participants hand and/or visible scalp or forehead as either Thick 
or Thin.  Between 3 and 10 AK will be measured using a low dose of electromagnetic energy for up to 6 
times and the Er data collected.   From this data we will determine the permittivity of the Thick and Thin 
AK, enabling the SWIFT instrument settings to be optimized for the dose of microwave treatment 
confirmed.  This dose will be chosen for the main trial. 
 

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Stage 2: MTAK main trial.   The main trial is a 4-month, single site, randomized, internally controlled trial 
comparing microwave energy therapy versus no treatment, with the participants acting as internal 
controls. Up to 12 evaluable participants with clinically confirmed precancerous AK on the bald scalp or 
forehead or dorsal region of the hand will be recruited from the Departments of Dermatology or Plastic 
Surgery, Ninewells Hospital, NHS Tayside.   
 
Participants will give informed consent after they have received the Participant Information Sheet (PIS) 
and had adequate time to consider whether they wish to participate in the trial.  Participants enrolled in 
the trial will undergo a screening visit (visit 1) to include a check of inclusion and exclusion criteria, 
physical exam and medical history.  The screening and baseline visits may be combined if the 
participant is not currently taking any prescribed treatments for AK.  Participants taking prescribed 
treatments for AK will be asked to stop taking the treatment for 4 weeks.  If clinically feasible, 
nonsteroidal anti-inflammatory (NSAID) medication will also be stopped for 4 weeks prior to receiving 
microwave therapy.  At the baseline visit (visit 2) participants will have the AKs on their hands and/or 
visible scalp recorded on an acetate map and photographed.  AK will be graded depending on their 
thickness as this is used to inform the number of microwave treatments the participant may be given.  
Thin AK will receive one application of microwave treatment while thick AK may receive two.  
Participants will be randomized 1:1 to receiving treatment on either the left or right hand, or left or right 
side of visible scalp.  One of the AKs on the side receiving microwave treatment, will be pre-selected for 
biopsy at a later visit.   
 
Participants will receive microwave energy treatment at the baseline visit.  The microwave instrument, 
SWIFT, manufactured by Emblation and CE marked for dermatology applications, will be used to 
deliver the microwave treatment.  The microwave dose will be between 2 Watt and 4 Watt.  The 
microwave treatment will consist of 3, 2 to 3 second bursts delivered to the same lesion with 5-20 
seconds between bursts.  These doses have previously been shown to be effective and well tolerated 
with no adverse events in clinical studies by Emblation in the treatment of plantar viral warts.  Up to a 
maximum of 10 AK lesions per participant will be treated with microwave energy treatment. Participants 
will be asked about any discomfort experienced at the site of microwave treatment immediately after 
treatment and 30 minutes after treatment. 
 
Participants will be reviewed at visit 3 (day 8) and visit 4 (day 15) and photographs taken of the AKs on 
the hands and/or head. If the AK has clinically responded/resolved following the first dose of microwave 
energy, the biopsy of the predetermined AK will be performed at visit 4 (day 15).   
 
All participants will be contacted by telephone on day 21 (visit 5) to assess any adverse events at the 
site of treatment and biopsy (if relevant). 
 
All participants will be reviewed at visit 6 (day 28) and photographs taken of the AKs on the hands 
and/or head.  Participants may receive a second dose of microwave energy treatment at Visit 6 (day 28) 
based on clinical assessments. Participants will be asked about any discomfort experienced at the site 
of microwave treatment immediately after treatment and 30 minutes after treatment. 
 
All participants will be contacted by telephone on day 35 (visit 7) to assess any adverse events at the 
site of treatment.   
 
Participants will be reviewed at visit 8 (day 42) and photographs taken of AK on hands and/or head.  If 
the participant received a second application of microwave treatment at visit 6, the biopsy of the 
predetermined AK will be performed at this visit (visit 8).   
 
All participants will be contacted by telephone on day 49 (visit 9) to assess any adverse events at the 
site of treatment and biopsy (if relevant). 
 
All participants will be reviewed at visit 10 (day 60) and visit 11 (day 120) with clinical and photographic 
mapping of AK within treatment and contralateral untreated zones on the hands and/or head.  
Participants will be asked about their experience of the microwave therapy, for example, what they liked 
and disliked about it. 
 

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Participants will be asked at each visit (face to face and over the telephone) to provide details of any 
adverse events, in particular at the site of microwave treatment or biopsy, such as if they have 
experienced any stinging, redness, tingling, numbness or soreness.   
 
3.2 
INTERVENTION 
Stage 1:  
Using the instrument described in 1.2, the sensitivity of the measurement requires cable movements to 
be minimised between the hardware and sensor component thus it is envisaged that the patient will 
move and orient themselves such that the tissue area contacts the probe rather than vice-versa. 
Ergonomics will be considered during the measurement set up to ensure no discomfort will be 
experienced during the process. To have robust, statistically valid data each lesion will be measured up 
to 6 times. The total time to achieve a patient measurement set is estimated to be 15 minutes, of which 
the hand or head will need to be stationary for 10s for each acquisition.    
 
Stage 2: 
The microwave treatment will be delivered using the microwave instrument, SWIFT, manufactured by 
Emblation and CE marked for this indication, will be used to deliver the microwave treatment.   A 
measured dose, determined from data acquired from Stage 1 of this study, will be used per AK. The 
microwave dose will be between 2 Watt and 4 Watt.  The microwave treatment will consist of 3, 2 to 3 
second bursts delivered to the same lesion with 5-20 seconds between bursts.  Up to a maximum of 10 
AK lesions per participant will be treated with microwave energy treatment. 
 
3.3 
STUDY FLOWCHART 
See appendix 1 for Stage 1 study flow chart and Appendix 3 for Stage 2 study flow chart. 
 
3.4 
STUDY MATRIX 
See Appendix 2 for Stage 1 study matrix and Appendix 3 Stage 2 study matrix. 
 
3.5 
STUDY ASSESSMENTS 
Study assessments will be performed according to the Appendix 1, Stage 1 Study Matrix and Appendix 
4, Stage 2 Study Matrix.  Where study assessments identify any incidental findings these will be 
communicated to the participants GP, with the participant’s consent. 
 
Stage 1 primary end point will be Dielectric permittivity (Er) measurement relative to air. 
 
Stage 2 primary end point is complete or partial resolution of the AK determined by skin examination.  
Secondary end points will be: 
1) Complete or partial resolution of the AK  after 4 months to determine persistence of AK 
resolution 
2) Number of adverse events recorded per participant and patient acceptability to determine 
participant acceptability of use of microwave therapy for the treatment of AK 
3) Changes in expression and activity of biomarkers of cell proliferation, cell survival and cellular 
stress responses and the expression and activity of other relevant genes and their products in 
the biopsy tissue 
 
 
3.6 
STUDY SAFETY ASSESSMENTS 
3.6.1 
Physical examination 
A physical examination will be performed at screening to exclude participants with co-morbidities or 
other clinical disorders that would constitute an exclusion from the study. 
 
3.6.2 
Hearing Aids 
Participants with AK on the scalp will be asked to remove hearing aids before microwave treatment.  
 

MTAK protocol v5 26-09-2018 
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3.6.3 
Visual examination 
The site of microwave treatment will be assessed at each visit for redness or other inflammation.  
 
3.6.4 
Potential discomfort and skin biopsy procedure 
Some minor discomfort may be experienced during microwave treatment. As microwave energy 
initiates heating, the pain will be similar to something hot touching their skin. In other studies, 
participants found that when therapy was applied for up to 5 seconds, any pain started after 2-3 
seconds.  Pain stopped immediately when treatment stopped as there is no thermal inertia from the 
delivery at the tip-lesion interface. Generally microwave was well tolerated.  In order to minimise pain, 
treatment will only be delivered for 2-3 seconds.  Microwave treatment may lead to a blanching or 
reddening of skin at the treatment site.  This should go away after 24 hours.  Participants will be 
advised to take simple pain relief such as paracetamol should they suffer any discomfort. 
 
Prior to biopsy, participants will be given an injection of local anaesthetic into skin surrounding the AK 
and are likely to feel some momentary discomfort (stinging) before the site becomes numb. Thereafter 
the procedure is painless.  Once the local anaesthetic has worn off, the biopsy site may feel painful for 
24 hours.  Participants will be advised to take paracetamol if needed.  Usually, biopsy sites will be 
closed with a single skin suture that will need to be removed after 2 weeks at the next clinical 
assessment. Biopsy sites may occasionally bleed or become infected.  Participants will have a 
telephone number to ring for advice and an opportunity to return early if there are any concerns. 
 
3.7 
TISSUE 
One AK from the microwave treatment allocation will be pre-selected at the baseline visit for biopsy at 
either visit 4 or visit 7 depending on the treatment regimen adopted by the CI.  Part of the biopsy will be 
sent for routine histopathology.  The remainder of the biopsy sample will be sent to the Tayside Tissue 
Biorepository and expression and activity of relevant genes and their products will be analysed by the 
research team to identify the cellular pathways activated by microwave energy in the skin.  This is a 
mechanistic investigation, not a genetic test.  The research biopsy samples will be retained by Tayside 
Tissue Biorepository for 5 years.  
 
3.8 
INCIDENTAL FINDINGS 
Any incidental findings (IF: previously undiagnosed condition) considered to be clinically significant will 
be reported to the participant’s GP and/or consultant by the CI or Site PI, with the consent of the 
participant. 
 
3.9 
  STUDY POPULATION 
Participants with clinically confirmed precancerous AK on the bald scalp or forehead or dorsal region of 
the hand recruited from the dermatology or plastic surgery outpatient clinics. 
 
 
3.10 NUMBER OF PARTICIPANTS 
Stage 1 
Up to 10 participants with clinically diagnosed AK will be recruited from the Department of Dermatology 
and Plastic Surgery outpatients’ clinics Ninewells Hospital, NHS Tayside.   
 
Stage 2 
Up to 12 participants with clinically diagnosed AK will be recruited from the Department of Dermatology, 
Ninewells Hospital, NHS Tayside.  Participants will be randomized 1:1 to receive treatment on their left 
or right hand or left or right side of the visible scalp. 
 
3.11 INCLUSION CRITERIA 
The same inclusion criteria will be applied to Stage 1 and Stage 2. 
 

MTAK protocol v5 26-09-2018 
13 
 
 
Male or female participants 
 
Age 18 years and over 
 
Clinical diagnosis of precancerous Actinic Keratosis made by a dermatologist 
 
Able to perform study assessments 
 
 
3.12 EXCLUSION CRITERIA 
The same inclusion criteria will be applied to Stage 1 and Stage 2. 
 
Inability to give informed consent 
 
ICD, pacemaker or other implantable device 
 
Metal implants at site of treatment 
 
Known allergy or intolerance to microwave therapy 
 
Unstable co-morbidities (cardiovascular disease, active malignancy, vasculopathy, inflammatory 
arthritis) which, in the opinion of the CI, would make the patient unsuitable to be enrolled in the 
study. 
 
Individuals who are immunosuppressed (organ transplant recipients, haematologic malignancies, 
HIV). 
 
Individuals will not be enrolled to the study if they are participating in the clinical phase of another 
interventional trial or have done so within the last 30 days. Individuals who are participating in 
the follow-up phase of another interventional trial, or who are enrolled in an observational study, 
will be co-enrolled where the CIs of each study agree that it is appropriate. 
 
 
4 
PARTICIPANT SELECTION AND ENROLMENT 
 
4.1 
IDENTIFYING PARTICIPANTS 
Identification of participants is the same for both Stage 1 and Stage 2.  Participants will be identified by 
the CI or members of the clinical care team from the Department of Dermatology, or the Department of 
Plastic Surgery Ninewells Hospital, NHS Tayside.  Clinic lists will be reviewed by the CI or delegate and 
medical records checked to identify suitable patients who will then either be approached and given the 
PIS when they attend clinic or will be posted an invitation letter and the PIS.  If appropriate, Caldicott 
approval for this activity will be sought.  Contact at clinic will be by the CI or delegate.  Postage of the 
invitation letter and PIS will be carried out by the CI or delegate. Participants will be provided with a 
patient information sheet at least 24 hours in advance. Members of the study team will call patients after 
the PIS has been sent out to discuss the study and patients that return the reply slip attached to the PIS 
to arrange the screening visit. 
 
4.2 
CONSENTING PARTICIPANTS 
For Stage 1 and Stage 2, participants will be consented by the CI or other members of the research team.  
Participants will be given at least 24 hours to review the PIS. 
 
When first contact is via letter a PIS will be sent which gives a detailed overview of the study.  Participants 
will be asked to contact the research team if they are interested in the study.  When first contact is in a 
hospital clinic they will be given the PIS and will be asked to contact a member of the research team by 
telephone or email.  Research team contact details will be provided on the PIS. 
 
Individuals interested in taking part will be given at least 24 hours to consider their participation in the 
study before a screening visit is arranged by the CI or delegate, at which participants will be able to ask 
any questions about the study.  If they decide to participate, written informed consent will be obtained 
and eligibility criteria confirmed.   
 

MTAK protocol v5 26-09-2018 
14 
 
Should a participant request to speak with a physician from the study team, the consent process will not 
be completed until the participant has spoken to the physician and had all their questions answered to 
their satisfaction. 
 
For adults who lose capacity their previous wishes will remain legally binding and this will remain valid 
unless the protocol changes significantly. If this occurs and further consent is required from a participant 
who has lost capacity, the appropriate person will be asked for their consent. In all cases the CI or 
delegate will consult with carers and take note of any signs of objection or distress from the participant – 
the participant will be withdrawn if they raise objection. Where deemed appropriate the participant will be 
withdrawn from any further clinical intervention and agreement will be sought from a carer to allow data 
collection. 
 
The original informed consent form will be filed in the trial master file (TMF) and a copy will be given to 
the participant and a copy filed in the participant’s medical notes. 
 
The informed consent process will be conducted in compliance with TASC SOP07: Obtaining Informed 
Consent from Potential Participants in Clinical Research 
4.3 
SCREENING FOR ELIGIBILITY 
No pre- or post-consent screening will be conducted for either stage of the study.  Participants recruited 
to Stage 2, the RCT, will be required to stop using any prescribed treatment for AK for at least 4 weeks 
before starting the trial. 
 
4.4 
INELIGIBLE AND NON-RECRUITED PARTICIPANTS  
The reason(s) for ineligibility will be explained to participants and any questions they have will be 
answered. They will be thanked for their participation in screening and any relevant information from 
this will be added to their hospital notes and be communicated to their GP and consultant where the 
patient consents for this to happen. Patients will be asked if they wish to rescreen if they meet the 
criteria described above. 
 
4.5 
RANDOMISATION  
4.5.1 
Randomisation  
Stage 1 is not randomised.  Randomisation in stage 2 will be performed by TCTU using TRuST, a web 
based, GCP compliant randomization system.  There will not be any stratification or minimisation. 
 
4.5.2 
Intervention Allocation 
The site of treatment, scalp or hand, is a clinical decision made at the time of the baseline visit.  
Randomisation will be to treatment of the left or right hand, or randomisation to treatment of the left or 
right side of the visible scalp.  There will be no stratification or minimisation. 
 
4.5.3 
Withdrawal procedures 
If participants withdraw from microwave treatment, the study team will ask them if they are willing to 
remain in the trial and complete trial assessments.  If a participant withdraws from the trial and does not 
wish to return for trial visits, contact with them will be maintained by the CI or delegate to ensure 
resolution of adverse events.  If withdrawal is due to an AE, it will be recorded on the CRF and AE log. 
 
All participants will be asked about any adverse events at each visit and these will be recorded in the 
trial AE log.  
 
Participants are free to withdraw from the trial at any time.  The reason, if known, will be recorded in the 
CRF and participants medical notes. 

MTAK protocol v5 26-09-2018 
15 
 
 
Although a participant is not obliged to give reason(s) for withdrawing prematurely, if the participant 
appears lost to follow up, the CI will make a reasonable effort to ascertain the reason(s), while fully 
respecting the individual’s rights, and will demonstrate that everything possible was done in an attempt 
to find any participant lost to follow-up. Those lost to follow-up or withdrawn will be identified and a 
descriptive analysis of them provided, including the reasons for their loss and its relationship to 
treatment and outcome.  
 
5 
DATA COLLECTION & MANAGEMENT 
5.1 
DATA COLLECTION 
The CI will maintain source documents for each patient in the study, consisting of case and visit notes 
(hospital or clinic medical records) containing demographic and medical information and the results of 
any other tests or assessments. All information on CRFs must be traceable to these source documents 
in the patient's case notes. 
  
5.2 
DATA MANAGEMENT SYSTEM 
Data management will be conducted in compliance with TASC SOPs on Data Management, TASC 
SOP53 Data Management Systems in Clinical Research. 
 
The data management system (DMS) will be Excel as approved by Sponsor.  
The DMS will be based on the protocol and CRF for the study and individual requirements of the 
investigators. The CRF will collect only information that is required to meet the aims of the study and to 
ensure the eligibility and safety of the participant. The study database will be compliant with TASC SOP53 
Data Management Systems in Clinical Research.  
 
The database is managed in line with all applicable principles of medical confidentiality and UK law on 
data protection, namely, the Data Protection Act 1998, which brought UK law into line with the EU Data 
Protection Directive. The Data Controller will be the University of Dundee and the Data Custodian will be 
the CI. 
The CI may delegate CRF completion but is responsible for completeness, plausibility and consistency 
of the CRF. Any queries will be resolved by the CI or delegated member of the study team.  
Database lock will be conducted in compliance with TASC SOP32 Locking Clinical Study Databases. 
 
 
6 
   STATISTICS AND DATA ANALYSIS 
6.1 
SAMPLE SIZE CALCULATION 
There have been no previous randomised controlled trials of the effects of microwave energy as a 
treatment for AK.  However, it is expected that microwave energy is converted to heat in the skin layers 
and forms the basis of the therapy as seen in the successful treatment of plantar viral warts.  This is a 
pilot study to compare the effect of microwave treatment against no treatment of AKs with participants 
acting as their own internal controls. 
 
It is expected that the number of AKs will be approximately the same number left and right and over the 
12 proposed patients it should equal out even if not exactly matched within an individual patient.   
 
Assuming we recruit 10 participants, the participants will have multiple AK lesions to treat so if we 
assume a minimum of 3 and maximum of 10 AK per patient within the treatment zone, there will be 
between 30 and 100 treated AK and an equivalent number of untreated control AKs; potentially 

MTAK protocol v5 26-09-2018 
16 
 
between 60 and 200 AK.  If we assume that there will be 100 AK (50 treated; 50 mapped and followed 
but not treated) with on average 10 per patient, this will result in approximately 50 lesions in which to 
assess both efficacy and how tolerable the treatment is.  Given 50 treated vs 50 untreated in a paired 
analysis with McNemar’s test then power is 80% to detect a difference in proportion >25% full or partial 
resolution of 0.33. Given the repeated measures of AK over say 6 visits then we will have 300 paired 
measurements. Based even on a smaller mean number of visits of say 3 then the number of pairs is 
increased by the inflation factor (IF) to 55 assuming ICC = 0.05. Hence with a mean of 3 visits ie. 150 
paired measurements power would be 80% to detect a difference of 0.2 between treated and untreated 
in proportion >25% full or partial resolution. 
 
6.2 
PROPOSED ANALYSES 
The unit of analysis will be the individual AK lesion. The comparison will be within subject between left 
and right sides or vice versa. Analysis will follow the guidance of ICH E9 and based on intention-to-
treat. The primary outcome will be full or partial resolution of the AK, which at the lesion level is binary 
and so non-linear models will be utilised. Random effects for subject and visit (up to 6) will be modelled 
with mixed models. The main parameter will represent treated vs. untreated differences. Adjustment will 
also be made for baseline, gender, age, skin site of treatment and AK subtype. 
 
Analyses will be implemented in SAS 9.4 and quality control of programs will follow the relevant TASC 
SOPs.  
6.3 
MISSING DATA 
Mixed models assume data is missing at random (MAR) for visits and all visit data is included and so no 
multiple imputation will be carried out. 
6.4 
TRANSFER OF DATA 
Delegated research staff will enter the data required by the protocol into the CRFs following training in 
the definitions and methods used in completing the CRF. On completion of data collection the 
Investigator must certify that the data entered into the CRFs are complete and accurate.  
 
Data verification and cleaning will be performed as per TASC local procedures.  
 
Post database lock for stage 1 and stage 2, anonymised data will be encrypted and provided to 
Emblation.  All data will be stored on a password protected server with rolling back up in place. 
 
Data preservation and sharing will be in accordance with established procedures at the University of 
Dundee (see http://www.dundee.ac.uk/library/research/datamanagement/). General laboratory data 
methods and results will be documented in laboratory notebooks and then analysed and written up for 
publication for dissemination to the scientific community. All electronic data will be stored on secure 
personal computers and with rolling off-Site backup – the University of Dundee has central provision for 
this process. All data and laboratory notebooks will be retained for at least ten years, in accordance with 
general RCUK guidelines. 
 
 
7 
   STUDY MANAGEMENT AND OVERSIGHT ARRANGEMENTS 
7.1    STUDY MANAGEMENT GROUP 
The study will be co-ordinated by a Trial Management Group (TMG), consisting of the Chief Investigator 
(CI), at least one representative of Emblation, a representative of TCTU representative and a 
representative of the CRC. 
 

MTAK protocol v5 26-09-2018 
17 
 
7.2 
STUDY STEERING COMMITTEE  
The study will not have a separate TSC as the remit will be carried out by the TMG. 
 
7.3 
DATA MONITORING COMMITTEE 
The study will not have a separate DMC as the remit will be carried out by the TMG. 
 
7.4 
INSPECTION OF RECORDS 
The CI, PIs and all institutions involved in the study will permit study related monitoring, audits, and REC 
review. The CI agrees to allow the Sponsor or, representatives of the Sponsor, direct access to all study 
records and source documentation. 
 
 
8 
  GOOD CLINICAL PRACTICE 
8.1 
ETHICAL CONDUCT OF THE STUDY 
The study will be conducted in accordance with the principles of good clinical practice (GCP). 
In addition to Sponsorship approval, a favorable ethical opinion will be obtained from the appropriate REC 
and appropriate NHST R&D approval will be obtained prior to commencement of the study. 
 
8.2 
CONFIDENTIALITY 
All laboratory specimens, evaluation forms, reports, and other records will be identified in a manner 
designed to maintain participant confidentiality. All records will be kept in a secure storage area with 
limited access to study staff only. Clinical information will not be released without the written permission 
of the participant, except as necessary for monitoring and auditing by the Sponsor or its designee. The 
CI and study staff involved with this study will not disclose or use for any purpose other than performance 
of the study, any data, record, or other unpublished, confidential information disclosed to those individuals 
for the purpose of the study. Prior written agreement from the Sponsor or its designee will be obtained 
for the disclosure of any said confidential information to other parties. 
 
8.3 
DATA PROTECTION 
The CI and study staff involved with this study will comply with the requirements of the Data Protection 
Act 1998 with regard to the collection, storage, processing and disclosure of personal information and will 
uphold the Act’s core principles. The CI and study staff will also adhere, if appropriate, to the current 
version of the NHS Scotland Code of Practice on Protecting Patient Confidentiality.  Access to collated 
participant data will be restricted to the CI and appropriate study staff. 
Computers used to collate the data will have limited access measures via user names and passwords. 
Published results will not contain any personal data that could allow identification of individual 
participants. 
 
8.4 
INSURANCE AND INDEMNITY 
 
The University of Dundee and Tayside Health Board are Co-Sponsoring the study. 
 
Insurance – The University of Dundee will obtain and hold a policy of Public Liability Insurance for legal 
liabilities arising from the study. 
 

MTAK protocol v5 26-09-2018 
18 
 
Tayside Health Board will maintain its membership of the Clinical Negligence and Other Risks Insurance 
Scheme (“CNORIS”) which covers the legal liability of Tayside in relation to the study. 
 
Where the study involves University of Dundee staff undertaking clinical research on NHS patients, such 
staff will hold honorary contracts with Tayside Health Board which means they will have cover under 
Tayside’s membership of the CNORIS scheme. 
 
Indemnity The Co-Sponsors do not provide study participants with indemnity in relation to participation 
in the Study but have insurance for legal liability as described above. 
 
 
9 
    ADVERSE EVENTS 
9.1 
DEFINITIONS 
 
Adverse Event (AE) 
Any untoward medical occurrence in a clinical research  participant 
which does not necessarily have a causal relationship with study 
participation 
Serious Adverse Event 
(SAE) 
A serious adverse event is any untoward medical occurrence that: 
 
results in death 
 
is life threatening  
 
requires hospitalisation or prolongation of existing 
hospitalisation 
 
results in persistent or significant disability or incapacity 
 
is a congenital anomaly or birth defect 
 
Or is otherwise considered serious 
 
9.2 
RECORDING AND REPORTING AE 
All AEs will be recorded on the AE Log in the CRF and will be assessed for severity by the CI or delegate. 
AEs will be recorded from the time a participant gives consent to join the study until the participant’s last 
study visit.  
The CI will make a clinical judgment as to whether or not an AE is of sufficient severity to require the 
participant’s removal from the study.  A participant may also voluntarily withdraw from treatment due to 
what he or she perceives as an intolerable AE.  If either of these occurs, the participant should, if required, 
be offered an end of study assessment and be given appropriate care under medical supervision until 
symptoms cease, or the condition becomes stable.  SAEs will be followed up until 30 days after 
participant’s last visit. 
 
The CI or delegate will ask about the occurrence of AEs and hospitalisations at every visit during the 
study. SAEs which are both unexpected and related to study participation will be submitted on an 
HRA NCTIMP Safety Report form to the REC by the CI, within 15 days of becoming aware of the SAE, 
and copied to the Sponsor Research Governance Office. 
Worsening of the condition under study will not be classed as an AE, but will be defined as an outcome. 
Pre-specified outcome(s) will not be classed as an AE but as an outcome. Elective admissions and 
hospitalisations for treatment planned prior to randomisation, where appropriate, will not be considered 
as an AE. However, SAEs occurring during such hospitalisations will be recorded. 
 

MTAK protocol v5 26-09-2018 
19 
 
10 ANNUAL REPORTING REQUIREMENTS 
Annual reporting will be conducted in compliance with TASC SOP 15: Preparing and Submitting Progress 
and Safety Reports in CTIMPs and Non-CTIMPs, as a condition of sponsorship and as a condition of a 
favourable opinion from a REC. An HRA Annual Progress Report for NCTIMPs will be prepared and 
submitted by the CI to REC, and copied to the Sponsor, on the anniversary date of the REC favourable 
opinion. 
 
Any safety reports additional to SAE reports, for example, reports of a DMC, will be sent by the CI to 
REC, with a Safety Report Form, and to the Sponsor.  
 
 
11    STUDY CONDUCT RESPONSIBILITIES 
11.1 PROTOCOL AMENDMENTS, DEVIATIONS AND BREACHES 
The CI will seek approval for any amendments to the Protocol or other study documents from the Sponsor, 
REC and NHST R&D Office. Amendments to the protocol or other study docs will not be implemented 
without these approvals.  
In the event that a CI needs to deviate from the protocol, the nature of and reasons for the deviation will 
be recorded in the CRF, documented and submitted to the Sponsor. If this necessitates a subsequent 
protocol amendment, this will be submitted to the Sponsor for approval and then to the appropriate REC 
and lead NHS R&D Office for review and approval.  
In the event that a serious breach of GCP or protocol is suspected, this will be reported to the Sponsor 
Governance Office immediately 
 
11.2 STUDY RECORD RETENTION 
Archiving of study documents will be for 5 years after the end of study. 
 
11.3 END OF STUDY 
The end of study is defined as database lock. The Sponsor, CI have the right at any time to terminate the 
study for clinical or administrative reasons.  
The end of the study will be reported to the Sponsor and REC within 90 days, or 15 days if the study is 
terminated prematurely. The CI will ensure that any appropriate follow up is arranged for all participants. 
A summary report of the study will be provided to the Sponsor and REC within 1 year of the end of the 
study. 
 
12   REPORTING, PUBLICATIONS AND NOTIFICATION OF RESULTS 
12.1 AUTHORSHIP POLICY 
Ownership of the data arising from this study resides with the study team and their respective employers. 
On completion of the study, the study data will be analysed and tabulated, and a clinical study report will 
be prepared.  
 
12.2 PUBLICATION 
The clinical study report will be used for publication and presentation at scientific meetings. Investigators 
have the right to publish orally or in writing the results of the study.  Publications will be reviewed according 
to the agreed contractual terms of the grant funding but will not restrict the general rights outlined above 
for Investigators to publish the results of the study. 
Summaries of results will also be made available to Investigators for dissemination within their clinical 
areas (where appropriate and according to their discretion). 
 

MTAK protocol v5 26-09-2018 
20 
 
12.3 PEER REVIEW 
This project has been peer reviewed by the funder, Innovate UK, an executive non-departmental public 
body, sponsored by the Department for Business, Energy and Industrial Strategy.  The protocol has 
been peer reviewed by the Sponsor and by Emblation, the industrial partner on the grant award. 
  
 
13 REFERENCES 
 
Bristow I, Lim WC, Lee A, Holbrook D, Thomson P, Webb C, Polak M, Ardern-Jones MR.  Microwave 
therapy for cutaneous human papillomavirus infection.  Eur J Dermatol 2017; 27(5): 511-8 
Criscione BD, Weinstock MA, Naylor MF, et al.  Actinic keratoses: Natural history and risk of malignant 
transformation in the Veterans Affairs Topical Tretinoin Chemoprevention Trial. Cancer 2009; 115: 
2523-30. 
Eder J, Prillinger K, Korn A, et al.  Prevalence of actinic keratosis among dermatology outpatients in 
Austria.  Br J Dermatol 2014; 171: 1415-21 
Goon PK, Greenberg DC, Igali L, Levell NJ. Squamous Cell Carcinoma of the Skin has More Than 
Doubled Over the Last Decade in the UK. Acta Derm Venereol. 2016; 96(6):820-1.  
Liang P, Wang Y, Microwave Ablation of Hepatocellular Carcinoma. Oncology 2007;72(suppl 1):124-
131 
 
Marks R, Rennie G, Selwood TS. Malignant transformation of solar keratoses to squamous cell 
carcinoma. Lancet 1988; 8589: 795-7 
Martin R.C.G. (2011) Microwave Ablation and Hepatocellular Carcinoma. In: McMasters K. (eds) 
Hepatocellular Carcinoma:. Springer, New York, NY 
 
Poggi G, Tosoratti N, Montagna B, Picchi C. Microwave ablation of hepatocellular carcinoma. World 
Journal of Hepatology. 2015;7(25):2578-2589. 
  
Wang T, Lu XJ, Chi JC, Ding M, Zhang Y, Tang XY, Li P, Zhang L, Zhang XY, Zhai B. Microwave 
ablation of hepatocellular carcinoma as first-line treatment: long term outcomes and prognostic factors 
in 221 patients. Sci Rep. 2016 Sep 13;6:32728.  
 
 

MTAK protocol v5 26-09-2018 
21 
 
APPENDIX 1: STAGE 1 STUDY FLOWCHART  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Identify participants at dermatology 
and plastic surgery clinics 
 
Participants sent PIS 
Visit 1 Day 1 (n=10) 
 Informed consent 
 Inclusion/exclusion criteria 
 Vital assessments 
 AKs mapped and photographed 
(n=60) 
 Permittivity recorded 
 

MTAK protocol v5 26-09-2018 
22 
 
APPENDIX 2: STAGE 1 STUDY MATRIX 
 
 
 
Type of Visit 
Baseline 
Timeline 
Day 0 
Informed consent 
X 
Inclusion/Exclusion 
X 
Medical History 
X 
Con meds 
X 
Physical Exam 
X 
Permittivity Assessment 
X 
Record AEs 
X 
 
 
 
 
 
 

MTAK protocol v5 26-09-2018 
23 
 
APPENDIX 3: STAGE 2 STUDY FLOW CHART 
 
 
Visit 1 (day -35)
 
Consent/Enrol
 
Identify regions on hand and/or scalp
 
Pretreatment AKs mapped and photographed
 
Stop current AK treatment
EXCLUSION CRITERIA
 
Inability to give informed consent
 
ICD, pacemaker or other implantable 
electric device
 
Metal implants at site of treatment
 
Known allergy or intolerance of 
microwave therapy
 
Unable co-morbidities (acute 
inflammation, cardiovascular disease, 
active malignancy) which would make 
the patient unable to be enrolled in 
the study
 
Participating in a drug trial
All the patients are likely 
to have thin AK lesions 
and few may have a 
mixture of thin and thick 
AK lesions. 
 
Visit 2 (Day 0)
 
Categorise as Thin AK or Thick AK based on the clinical scoring 
(Thin AK= 1 or 2; Thick AK = 3)
 
Randomise to left and right hand side
 
Assign biopsy AK lesion
 
Apply microwave treatment based on the treatment strategy:
          - 3 bursts of 2-3 seconds at 2-4 5 Watt per AK, with 5-20          
seconds between bursts
Visit 3 (Day 8)
 
Photographs of the treated AK lesions
 
Assessment and review
If the patient is currently not 
taking any prescribed drugs for 
AK, then the screening visit (visit 
1) and baseline visit (visit 2) may 
be combined into a single visit
Visit 4 (Day 15)
 
Photographs of the treated AK lesions
 
Assessment and review
Does the AK 
lesion require second 
treatment? 
 
Biopsy of the preselected AK lesion (only 
one lesion per patient)
 
Wait for visit 6
Visit 5 (Day 21) Telephone Visit
 
Collect Con Meds and AEs
 
Photographs of the treated AK lesions
 
Assessment and review
 
Photographs of the treated AK Lesions
 
Assessment and review
 
Apply microwave treatment:
- 3 bursts of 2-3 seconds at 2-4 5 Watt per 
AK, with 5-20 seconds between bursts
 
Photographs of the treated AK lesions
 
Assessment and review
 
Photographs of the treated AK lesions
 
Assessment and review
 
Biopsy of the preselected AK lesion 
(only one lesion per patient) 
Visit 10 (Day 60)
 
Photographs of the treated AK lesions
 
Assessment and review
 
Patient acceptability
Visit 11 (Day 120)
 
Photographs of the treated AK lesions
 
Assessment and review
 
Patient acceptability
End of the study
Identify participants at the clinic
 Assess for eligibility
Yes
Yes
Yes
No
No
No
Visit 7 (Day 35) Telephone Visit
 
Collect Con Meds and AEs
Visit 6
Does the AK 
lesion require second 
treatment? 
Visit 8 (Day 42)
Was the AK lesion 
treated on 
Visit 6? 
Visit 9 (Day 49) Telephone Visit
 
Collect Con Meds and AEs

MTAK protocol v5 26-09-2018 
24 
 
 
APPENDIX 4: STAGE 2 STUDY MATRIX 
 
Visit 11 
Visit 21 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit 9 
Visit 10 
Visit 11 
Type of Visit 
 
Screening 
 
Baseline 
 
 
 
 
 
 
 
 
 
Timeline 
-35 days 
Day 0 
(+/-3 
days) 
Day 8 
(+/-3 
days) 
Day 15 
(+/-3 
days) 
Day 21 
(+/-3 
days) 
Day 28 
(+/-3 
days) 
Day 35 
(+/-3 
days) 
Day 42 
(+/-3 
days) 
Day 49 
(+/-7 
days) 
Day 60 
(+/-7 
days) 
Day 120 
(+/-7 
days) 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
X 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
Con Meds 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical Examination 
X 
X 
X 
X 
 
X 
 
X 
 
X 
X 
Stop current AK treatment 
X 
 
 
 
 
 
 
 
 
 
 
Map AK  
X 
X 
X 
X 
 
X 
 
X 
 
X 
X 
Photograph AKs  
X 
X 
X 
X 
 
X 
 
X 
 
X 
X 
Categorise type of AK as 
Thin or Thick 
 
X 
 
 
 
 
 
 
 
 
 
Randomisation  
 
X 
 
 
 
 
 
 
 
 
 
Pre select AK for biopsy 
 
X 
 
 
 
 
 
 
 
 
 
Microwave treatment of up 
to 10 AKs per participant 
 
X 
 
 
 
X2 
 
 
 
 
 
Visual assessment of 
treated AKs 
 
X 
X 
X 
 
X 
 
X 
 
X 
X 
Biopsy 
 
 
 
X3 
 
 
 
X3 
 
 
 
Patient Acceptability 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Record Adverse Events 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Notes 
1: Screening visits and baseline visit may be combined if participant is not on currently prescribed treatment for AK 
2: Second treatment is based on clinical opinion of CI or delegate 
3: Biopsy performed once during the study.  This will be performed at visit 4 if no second microwave treatment.  If second treatment given, biopsy taken at 
visit 8, not visit 4.