Trial Outcomes & Findings for Microwave Therapy for Treatment of Precancerous Actinic Keratoses (NCT NCT03483935)

Last Updated: 2023-03-06

Results Overview

The resolution of each treated AK lesion will be determined by clinical assessment. Resolution is predetermined as either partial (resolution of the area covered by the microwave probe, but with a rim or persistent AK) or full (complete resolution of the entire AK) over all time periods. Response will be assessed at visits 3 (day 8), 4 (day 15), 6 (day 28), 8 (day 42), 10 (day 60) and 11 (day 120). Mixed-effects logistic regression models analysed the effect of microwave therapy with random effects for participant and visit (≤ 6 per participant). Each visit will be analysed as a categorical variable as they were spaced unequally in time. Variables representing sex, age, skin site (hand/scalp) and AK subtype (thick/thin) will be included as covariates. The data reported in the outcome table is the number of resolved AK lesions.

Recruitment status

COMPLETED

Study phase

Target enrollment

18 participants

Primary outcome timeframe

Baseline, day 8, 15, 28, 42, 60 and 120

Results posted on

2023-03-06

Participant Flow

Participants were recruited to the Stage 1, dose finding study in March 2018. Participants were recruited to Stage 2, the RCT, between May 2018 and October 2018. Participants for both stages were recruited from the Department of Dermatology, Ninewells Hospital, NHS Tayside, UK.

Unit of analysis: Number of AK Lesions

Participant milestones

Participant milestones
Measure	Trial Population Stage 1: Determine the electrical properties of AKs Stage 2: Evaluate the efficacy of microwave energy as a treatment for AK
Stage 1: Dose Setting Study STARTED	7 34
Stage 1: Dose Setting Study COMPLETED	7 34
Stage 1: Dose Setting Study NOT COMPLETED	0 0
Stage 2: Randomised Controlled Trial STARTED	11 179
Stage 2: Randomised Controlled Trial AKs Treated	11 93
Stage 2: Randomised Controlled Trial AKs Not Treated	11 86
Stage 2: Randomised Controlled Trial COMPLETED	11 179
Stage 2: Randomised Controlled Trial NOT COMPLETED	0 0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Finding Population n=7 Participants Consented participants had the electric properties of permittivity in AK on hand and bald scalp assessed for subsequent optimisation of the dose of microwave therapy to be used in the RCT.	RCT Study Population n=11 Participants This was a randomized, internally controlled, feasibility study. Consented participants had the treatment site (scalp/forehead or hands) selected based on a clinical decision. Participants were randomized to treatment to the left or right side. The microwave treatment was delivered using the microwave instrument, SWIFT, manufactured by Emblation and CE marked for this indication. The microwave dose was between 2 Watt and 4 Watt. The treatment will consist of 3, 2 to 3 second bursts delivered to the same lesion with 5-20 seconds between bursts. No treatment was administered to the control side.	Total n=18 Participants Total of all reporting groups
Age, Continuous	74 years STANDARD_DEVIATION 7 • n=7 Participants	78 years STANDARD_DEVIATION 6 • n=11 Participants	NA years STANDARD_DEVIATION NA • n=18 Participants
Sex: Female, Male Female	2 Participants n=7 Participants	4 Participants n=11 Participants	6 Participants n=18 Participants
Sex: Female, Male Male	5 Participants n=7 Participants	7 Participants n=11 Participants	12 Participants n=18 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
History of skin cancer	0 Participants Data were not collected	10 Participants n=11 Participants • Data were not collected	10 Participants n=11 Participants • Data were not collected
History of other cancer	0 Participants Data were not collected	0 Participants n=11 Participants • Data were not collected	0 Participants n=11 Participants • Data were not collected

PRIMARY outcome

Timeframe: Baseline, day 8, 15, 28, 42, 60 and 120

Population: Eleven participants were randomized and 179 AKs (93 treated, 86 untreated) assessed. All participants completed treatment as planned.

Outcome measures

Outcome measures
Measure	Microwave Energy Treatment n=93 AK lesions Microwave dose for participants 1 and 2 was 5 Watt. Dose for participants 3 through 9 was between 2 Watt and 4 Watt. Treatment consists of 3, 2 to 3 second bursts of microwave energy, delivered to the same lesion with 5-20 seconds between bursts.	Control n=86 AK lesions No treatment
Resolution of AK Lesions Following Microwave Treatment Day 8	73 AK lesions	2 AK lesions
Resolution of AK Lesions Following Microwave Treatment Day 15	73 AK lesions	7 AK lesions
Resolution of AK Lesions Following Microwave Treatment Day 28	86 AK lesions	9 AK lesions
Resolution of AK Lesions Following Microwave Treatment Day 42	86 AK lesions	9 AK lesions
Resolution of AK Lesions Following Microwave Treatment Day 60	81 AK lesions	11 AK lesions
Resolution of AK Lesions Following Microwave Treatment Day 120	84 AK lesions	13 AK lesions

PRIMARY outcome

Timeframe: Baseline, day 8, 15, 28, 42, 60 and 120

Population: Eleven participants were randomized and 179 AKs (93 treated, 86 untreated) assessed. All participants completed treatment as planned.

The resolution of each treated AK lesion will be determined by clinical assessment. Resolution is predetermined as either partial (resolution of the area covered by the microwave probe, but with a rim or persistent AK) or full (complete resolution of the entire AK) over all time periods. Treatment will be given at day 1, with a second treatment on day 28 based on a clinical decision. Response will be assessed at visits 3 (day 8), 4 (day 15), 6 (day 28), 8 (day 42), 10 (day 60) and 11 (day 120). Clinical photos will be taken at each hospital visit. Mixed-effects logistic regression models analysed the effect of microwave therapy with random effects for participant and visit (≤ 6 per participant). Each visit will be analysed as a categorical variable as they were spaced unequally in time. Variables representing sex, age, skin site (hand/scalp) and AK subtype (thick/thin) will be included as covariates.

Outcome measures

Outcome measures
Measure	Microwave Energy Treatment n=93 Number of lesions Microwave dose for participants 1 and 2 was 5 Watt. Dose for participants 3 through 9 was between 2 Watt and 4 Watt. Treatment consists of 3, 2 to 3 second bursts of microwave energy, delivered to the same lesion with 5-20 seconds between bursts.	Control n=86 Number of lesions No treatment
Complete Resolution of AKs Following Microwave Treatment Day 8	4 Number of lesions	1 Number of lesions
Complete Resolution of AKs Following Microwave Treatment Day 15	7 Number of lesions	1 Number of lesions
Complete Resolution of AKs Following Microwave Treatment Day 28	20 Number of lesions	2 Number of lesions
Complete Resolution of AKs Following Microwave Treatment Day 42	23 Number of lesions	3 Number of lesions
Complete Resolution of AKs Following Microwave Treatment Day 60	41 Number of lesions	5 Number of lesions
Complete Resolution of AKs Following Microwave Treatment Day 120	39 Number of lesions	6 Number of lesions

PRIMARY outcome

Timeframe: Baseline, day 8, 15, 28, 42, 60 and 120

Population: Eleven participants were randomized and 179 AKs (93 treated, 86 untreated) assessed. All participants completed treatment as planned.

The resolution of each treated AK lesion will be determined by clinical assessment. Resolution is predetermined as either partial (resolution of the area covered by the microwave probe, but with a rim or persistent AK) or full (complete resolution of the entire AK) over all time periods. Treatment will be given at day 1, with a second treatment on day 28 based on a clinical decision. Response will be assessed at visits 3 (day 8), 4 (day 15), 6 (day 28), 8 (day 42), 10 (day 60) and 11 (day 120). Clinical photos will be taken at each hospital visit. Mixed-effects logistic regression models analysed the effect of microwave therapy with random effects for participant and visit (≤ 6 per participant). Each visit will be analysed as a categorical variable as they were spaced unequally in time. Variables representing sex, age, skin site (hand/scalp) and AK subtype (thick/thin) will be included as covariates.

Outcome measures

Outcome measures
Measure	Microwave Energy Treatment n=93 Number of Lesions Microwave dose for participants 1 and 2 was 5 Watt. Dose for participants 3 through 9 was between 2 Watt and 4 Watt. Treatment consists of 3, 2 to 3 second bursts of microwave energy, delivered to the same lesion with 5-20 seconds between bursts.	Control n=86 Number of Lesions No treatment
Partial Resolution of AKs Following Microwave Treatment Day 8	69 Number of Lesions	1 Number of Lesions
Partial Resolution of AKs Following Microwave Treatment Day 15	66 Number of Lesions	6 Number of Lesions
Partial Resolution of AKs Following Microwave Treatment Day 28	66 Number of Lesions	7 Number of Lesions
Partial Resolution of AKs Following Microwave Treatment Day 42	63 Number of Lesions	6 Number of Lesions
Partial Resolution of AKs Following Microwave Treatment Day 60	40 Number of Lesions	6 Number of Lesions
Partial Resolution of AKs Following Microwave Treatment Day 120	45 Number of Lesions	7 Number of Lesions

SECONDARY outcome

Timeframe: Treatment 1 (day 1) and treatment 2 (day 28)

Population: 11 participants had a total of 93 AKs treated at visit 1 (day 1), with 10 participants having a total of 51 of the original 93 AKs receiving a second treatment at visit 6 (day 28).

To evaluate the safety and tolerability of microwave treatment as a therapy for AK, participants were asked about level of pain during treatment. Participants were asked to rate their pain level during each treatment as i) mild, ii) moderate or iii) severe.

Outcome measures

Outcome measures
Measure	Microwave Energy Treatment n=93 Number of AK lesions treated Microwave dose for participants 1 and 2 was 5 Watt. Dose for participants 3 through 9 was between 2 Watt and 4 Watt. Treatment consists of 3, 2 to 3 second bursts of microwave energy, delivered to the same lesion with 5-20 seconds between bursts.	Control n=51 Number of AK lesions treated No treatment
Level of Pain Experienced During Treatment Mild pain during treatment	7 Number of AK lesions treated	5 Number of AK lesions treated
Level of Pain Experienced During Treatment Moderate pain during treatment	32 Number of AK lesions treated	27 Number of AK lesions treated
Level of Pain Experienced During Treatment Severe pain during treatment	54 Number of AK lesions treated	19 Number of AK lesions treated

SECONDARY outcome

Timeframe: Treatment 1 (day 1) and Treatment 2 (day 28)

Population: 11 participants had a total of 93 AKs treated at visit 1 (day 1), with 10 participants having a total of 51 of the original 93 AKs receiving a second treatment at visit 6 (day 28).

To evaluate the safety and tolerability of microwave treatment as a therapy for AK, participants were asked about the duration of pain immediately after each treatment. Duration was grouped into 5 pre-determined periods, i) few seconds, ii) up to 5 minutes, iii) up to 10 minutes, iv) up to 20 minutes and v) over 30 minutes. The decision to administer a second treatment was made by the investigator.

Outcome measures

Outcome measures
Measure	Microwave Energy Treatment n=11 Participants Microwave dose for participants 1 and 2 was 5 Watt. Dose for participants 3 through 9 was between 2 Watt and 4 Watt. Treatment consists of 3, 2 to 3 second bursts of microwave energy, delivered to the same lesion with 5-20 seconds between bursts.	Control n=10 Participants No treatment
Duration of Pain Post Treatment Duration: Few seconds	7 Participants	8 Participants
Duration of Pain Post Treatment Duration: Up to 5 minutes	2 Participants	2 Participants
Duration of Pain Post Treatment Duration: Up to 10 minutes	1 Participants	0 Participants
Duration of Pain Post Treatment Duration: Up to 20 minutes	1 Participants	0 Participants
Duration of Pain Post Treatment Duration: Over 30 minutes	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 15

Population: One AK lesion from the microwave treatment allocation was pre-selected for biopsy. Biopsy taken from all participants 15 days post microwave energy treatment.

To identify the mode of action of microwave treatment on biomarkers of cell proliferation as a therapy for AK. Results are provided on the staining positivity scale of +, ++ and +++. The minimum value is + , meaning the least staining. The maximum value is +++, meaning the most staining identified.

Outcome measures

Outcome measures
Measure	Microwave Energy Treatment n=11 Participants Microwave dose for participants 1 and 2 was 5 Watt. Dose for participants 3 through 9 was between 2 Watt and 4 Watt. Treatment consists of 3, 2 to 3 second bursts of microwave energy, delivered to the same lesion with 5-20 seconds between bursts.	Control No treatment
Change in Ki67 Staining Determined Immunohistochemically by the Use of Specific Antibodies on Fixed Material + stain positivity	9 Participants	—
Change in Ki67 Staining Determined Immunohistochemically by the Use of Specific Antibodies on Fixed Material ++ stain positivity	1 Participants	—
Change in Ki67 Staining Determined Immunohistochemically by the Use of Specific Antibodies on Fixed Material +++ stain positivity	1 Participants	—

SECONDARY outcome

Timeframe: Day 15 OR day 42

Population: all participants treated with microwave therapy.

To identify the mode of action of microwave treatment on biomarkers of cell survival.

Outcome measures

Outcome measures
Measure	Microwave Energy Treatment n=11 Participants Microwave dose for participants 1 and 2 was 5 Watt. Dose for participants 3 through 9 was between 2 Watt and 4 Watt. Treatment consists of 3, 2 to 3 second bursts of microwave energy, delivered to the same lesion with 5-20 seconds between bursts.	Control No treatment
Change in Hematoxylin and Eosin Stain	11 Participants	—

Adverse Events

Stage 1 Dose Finding Study

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Stage 2 RCT

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Stage 1 Dose Finding Study n=7 participants at risk To determine the electrical properties of permitivity in AK on the hand and scalp.	Stage 2 RCT n=11 participants at risk The microwave treatment delivered using the microwave instrument, SWIFT, manufactured by Emblation and CE marked for this indication. The microwave dose was between 5 Watt for the first two participants and 2 Watt and 4 Watt for the remaining nine participants. The treatment will consist of 3, 2 to 3 second bursts delivered to the same lesion with 5-20 seconds between bursts.
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/7 • Adverse event data was collected from the date of consent until the participant's last study visit. For Stage 1, study duration was 1 day. For stage 2, RCT, maximum participant duration on the trial was 35 days washout period (if required) and 120 days trial duration. SAEs were followed up for both stages until 30 days after the participant's last visit. Participants were asked at every visit about the occurrence of adverse events at the site of treatment and biopsy and details of hospitalization. Expected adverse events following microwave therapy include stinging, redness, tingling, numbness or soreness. Participants were asked to score their pain immediately following microwave treatment and 30 minutes after treatment.	9.1% 1/11 • Number of events 1 • Adverse event data was collected from the date of consent until the participant's last study visit. For Stage 1, study duration was 1 day. For stage 2, RCT, maximum participant duration on the trial was 35 days washout period (if required) and 120 days trial duration. SAEs were followed up for both stages until 30 days after the participant's last visit. Participants were asked at every visit about the occurrence of adverse events at the site of treatment and biopsy and details of hospitalization. Expected adverse events following microwave therapy include stinging, redness, tingling, numbness or soreness. Participants were asked to score their pain immediately following microwave treatment and 30 minutes after treatment.

Other adverse events

Additional Information

Prof Charlotte Proby

University of Dundee

Phone: +44 1382 383289

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place