Clinical Trial Results:
Investigations of local skin reactions and safety after combined treatment of basal cell carcinoma using ablative fractional laser and ingenol mebutate - an exloratory, prospective, open-label phase 2a trial.
Summary
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EudraCT number |
2017-002843-14 |
Trial protocol |
DK |
Global end of trial date |
18 May 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Mar 2020
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First version publication date |
08 Mar 2020
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Other versions |
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Summary report(s) |
Abstract |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
0407
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Bispebjerg Hospital
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Sponsor organisation address |
Bispebjerg Bakke23, Copenhagen, Denmark, 2400
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Public contact |
Dermatologisk Afdeling, Bispebjerg hospital, mhaedersdal@dadlnet.dk
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Scientific contact |
Dermatologisk Afdeling, Bispebjerg hospital, 45 22860181, mhaedersdal@dadlnet.dk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
31 Jul 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
18 May 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
18 May 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
1) to investigate local skin reactions and safety of ablative fractional laser (AFXL)-assisted ingenol mebutate treatment of basal cell carcinoma (BCC)
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Protection of trial subjects |
local anaesthesia was performed in the treatment area prior to laser exposure.
A manually customized well (Duoderm!, Denmark)
demarcated the treatment area to avoid IM-induced LSRs of
surrounding healthy skin.
Patients were advised to take paracetamol if they experienced pain after the procedure.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
02 Oct 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Denmark: 20
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Worldwide total number of subjects |
20
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EEA total number of subjects |
20
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
11
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From 65 to 84 years |
8
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85 years and over |
1
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Recruitment
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Recruitment details |
Patients were recruited from the Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark and private dermatological practices in Copenhagen, Denmark. | ||||||
Pre-assignment
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Screening details |
Patients were screened if they seemed to meet inclusion criteria. | ||||||
Pre-assignment period milestones
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Number of subjects started |
20 | ||||||
Number of subjects completed |
20 | ||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
Arms
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Arm title
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One arm | ||||||
Arm description |
- | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Ingenol mebutate
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Investigational medicinal product code |
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Other name |
Picato
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Pharmaceutical forms |
Gel
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Routes of administration |
Cutaneous use
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Dosage and administration details |
Immediately after Ablative Fractional Laser exposure, ingenol meditate
was applied to treatment areas in a thick layer in concentrations
of 0.015% to scalp and facial areas or 0.05% to nonscalp-
non-facial areas. The treatment area was occluded
8 (Tegaderm!, Denmark) for two (0.05%) or 3 days (0.015%).
A second treatment was performed at day 29 if residual BCC
persisted clinically, as evaluated by OCT or RCM.
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
Patients with Fitzpatrick skin type I-III were eligible for the trial if they were a minimum of 18 years old with low-risk, histologically verified superficial or nodular BCC. Low-risk tumours were defined as primary BCCs located outside of the high-risk zone,5 tumours ≤20 mm in face or scalp areas and ≤50 mm in non-face or non-scalp areas. BCCs in the high-risk zone, patients with Gorlin’s syndrome and immunosuppressed patients were excluded from the study | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Tumor clearance
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
At day 90, overall histological clearance rate was 14 of 20
(70%; Table 2). Clearance rates were similar for superficial and
nodular BCCs (P = 0.354) and for BCCs treated with 0.015%
IM concentration vs. 0.05% concentration (P = 0.141). Clinical
clearance rate was 13 of 20 (65%) and further six BCCs appeared
clinically reduced. OCT and RCM cure rate was 12 of 20 (60%).
Overall agreement between evaluation techniques was substantial
(kappa = 0.796, P = 0.0001). Similarly, inter-observer agreement
between evaluations of unblinded and blinded evaluators
was consistent (kappa > 0.8, P < 0.0001).
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End points reporting groups
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Reporting group title |
One arm
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Reporting group description |
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Subject analysis set title |
Tumor clearance
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
At day 90, overall histological clearance rate was 14 of 20
(70%; Table 2). Clearance rates were similar for superficial and
nodular BCCs (P = 0.354) and for BCCs treated with 0.015%
IM concentration vs. 0.05% concentration (P = 0.141). Clinical
clearance rate was 13 of 20 (65%) and further six BCCs appeared
clinically reduced. OCT and RCM cure rate was 12 of 20 (60%).
Overall agreement between evaluation techniques was substantial
(kappa = 0.796, P = 0.0001). Similarly, inter-observer agreement
between evaluations of unblinded and blinded evaluators
was consistent (kappa > 0.8, P < 0.0001).
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End point title |
Tumor clearance [1] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
3 months follow up
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The study was designed as an exploratory study with no formal statistical sample size calculation. Twenty BCCs of superficial or nodular subtype in twenty subjects were considered sufficient to investigate benefit and risk of the treatment. Non-parametric statistics were used for LSR and cosmesis scores, and changes in blood flow measurements. Descriptive data were presented with medians and interquartile ranges (IQR). Wilcoxon matchedpairs test was used to test differences between test a |
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Notes [2] - Out of 20 patients, 14 BCCs cleared after treatment |
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No statistical analyses for this end point |
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Adverse events information [1]
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Timeframe for reporting adverse events |
Adverse events were reported during the study period from patients
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Adverse event reporting additional description |
AEs were mostly moderate siterelated
pain and mild pruritus. Clinical scarring in terms of skin
structural and pigmentation changes was observed in majority of
cleared patients at day 90 [9/14 (64%)]. Cosmesis was good and
scored similarly by physician and patient at day 90 (P = 0.313).
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Assessment type |
Systematic | ||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||
Dictionary version |
6
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Reporting groups
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Reporting group title |
Patients
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Reporting group description |
- | ||||||||||
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Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||
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Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Patient-reported AEs were mostly moderate siterelated pain and mild pruritus. Clinical scarring in terms of skin structural and pigmentation changes was observed in majority of cleared patients at day 90 [9/14 (64%)]. Cosmesis was good and scored similarly by physician and patient at day 90 (P = 0.313). |
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
Limitations of the study included the uncontrolled design, the limited sample size, different numbers of evaluated subtypes, and only 3-month follow-up. OCT assessments of BCC thickness were not included in the protocol, which may be considered | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/31442334 |