Efficacy of Ingenol Mebutate on Actinic Keratoses and Field Cancerization vs Cryotherapy

NCT02990221 | Completed Phase 4 DMC

• 1 other identifier: IIS-PICATO 1264
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The main objective of this study is to compare the effectiveness of ingenol mebutate gel (150 mcg / g per day, to be applied on a predetermined area of 25 cm2 of skin of the face or scalp, for 3 days consecutive) cryotherapy (application with 5 seconds of freezing time of each lesion located in a predetermined skin area of 25 cm2 of the face or scalp) in the treatment of actinic keratosis and their field cancerization. Study details: This study is randomized. 50 subjects with at least two actinic keratoses of grade I and II, located in two different districts of 25 cm2 skin of the face or scalp, and who meet all the inclusion criteria will be enrolled in the study by the investigators in the three different centers mentioned above. The investigators will assess the effect of treatment by confocal microscopy and digital dermoscopy. The investigator will acquire images of selected areas of the face and scalp before and after treatment. Data will be collected and analyzed by the coordinating centre. Procedure for the study: Recruitment of subjects; random assignment of treatment (ingenol mebutate gel 150 micrograms/g and cryotherapy) to the two skin areas of 25 cm2 of the subject recruited; evaluation of the two areas with reflectance confocal microscopy and digital dermoscope. The measurements will be carried out at time 0, after 1 month and 6 months. The investigator must fill out a form for each subject at the beginning (day 0), after 1 month and at the end of the study (after 6 months). The subject must complete a questionnaire at the beginning (day 0), after 1 month and at the last follow-up visit (after 6 months). Measurement parameters: Dermoscopy and confocal microscopy will be used to assess the percentage reduction in actinic keratoses and the damage of the cancerous area in the two selected areas treated with ingenol mebutate gel or cryotherapy, respectively. Adverse / side events will be collected at each visit by the investigator and will be contained in another form.

Conditions

Actinic Keratosis

Keywords

Field Cancerization

Outcome Measures

Primary Outcomes (2)

• At least 75% reduction in the total AK count relative to baseline

  The primary efficacy endpoint is the percentage change, at the end of the treatment period, in the number of AK lesions that were originally defined in the selected AK target area at baseline. The percentage change in the number of AK lesions is calculated as the number of lesions present at the end of the treatment period in the target area minus the number of AK lesions present in the target area at baseline visit divided by the number of lesions present in the target area at baseline. This variable will be analysed using a non-parametric analysis (Wilcoxon Rank-sum test).

  6-month follow-up

• Reduction of subclinical AK lesions according to a Reflectance Confocal Microscopy score

  Change from baseline in RCM score of target area and RCM score of cancerization field at the end of the treatment period. Each of the 13 RCM criteria will be scored 0 (absent), 1 (\<25%), 2 (25%-50%), 3 (50-75%), or 4(\>75%). An overall score will be obtained by averaging the RCM scores at the epidermal, DEJ and dermal level. The same approach will be used for the RCM examination of the cancerization field. The above variables will be compared between the groups using a t-test, 95% confidence interval for the between-group difference will be provided.

  6-month follow-up

Secondary Outcomes (2)

• Absence of new lesions after a follow-up period of 6 months

  6-month follow-up

• cosmetic outcome

  6-month follow-up

Study Arms (2)

Ingenol mebutate

ACTIVE COMPARATOR

application of ingenol mebutate for 3 consecutive days on an area of face/scalp of 25 cm2

Drug: Ingenol mebutate

cryotherapy

ACTIVE COMPARATOR

application of criotherapy on actinic keratosis present in an area of face/scalp of 25 cm2 different from the ingenol mebutate area

Procedure: cryotherapy

Interventions

Ingenol mebutate DRUG

150 mcg / g per day, to be applied on a predetermined area of 25 cm2 of skin of the face or scalp, for 3 days consecutive

Also known as: Picato

Ingenol mebutate

cryotherapy PROCEDURE

application with 5 seconds of freezing time of each lesion located in a predetermined skin area of 25 cm2 of the face or scalp

Also known as: cryosurgery

cryotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Current diagnosis of AK, with ≥2 lesions of grade I and/or II located in two different anatomical districts (within a contiguous 25 cm2 area on the face, scalp or forehead);
• Male ≥ 18 years of age or Female \> 60 years of age;
• Skin type I or II according to Fitzpatrick;
• Patient has confirmed his/her willingness to participate in this study after being informed of all aspects of the study that are relevant to his/her decision to participate, by signing and dating the approved informed consent form, according to ICH and local laws.
• The 25 cm2 contiguous treatment areas could be of any shape, e.g. 5 cm x 5 cm, 2 cm x 12.5 cm, 3 cm x 8.3 cm.

You may not qualify if:

• Has received any therapy for AK within the past 3 months
• Has AK of grade III
• Has currently a skin cancer or shows an early stage of skin cancer;
• Has another skin disease that requires treatment with other medications in the AK area or in distance of 3 cm;
• Use of cosmetic or therapeutic products and procedures which could interfere with assessments of the treatment area;
• Immunosuppressive therapies or current treatment for cancer;
• Clinically unstable medical condition;
• High risk group for HIV infection or presentation of other infectious diseases (hepatitis A virus , hepatitis B virus , hepatitis C virus , Tuberculosis, etc);
• Allergies to the tested gel (ingenol mebutate and eccipients);
• Psychiatric disease that may interfere with follow-up of study procedures;
• Participation in other clinical trials up to 30 days prior to day 1 of the study;
• Patient is, for any reason, considered by the investigator to be an unsuitable candidate for the study.

Sponsors & Collaborators

• University of Campania Luigi Vanvitelli: lead

Study Sites (1)

Second University of Naples

Naples, 80131, Italy

Location

Related Publications (8)

• Frost CA, Green AC. Epidemiology of solar keratoses. Br J Dermatol. 1994 Oct;131(4):455-64. doi: 10.1111/j.1365-2133.1994.tb08544.x.

  PMID: 7947197 RESULT

• Fu W, Cockerell CJ. The actinic (solar) keratosis: a 21st-century perspective. Arch Dermatol. 2003 Jan;139(1):66-70. doi: 10.1001/archderm.139.1.66. No abstract available.

  PMID: 12533168 RESULT

• Ortonne JP. From actinic keratosis to squamous cell carcinoma. Br J Dermatol. 2002 Apr;146 Suppl 61:20-3. doi: 10.1046/j.1365-2133.146.s61.6.x.

  PMID: 11966728 RESULT

• Cohen JL. Actinic keratosis treatment as a key component of preventive strategies for nonmelanoma skin cancer. J Clin Aesthet Dermatol. 2010 Jun;3(6):39-44.

  PMID: 20725550 RESULT

• Padilla RS, Sebastian S, Jiang Z, Nindl I, Larson R. Gene expression patterns of normal human skin, actinic keratosis, and squamous cell carcinoma: a spectrum of disease progression. Arch Dermatol. 2010 Mar;146(3):288-93. doi: 10.1001/archdermatol.2009.378.

  PMID: 20231500 RESULT

• Vatve M, Ortonne JP, Birch-Machin MA, Gupta G. Management of field change in actinic keratosis. Br J Dermatol. 2007 Dec;157 Suppl 2:21-4. doi: 10.1111/j.1365-2133.2007.08268.x.

  PMID: 18067627 RESULT

• Fidler B, Goldberg T. Ingenol mebutate gel (picato): a novel agent for the treatment of actinic keratoses. P T. 2014 Jan;39(1):40-6.

  PMID: 24672213 RESULT

• Andrews MD. Cryosurgery for common skin conditions. Am Fam Physician. 2004 May 15;69(10):2365-72.

  PMID: 15168956 RESULT

MeSH Terms

Conditions

Keratosis, Actinic

Interventions

3-ingenyl angelate; Cryotherapy; Cryosurgery

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Keratosis; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Ablation Techniques; Surgical Procedures, Operative

Study Officials

• Giuseppe Argenziano, Prof

  University of Campania Luigi Vanvitelli

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 2, 2016
• First Posted: December 13, 2016
• Study Start: April 12, 2017
• Primary Completion: April 30, 2018
• Study Completion: July 30, 2018
• Last Updated: September 24, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)