Photodynamic Therapy (PDT) With Metvix® 160 Milligrams/Gram Cream in Organ Transplant Participants With Non-melanoma Skin Cancer

Phase 3

Completed

Conditions: Actinic Keratosis
Basal Cell Carcinoma
Warts
Bowens Disease
Squamous Cell Carcinoma

Registration Number: NCT00472459

Lead Sponsor: Galderma R&D

Brief Summary: Participants on immunosuppressive therapy, e.g., organ recipients, had higher occurrence of AK (Actinic Keratosis) than the untreated population. Keratotic lesions (i.e., AK lesions and warts) in this population were highly associated with development of SCC (Squamous Cell Carcinoma) also with 10 times higher mortality rate because of SCC than expected. The risk of developing skin cancer, predominantly SCC and BCC (Basal Cell Carcinoma), increased with graft survival time and the length of immunosuppressive treatment period.

The higher risk of developing skin malignancy and more aggressive skin malignancies in this population, indicated the need for early removal of these pre-malignant lesions.

In this study, two contralateral areas (5x10 cm\^2) with skin lesions within the participant were compared. One area was received Metvix PDT at defined intervals and the other was received lesion specific treatment at the discretion of the investigator. The primary endpoint was the accumulated number of new lesions during the study and number of AK lesions that showed complete response 3 months after baseline. Secondary endpoints were number of BCC lesions that showed complete response, number of recurrent lesions, assessment of cosmetic outcome and safety.

Detailed Description: The treatment area (5x10 cm\^2) was treated at baseline and at 3 ,9 and 15 months visits. At baseline, the area was treated with fractionated Metvix® PDT treatment consisting of two treatment one week apart and at 3 ,9 and 15 months visits with single Metvix® PDT treatment. The participants were evaluated for occurrence of new lesions, lesion response and recurrence at 3 (not recurrence),9,15,21, and 27 months visits. New and recurrent lesions in the treated area were treated with Metvix® PDT treatment. Lesions with partial response in the treated area were re-treated with Metvix® PDT and lesions with no response were treated with lesion specific treatment at the discretion of the investigator.

In the contralateral control area (5x10 cm\^2), new and recurrent lesions and lesions in non-complete response were treated with lesion specific treatment at the discretion of the investigator at each study visit.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 82

Inclusion Criteria

Transplant recipients with at least 2 clinically diagnosed AK lesion and maximum 10 skin lesions (AK, BCC, SCC in situ and/or warts) in each of the two contralateral areas (diameter 5x10^2 cm) in the face, the scalp, the extremities or on the trunk/neck.
Transplant recipients who previously were treated more than once for their skin lesions.
Transplant recipients who had received immunosuppressive therapy for more than 3 years.
Males or females above 18 years of age.
Written informed consent.

Exclusion Criteria

Participants with more than 10 skin lesions (AK, BCC, SCC in situ, warts) in one of the two areas.
Participants with SCC (not SCC in situ) in one of the two areas.
Participants not previously treated or treated only once for their skin lesions.
Participants with rosacea in one of the two areas.
Participants with morphea form/highly infiltrating BCC
Known allergy to methyl-amino levulinate, a similar compound or excipients of the cream
Participation in other clinical studies either concurrently or within the last 30 days.
Pregnant or breast-feeding (all women of child-bearing potential documented a negative pregnancy test and used the pill or IUD during the treatments and for at least one month thereafter).
Conditions associated with a risk of poor protocol compliance

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Number of Accumulated New Skin Lesions at Month 3	At Month 3	A new lesion was defined as a visible new lesion of any size after the Baseline. New skin lesions accumulated were sum of actinic keratoses (AK) lesions, basal cell carcinoma (BCC) lesions, squamous cell carcinoma (SCC) lesions and warts in treated area and contralateral control area (symmetrically). Number of accumulated new skin lesions at Month 3 were reported.
Number of Accumulated New Skin Lesions at Month 9	At Month 9	A new lesion was defined as a visible new lesion of any size after the Baseline. New skin lesions accumulated were sum of AK lesions, BCC lesions, SCC lesions and warts in treated area and contralateral control area (symmetrically). Number of accumulated new skin lesions at Month 9 were reported.
Number of Accumulated New Skin Lesions at Month 15	At Month 15	A new lesion was defined as a visible new lesion of any size after the Baseline. New skin lesions accumulated were sum of AK lesions, BCC lesions, SCC lesions and warts in treated area and contralateral control area (symmetrically). Number of accumulated new skin lesions at Month 15 were reported.
Number of Accumulated New Skin Lesions at Month 21	At Month 21	A new lesion was defined as a visible new lesion of any size after the Baseline. New skin lesions accumulated were sum of AK lesions, BCC lesions, SCC lesions and warts in treated area and contralateral control area (symmetrically). Number of accumulated new skin lesions at Month 21 were reported.
Number of Accumulated New Skin Lesions at Month 27	At Month 27	A new lesion was defined as a visible new lesion of any size after the Baseline. New skin lesions accumulated were sum of AK lesions, BCC lesions, SCC lesions and warts in treated area and contralateral control area (symmetrically). Number of accumulated new skin lesions at Month 27 were reported.
Number of AK Lesions That Showed Complete Response at Month 3	At Month 3	Complete response was defined as the complete disappearance of the lesion. The AK lesions were graded as grade 1(mild); slightly palpable AK, better felt than seen, grade 2 (moderate); moderately thick AK, easily felt and seen, and grade 3 (severe); very thick and/or obvious AK. Mantel-Haenszel weighted difference was used to calculate number of AK lesions that showed complete response.
Number of AK Lesions That Showed Complete Response at Month 9	At Month 9	Complete response was defined as the complete disappearance of the lesion. The AK lesions were graded as grade 1(mild); slightly palpable AK, better felt than seen, grade 2 (moderate); moderately thick AK, easily felt and seen, and grade 3 (severe); very thick and/or obvious AK. Mantel-Haenszel weighted difference was used to calculate number of AK lesions that showed complete response.
Number of AK Lesions That Showed Complete Response at Month 15	At Month 15	Complete response was defined as the complete disappearance of the lesion. The AK lesions were graded as grade 1(mild); slightly palpable AK, better felt than seen, grade 2 (moderate); moderately thick AK, easily felt and seen, and grade 3 (severe); very thick and/or obvious AK. Mantel-Haenszel weighted difference was used to calculate number of AK lesions that showed complete response.
Number of AK Lesions That Showed Complete Response at Month 21	At Month 21	Complete response was defined as the complete disappearance of the lesion. The AK lesions were graded as grade 1(mild); slightly palpable AK, better felt than seen, grade 2 (moderate); moderately thick AK, easily felt and seen, and grade 3 (severe); very thick and/or obvious AK. Mantel-Haenszel weighted difference was used to calculate number of AK lesions that showed complete response.
Number of AK Lesions That Showed Complete Response at Month 27	At Month 27	Complete response was defined as the complete disappearance of the lesion. The AK lesions were graded as grade 1(mild); slightly palpable AK, better felt than seen, grade 2 (moderate); moderately thick AK, easily felt and seen, and grade 3 (severe); very thick and/or obvious AK. Mantel-Haenszel weighted difference was used to calculate number of AK lesions that showed complete response.

Secondary Outcome Measures

Name	Time	Method
Number of BCC Lesions That Showed Complete Response	At Months 3, 9, 15, 21 and 27	Complete response was defined as the complete disappearance of the lesion. BCC lesions were characterized as superficial: ill-defined red scaly macule; could increase in size to form crusted, occasionally ulcerated, scaly erythematous patches, but never indurated and nodular: flesh-colored, cream to pink, waxy papule with prominent surface telangiectasias; as the lesions grow, central erosion or ulceration and crusting occur, surrounded by a pearly, rolled, translucent border. Number of BCC lesions that showed complete response was reported.
Number of Recurrent Lesions	At Months 9, 15, 21 and 27	Recurrence of lesions was defined as reappearance of previously treated and eradicated lesions and was verified by histology in accordance with local hospital practice.
Number of Participants With Overall Cosmetic Outcome Assessed by Investigator and Participants	At Month 27	Overall cosmetic outcome for the two contralateral areas (treatment and contralateral control) with an area of 5 by 10 cm\^2 was assessed with regards to either absence or presence of all signs or symptoms or the presence of at least one of the signs or symptoms; scarring, atrophy, depigmentation, redness and fibrosis by both investigator and participant. Parameters were assessed for each area were hypopigmentation, hyperpigmentation, scar formation and tissue defect. The occurrence of these parameters was graded as none, slight, or obvious. Cosmetic outcome was presented as number of participants in each category (none, slight, obvious) for each variable assessed (hypopigmentation, hyperpigmentation, scar formation, tissue defect).
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	From Baseline up to Month 27	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Trial Locations

Locations (11): Department of Dermatology, Roskilde Amysygehus
🇩🇰
Roskilde, Denmark
Department of Dermatology, Århus Amysygehus
🇩🇰
Århus, Denmark
Klinik für Dermatologie, Venerologie und Allergologie, Campus Charité Mitte
🇩🇪
Berlin, Germany
Hautklinik Linden
🇩🇪
Hannover, Germany
Department of Dermatology, Rikshospitalet
🇳🇴
Oslo, Norway
Department of Dermatology, St. Olavs Hospital
🇳🇴
Trondheim, Norway
Department of Dermatology, Sahlgrenska University Hospital
🇸🇪
Gothenburg, Sweden
Department of Dermatology, Karolinska University Hospital, Huddinge
🇸🇪
Stockholm, Sweden
Department of Dermatology, Uppsala University Hospital
🇸🇪
Uppsala, Sweden
Dermatology Department, Manchester Royal Infirmary
🇬🇧
Manchester, United Kingdom
Portsmouth Dermatology Centre, St Mary's Hospital
🇬🇧
Portsmouth, United Kingdom