Overview

This trial has been completed.

Condition actinic keratosis
Treatments pretreatment with co2 laser before photodynamic therapy, only photodynamic therapy
Sponsor Oslo University Hospital
Start date August 2013
End date September 2016
Trial size 12 participants
Trial identifier NCT01898936, Transplant heads

Summary

Organ transplant recipients (OTR) have an increased risk of non-melanoma skin cancer, in particular squamous cell carcinoma (SCC), often developing in areas of field cancerization, areas with multiple precancerous actinic keratoses. The risk of developing SCC in OTR is 65-100-fold the normal population (Jensen 1999, Lindeløf 2000), and this cancer often runs a more aggressive course with metastasis reported to occur in 5-8% of cases (Berg 2002). The treatment options in field cancerization are limited. In Norway, the registered treatment alternatives are the topical immune response modifier imiquimod and photodynamic treatment. Neither of these treatments has shown long term beneficial effects.

In this study, we will study the effect of pre-treating the skin with ablative, fractional carbondioxide laser before photodynamic therapy in a group of OTR with multiple actinic keratoses

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
The treatment will be a field treatment performed with a 30 W Lutronic carbondioxide laser; covering one of the symmetrical treatment areas allocated to fractional carbondioxide laser. The laser settings will be as follows: The fluence will initially be 10mJ/cm2 delivered with a 120 micron tip (producing 120 micron ablative columns) with 5% density. The fluence will be increased until the patient experiences pain (pain indicating penetration to dermis), and then reduced to maximum fluence without pain. Allocation to laser therapy is blinded for the future evaluato
pretreatment with co2 laser before photodynamic therapy
The treatment will be a field treatment performed with a 30 W Lutronic carbondioxide laser; covering one of the symmetrical treatment areas allocated to fractional carbondioxide laser. The laser settings will be as follows: The fluence will initially be 10mJ/cm2 delivered with a 120 micron tip (producing 120 micron ablative columns) with 5% density. The fluence will be increased until the patient experiences pain (pain indicating penetration to dermis), and then reduced to maximum fluence without pain. Allocation to laser therapy is blinded for the future evaluator. The PDT procedure includes application of Metvix cream on the skin on both symmetrical areas with a thickness of approximately 1 mm, plastic covering for 30 minutes before entering daylight for 2 hours.
(Sham Comparator)
This group will not get pretreatment with CO2 laser
only photodynamic therapy
After curettage/debulking, the BCC is incubated with MAL cream (Metvix® cream, Galderma, France), occluded for three hours under a plastic film and illuminated with red light-emitting diode light (LED) at 632 nm at a dosage of 37 J/cm2 (Aktilite®, Galderma, Oslo, Norway).

Primary Outcomes

Measure
Lesion response rate defined as fraction of lesions with a complete response to treatment
time frame: 12 months

Secondary Outcomes

Measure
Adverse effects with emphasis on pain during illumination and following days; erythema, crusting and pustules and long-term pigmentary changes and scars.
time frame: 1 week and 12 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Multiple actinic keratoses (>5) in two symmetrical areas on each side of the scalp or forehead - OTR with stable graft function - More than eighteen years of age - Written informed consent Exclusion Criteria: - Allergy to the MetvixR cream - Previous PDT treatment less than 6 months ago in treatment areas - Infiltrating tumor in treatment areas - Porphyria - Known tendency to produce hypertrophic scars and keloids

Additional Information

Official title A Randomized Half-side Comparative Trial of Fractional Laser-assisted Daylight Photodynamic Therapy Versus Daylight Photodynamic Therapy in Organ Transplant Recipients With Multiple Actinic Keratoses of the Scalp or Forehead
Description Protocol for the study: "A randomized half-side comparative trial of fractional laser-assisted daylight photodynamic therapy versus daylight photodynamic therapy in organ transplant recipients with multiple actinic keratoses of the scalp or forehead" Organ transplant recipients (OTR) have an increased risk of non-melanoma skin cancer, in particular squamous cell carcinoma (SCC), often developing in areas of field cancerization, areas with multiple precancerous actinic keratoses. The risk of developing SCC in OTR is 65-100-fold the normal population (Jensen 1999, Lindeløf 2000), and this cancer often runs a more aggressive course with metastasis reported to occur in 5-8% of cases (Berg 2002). The treatment options in field cancerization are limited. In Norway, the registered treatment alternatives are the topical immune response modifier imiquimod and photodynamic treatment. Neither of these treatments has shown long term beneficial effects. Photodynamic treatment (PDT) is a treatment that selectively targets abnormal cells, through radical oxygen species (ROS) generated by photosensitizers activated by visible light. Activation by light can be performed with lamps (LED lamps) or by daylight. Daylight-PDT is shown to be less painful than PDT performed with lamps (Wiegell 2008). The photosensitizer is applied directly on the skin surface after careful removal of hyperkeratosis. PDT is shown to be effective in treating epithelial dysplasia in the immunocompetent population, with clearance rates of 71-100% for facial and scalp keratosis, and 44-73% on acral sites (Morton 2002). The lesser effectiveness on extremities is possibly due to more hyperkeratosis on extremities with less absorption of the cream. PDT is shown to be less effective in the transplant population compared to the non-immunosuppressed (Dragieva 2004, Morton 2008). The reason is most likely multifactorial, but the thickness of the hyperkeratotic layer is regarded as an important factor. In animal models as well as in humans, it has been shown by fluorescence measurements that ablative fractional laser treatment facilitates delivery of the photosensitizing cream deeply into the skin (Haedersdal 2010, Togsverd-Bo 2012). The laser ablates columns of skin, facilitating penetration and thereby increasing the absorption of the drug to deeper layers. In this study, we will study the effect of pre-treating the skin with ablative, fractional carbondioxide laser before PDT in a group of OTR with multiple actinic keratoses. Two symmetrical areas of the scalp or forehead will be randomized and one side will be allocated to receive fractional ablative carbondioxide laser treatment. Both symmetrical areas will then receive daylight PDT. The primary endpoints will be a comparison of the fraction of lesions with a complete response to treatment (CR). Secondary endpoints will be graded treatment response and adverse effects to treatment; both acute (pain) and long-term (scars and pigmentary changes). The patients will be evaluated 4 and 12 months after the treatment procedure. For a detailed description of the procedure, see below. Study design: This is a randomized, two-treatment half-side comparative study of daylight PDT with or without ablative fractional carbondioxide laser with blinded treatment assessment. The study will compare both efficacy and tolerability of one treatment of fractional laser assisted daylight-PDT versus daylight-PDT only treating multiple actinic keratoses in two symmetrical areas of the scalp or forehead in organ transplant recipients. The patients will be pre-treated with removal of thick keratoses (grade 2 and 3) from both sides of scalp or forehead one week before randomization and treatment. After randomization, one side will be allocated to treatment with ablative fractional carbondioxide laser and daylight PDT; the other side will receive daylight-PDT only. Pain will be evaluated with a VAS score after 2 hours in daylight, and patients will be instructed to repeat this score evaluating pain in treatment areas the successive days after treatment, and report this when contacted by phone after one week. Patient population: 15 OTR Randomization procedure: Randomization is performed immediately before the fractional laser procedure from a computer generated list and allocation is concealed by drawing lots of sealed, opaque envelopes Treatment procedures: After written informed consent patients are offered removal of superficial hyperkeratosis by curettage and/or keratolytic cream one week before inclusion in the study. Two symmetrical treatment areas in either scalp or forehead are marked with a pen, photographed and long hair will be cut in the treatment areas. Actinic keratoses will be registered and graded according to Olsen (Olsen 1991). Treatment areas will then covered with plastic and marked with areas to be treated and the keratotic lesions (with grading). The plastics will be saved/transferred to paper and saved. The treatment will be a field treatment performed with a 30 W Lutronic carbondioxide laser; covering one of the symmetrical treatment areas allocated to fractional carbondioxide laser. The laser settings will be as follows: The fluence will initially be 10mJ/cm2 delivered with a 120 micron tip (producing 120 micron ablative columns) with 5% density. The fluence will be increased until the patient experiences pain (pain indicating penetration to dermis), and then reduced to maximum fluence without pain. Allocation to laser therapy is blinded for the future evaluator. The PDT procedure includes application of Metvix cream on the skin on both symmetrical areas with a thickness of approximately 1 mm, plastic covering for 30 minutes before entering daylight for 2 hours. The treatment procedure will produce a skin barrier defect, and all patients will receive systemically administered antibiotic the treatment day and additional 4 days for a total of 5 days to prevent a skin infection, taking into account all other systemic medications and organ function. The patient will return the treatment site after daylight exposure to register immediate adverse events (pain) and will be contacted by phone 1 week after the treatment procedure to evaluate adverse effects the days after treatment. Blinded evaluation will be performed at 4 and 12 months after the treatment procedure, and will include registration and grading of actinic keratoses in the treatment areas (treatment efficacy) and registration of adverse events (scars and pigmentary changes). Evaluation will be supported by pre-treatment photographs and plastics with drawings. Efficacy evaluation Patients will be evaluated at 4 and 12 months by an investigator blinded to which side was allocated to assisted ablative fractional laser treatment. Statistics Wilcoxon matched pairs signed rank test will be used to compare paired data. This study is investigator initiated and independently financed by Oslo University Hospital- Rikshospitalet
Trial information was received from ClinicalTrials.gov and was last updated in December 2016.
Information provided to ClinicalTrials.gov by Oslo University Hospital.