Effect of Topical Imiquimod on Lentigo Maligna

Study Overview
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Brief Summary
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The purpose of this study is to determine if topical imiquimod is effective in the pathological complete regression of lentigo maligna.

Official Title
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Effect of Topical Imiquimod on Lentigo Maligna

Conditions
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Lentigo Maligna

Intervention / Treatment
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* Drug: Imiquimod


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of lentigo maligna (LM) (acquired pigmented macule present for more than 12 months with no change in skin surface texture or contour, no palpability, diameter >10 mm, sited on the head or neck). The lower anatomical limit is the root of the neck - a line joining the medial end of the clavicles with the medial insertion of trapezius. Histological findings consistent with LM (increased numbers of atypical melanocytes confined to the epidermis, sun damaged skin) in one or more 4mm punch biopsies(s) from the darkest area, reported by a pathologist with expertise in the diagnosis of melanocytic lesions, and part of a recognised NHS skin cancer Multi-Disciplinary Team. The upper limit of the lesion is not defined by size, but it must be suitable for complete surgical excision using a 5 mm lateral margin. The outline of the lesion must be easily defined visually in daylight around its entire circumference. Patient fit enough and willing to undergo surgery as required by the protocol. Exclusion Criteria: Clinical or histological evidence of invasive melanoma including any palpability of the lesion, or clinical and/or histological evidence of regression or dermal invasion Aged less than 45 years Recurrent LM - the index lesion must not have been previously treated Life expectancy of less than 12 months Other skin lesions which may compromise the ability to complete this study, such as co-existing or adjacent melanoma or non-melanoma skin cancer. Co-existing adjacent actinic keratoses would not exclude the patient from the study Women of childbearing potential, who are pregnant, plan to become pregnant during their study participation or breastfeeding. Unable to give informed consent. Hypersensitivity to imiquimod or to any of the excipients (methylhydroxybenzoate (E218), propylhydroxybenzoate (E216), cetyl alcohol and stearyl alcohol). Taking immunosuppressive medication. Taking part in any other intervention study.

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Imiquimod|250mg sachets to be applied at a start dose of 5 days a week. Dose will be adjusted using an algorithm according to tolerability.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological complete regression (PCR) in the mapped biopsied and resected LM using 2 mm slices. |  | Results available at 1-2 week post surgery follow up visit. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical assessment of response after imiquimod treatment | The pathological response in the entire resected lesion will be compared with that predicted from clinical examination and biopsies taken before surgery, post imiquimod treatment. We will assess whether adequate surgical margins can be determined using clinical maps. It is essential to know the accuracy of the method of clinical assessment of response. | Assessed at 12 week treatment visit and 1-2 week post surgery follow up | 
| Clinical feasibility of imiquimod treatment | Number of reported local adverse reactions and systemic adverse reactions; adherence to treatment schedule and acceptability of imiquimod treatment. | Tolerability will be assessed during treatment period of 12 weeks | 
| Number of consultations with NHS staff during imiquimod treatment |  | Assessed up to week 12 visit | 
| Frequency of functional T cell responses recognising peptide epitopes in melanocyte differentiation and cancer-testis antigens. | Circulating immune responses to proteins expressed within melanoma will be measured using blood draws taken before imiquimod treatment and after completion of imiquimod therapy but before surgery. The demonstration of a circulating immune response would be an important finding that would strongly support the investigation of imiquimod as primary therapy for melanoma, even if coupled with subsequent surgery because of the potential for such an immune response to be preventative against recurrence or invasive disease. | Assessed with baseline and 12 week visit samples. | 
| Measurement of hypothetical treatment preferences for surgery or imiquimod for LM using standard gamble technique. |  | Questionnaire completed at 12 weeks post surgery (follow up visit) |