Photodynamic Therapy (PDT) With Metvix Cream 160 mg/g Versus PDT With Placebo Cream in Patients With Primary Nodular Basal Cell Carcinoma

Study Overview
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Brief Summary
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Photodynamic therapy (PDT) is the selective destruction of abnormal cells through light activation of a photosensitiser in the presence of oxygen. These cells accumulate more photosensitiser than normal cells. The photosensitiser generates reactive oxygen species upon illumination. For skin diseases, there has been an increasing interest in using precursors of the endogenous photosensitiser protoporphyrin IX (PpIX). The most commonly used precursors have been 5-aminolevulinic acid (ALA) and its derivatives. The present test drug, Metvix, contains the methyl ester of ALA, which penetrates the lesions well and shows high lesion selectivity. In vitro studies of animal and human tissues have shown significant intracellular formation of photoactive porphyrins after addition of Metvix. The increased photoactive porphyrins levels induced cytotoxic effects in tumour cells after photoactivation. The primary objective is to compare PDT with Metvix cream to PDT with placebo cream in terms of patient complete response rates based on histologically verified disappearance of the lesions at 6 months after last treatment cycle. Secondary objectives are to compare the two treatments in terms of histological and clinical mean patient response weighted by the number of lesions within a patient, lesion response rates across patients, clinical complete patient response, cosmetic outcome and adverse events.

Detailed Description
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A patient will be randomised to PDT with Metvix cream or PDT with placebo cream. All eligible BCC lesions within a patient will get the same treatment. All patients will get two consecutive treatments one week apart. At the 3-months follow-up visit, lesions with no clinical response or progression will be surgically excised. Lesions with partial response (50% or greater reduction on lesion area) will be re-treated; if they do not show complete response three months later, they will be surgically excised. Lesions with complete response will be surgically excised 6 months after the first or second PDT cycle. All excised tissue specimens will be histologically examined.

Official Title
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A Multicenter, Phase III, Double Blind Study of Photodynamic Therapy (PDT) With Metvix 160 mg/g Cream in Comparison to PDT With Placebo Cream in Patients With Primary Nodular Basal Cell Carcinoma

Conditions
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Basal Cell Carcinoma

Intervention / Treatment
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* Procedure: PDT with Metvix 160 mg/g cream
* Procedure: PDT with placebo cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A patient with primary, nodular BCC lesion(s) suitable for entry is defined as a patient with Clinically diagnosed primary nodular BCC lesion(s) Histologically confirmed diagnosis of BCC BCC lesions suitable for simple excision surgery. Males or females above 18 years of age. Written informed consent Exclusion Criteria: A patient that is ineligible for inclusion is a patient fulfilling any of the following criteria: Patient with porphyria. Patient with Gorlin's syndrome. Patient with Xeroderma pigmentosum Patients concurrently receiving immunosuppressive medication Patients with a history of arsenic exposure. Patients with BCC arising in a previous radiated area Known allergy to Metvix, a similar PDT 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 must use adequate contraception (e.g. barrier methods, oral contraceptives or intrauterine device) during the treatment period and one month thereafter. In addition, they must have a negative pregnancy test prior to treatment.. Conditions associated with a risk of poor protocol compliance. Lesion Exclusion Criteria: A nodular BCC lesion in periorbital area, ears and nasolabial fold. A nodular BCC lesion with the longest diameter less than 6 mm or larger than 15 mm in face/scalp, larger than 20 mm on extremities and neck and larger than 30 mm on truncus. Pigmented nodular BCC lesion(s) Morpheaform nodular BCC lesion(s). Infiltrating nodular BCC lesion(s). Prior treatment of the BCC lesion(s).

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: PDT with Metvix 160 mg/g cream|nan|
|Procedure: PDT with placebo cream|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary end-point will be the histologically confirmed complete response rate within a patient (100% of the basal cell carcinoma [BCC] lesions must disappear completely). |  | 6 months after last treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histological and clinical mean patient response rates weighted for the number of lesions within a patient. |  | 3 and 6 months after last treatment | 
| Histological and clinical number of lesions across patients that show complete response |  | 3 and 6 months after last treatment | 
| Complete patient response |  | 3 and 6 months after last treatment | 
| Evaluation of cosmetic outcome. |  | 3 and 6 months after last treatment | 
| Adverse events |  | 2 weeks, 4 weeks and 3 months after each treatment cycle | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nodular Basal Cell Carcinoma, Basal Cell Carcinoma, PDT with Metvix 160 mg/g cream, PDT with placebo cream, Histological verification