Metvix PDT Versus Cryotherapy in Patients With Primary Superficial Basal Cell Carcinoma

The purpose of this study is to compare the efficacy of Photodynamic Therapy (PDT) with methyl aminolevulinate (MAL) cream to cryotherapy, in treatment of patients with primary superficial basal cell carcinoma.

Secondary objectives are to compare cosmetic outcome and tolerability (adverse events) in these patients, 3 months after treatment. In addition the recurrence rates in the two treatment groups will be compared up to five years after treatment.

BCC is a highly frequent skin malignancy, and accounts for approximately 75% of all non-melanoma skin cancers. It is the most common malignant tumour of any organ, mostly affecting head and neck (84%) in fair-skinned people. Several non-pharmacological treatment modalities are used for BCC, including excision surgery, Moh's surgery, radiation, curettage/electrodesiccation and cryotherapy. The treatment used depends on the type, size, depth and localisation of the BCC lesion.

The use of PDT is attractive for the treatment of BCCs because of its efficiency, mild and local side effects and excellent cosmetic outcome. Previous clinical experience is promising and patients with primary BCCs will be included in this prospective, randomised, comparative, multicenter study to show that Metvix is non-inferior to alternative treatment with better cosmetic outcome.

The primary end-point will be the number of patients in whom 75% or more of the BCC lesions have responded completely at 3 months after PDT with Metvix or 3 months after cryotherapy. Both on-site and independent, blinded response assessments will be analysed. The analysis based on the results of the independent review board constitutes the primary analysis.

The secondary end-points will be the proportion of patients in whom less than 75% of the BCC lesions respond completely, number of lesions across patients that show complete response, evaluation of cosmetic outcome and adverse events 3 months after Metvix PDT or 3 months after cryotherapy. In addition 12, 24, 36, 48 and 60 months recurrence rates will be assessed.

Inclusion Criteria:

A patient with superficial BCC lesion(s) suitable for entry was defined as a patient with:

• histologically confirmed diagnosis of primary superficial BCC lesion(s)
• BCC lesions suitable for cryotherapy
• males or females above 18 years of age
• written informed consent. In accordance with Amendment 2 (local amendment), only patients above 19 years of age were to be included in Austria.

Exclusion Criteria:

A patient or lesion fulfilling any of the following criteria was ineligible for inclusion:

• prior treatment of the BCC lesion(s)
• patients with more than 10 eligible BCC lesions
• a superficial BCC lesion with the largest diameter exceeding 15 mm on face/scalp, larger than 20 mm on extremities and neck and larger than 30 mm on the trunk
• a superficial BCC lesion with the largest diameter smaller than 6 mm
• patient with porphyria
• patient with Gorlin's syndrome
• pigmented superficial BCC lesion(s)
• morpheaform lesion(s)
• infiltrating lesion(s)
• patients with a history of arsenic exposure
• 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 had to document a negative pregnancy test and use the pill or intrauterine device during the treatments and for at least one month thereafter
• conditions associated with a risk of poor protocol compliance.

In Amendment 1 the following exclusion criteria were added:

• xeroderma pigmentosum lesion
• concurrent use of immunosuppressive medication.