Safety and Efficacy Study for the Treatment of Non-Aggressive Basal Cell Carcinoma With Photodynamic Therapy

A Randomized, Observer Blind, Multinational Phase III Study to Evaluate the Safety and Efficacy of BF-200 ALA (Ameluz®) in Comparison to Metvix® in the Treatment of Non-aggressive Basal Cell Carcinoma (BCC) With Photodynamic Therapy (PDT)

The aim of this study is to test the effectiveness and safety of the medicine Ameluz® (5-aminolevulinic acid) in comparison to methyl-aminolevulinate (MAL), used with photodynamic therapy (PDT), to treat thin, non-aggressive BCC (basal cell carcinoma).

The treatment comprises of up to 2 PDT cycles, each with two PDT sessions one week apart.

If 12 weeks after the the second PDT all lesions are completely cleared the patient will enter the follow-up phase. In case of remaining lesions the patient will receive a second PDT cycle starting on the same day.

Main Inclusion Criteria:

• Willing and able to sign informed consent form; obtained in writing before starting any study procedures
• Presence of 1-3 thin (≤2 mm thickness), clinically non-aggressive, primary BCC lesions (primary superficial, nodular, or mixed superficial/nodular) in the face/forehead, bald scalp, extremities and/or neck/trunk. Confirmation of non-aggressiveness and thickness of BCC through biopsies taken at screening for at least one lesion. Lesions non-eligible according to biopsy should timely be removed by surgery or cryotherapy
• Diameters of lesions should range between ≥0.5cm and ≤2cm; total maximal treated area is 10cm² (including 0.5-1.0cm margin surrounding each lesion)
• Target BCC lesions must be discrete and quantifiable and have to be located within 1-2 treatment areas
• Free of significant physical abnormalities (eg tattoos, dermatoses) in potential treatment area that may cause difficulty with examination or final evaluation
• Accept to abstain from extensive sunbathing and use of solarium during observer blind part. Patients with sunburn within treatment areas cannot be included until fully recovered
• Healthy patients and patients with clinically stable medical conditions, including, but not limited to controlled hypertension, diabetes mellitus type II, hypercholesterolemia, and osteoarthritis, will be permitted to be included in study if their medication is not prohibited by protocol
• Women of childbearing potential are permitted to participate in study only if they have a negative serum pregnancy test at screening and willingness to use a highly effective method of contraception during observer blind part

Main Exclusion Criteria:

• History of hypersensitivity to 5-ALA or any ingredient of BF-200 ALA, MAL or any ingredient of Metvix®, including arachis oil, or to peanut or soya

• Hypersensitivity to porphyrins

• Current treatment with immunosuppression therapy

• Presence of porphyria

• Presence of BCC lesions on embryonic fusion planes (H-zone)

• Presence of more than 3 BCCs

• Presence of malignant or benign tumors of the skin other than non-aggressive BCC within the treatment area (eg malignant melanoma, squamous cell carcinoma (SCC), aggressive BCC clinically diagnosed at screening) within the last 12 weeks

• Gorlin Syndrome or Xeroderma pigmentosum

• Presence of photodermatoses

• Treatment of lesions (actinic keratosis (AK), BCC, SCC, Bowens disease, melanoma) ≤12 weeks prior to first PDT, except physical treatments (eg cryosurgery, excision surgery) that will not be allowed ≤6 weeks prior to first PDT (Visit 2). Lesion(s) that seemed eligible clinically which could not be confirmed by biopsy, and which are located ≥10cm to an eligible lesion should timely be removed physically only

• Presence of inherited or acquired coagulation defect

• Start of intake of medication with hypericin or systemically-acting drugs with phototoxic or photoallergic potential within 8 weeks prior to screening

• Clinically relevant cardiovascular, hepatic, renal, neurologic, endocrine, or other major systemic disease making implementation of protocol or interpretation of study results difficult

• Evidence of clinically significant (CS), unstable medical conditions, eg:

  • Metastatic tumor or tumor with high probability of metastasis
  • Cardiovascular disease (New York Heart Association [NYHA] class III, IV)
  • Immunosuppressive condition
  • Hematologic, hepatic, renal, neurologic, or endocrine condition
  • Collagen-vascular condition
  • Gastrointestinal condition

• Topical treatment with 5-ALA or MAL outside treatment area during the observer blind part

• Any topical treatment including diclofenac and immunomodulatory agents (eg imiquimod, ingenol mebutate) 12 weeks prior to first PDT session and during observer blind part

• Any physical treatment during the observer blind part within treated target areas with exception of lesion(s) determined non-eligible by biopsy