The variable “complete response” after one or two Metvix treatment cycles will be used as the basis for the justification of sample size. The following hypothesis will be tested:
H0: Complete response rate of Metvix is less or equal to 65% versus the alternative hypothesis HA: Complete response rate of Metvix is greater than 65%

Official Title

An Open Multicenter, Phase III Study of Photodynamic Therapy With Metvix Cream 160 mg/g in Patients With “High Risk” Basal Cell Carcinoma

Conditions

Basal Cell Carcinoma

Study Type

Interventional

Study Design

Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Further Details

Primary Outcome Measures:

  • The primary end-point will be the histologically confirmed complete response rate within a patient (No BCC cells in the biopsy taken 3 months after the last treatment). [Time Frame: 3 months after last treatment]

Secondary Outcome Measures:

  • Safety evaluation during the first 13 weeks or 6 months (if two treatment cycles) after the first Metvix treatment [Time Frame: 13 weeks or 6 months after first freatment]
  • Cosmetic outcome [Time Frame: 12, 24, 36, 48 and 60 months after the first treatment]
  • Recurrence rate [Time Frame: 12, 24, 36, 48 and 60 months after the first treatment]

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 photoactive porphyrins. 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 . BCC is a highly frequent skin malignancy, and accounts for approximately 75% of all non-melanoma skin cancers . It is the most common cancer in humans . Several non-pharmacological treatment modalities are used for BCC, including excision surgery, curettage and electrodesiccation, cryosurgery and more advanced modalities like radiation therapy, plastic surgery with reconstruction and Moh’s surgery. The treatment used depends on the type, size, depth and localisation of the BCC lesion. Treatment options for BCC give good response rates in the majority of patients but are inadequate in a small group of patients defined as “high-risk” BCC. In this particular patient group, even a moderate complete response rate with good cosmetic results may be considered beneficial, since the number of patients who have to receive more advanced therapy with the possibility of high morbidity and poor cosmetic outcome will be reduced. Even a partial response is of clinical interest since the remaining tumour will require less extensive surgery. In the case of treatment failure, Metvix PDT does not interfere with the use of other treatment modalities.

Study Start

September 2000; Study completion: June 2006

Eligibility & Criteria

  • Ages Eligible for Study: 18 Years and above
  • Genders Eligible for Study: Both

Inclusion Criteria:

  • Clinical diagnosis of BCC lesions verified by histology (2-3 mm punch biopsy)
  • Males or females above 18 years of age.
  • Written informed consent. AND
    • Patients with high risk of surgical complications due to:
      • Anticoagulant medication or bleeding disorders
      • Cardiac risk factors
      • Anaesthetic contraindications
      • Poor surgical compliance because of patient refusal, dementia, or inability to perform wound care.
      • OR

      • Patients with “high-risk” BCC lesion(s). A “high-risk” BCC lesion is defined as a large BCC lesion with the largest diameter:
        • Equal to or greater than 15 mm on extremities, except below the knees, where largest diameter should be equal to or greater than 10 mm
        • Equal to or greater than 20 mm on the trunk
        • Equal to or greater than 15 mm in the face, or A lesion in the mid-face region (H-zone according to Swanson) or on the ear In patients with more then 6 eligible lesions, the 6 lesions to be treated will be randomly chosen.

    Exclusion Criteria:

    • Prior treatment of the lesion within 4 weeks.
    • A pure morpheaform and/or highly infiltrated lesion assessed clinically and/or by histology. A mixed nodular/morpheaform lesion which is not highly infiltrated (clinically) may be included.
    • Patient with porphyria.
    • Pigmented lesions.
    • Known allergy to ‘Metvix’ or a similar compound.
    • Participation in another clinical study either concurrently or within the last 30 days
    • Patient with Gorlin’s syndrome.
    • Patient with Xeroderma pigmentosum
    • Pregnant or breast-feeding (all women of child-bearing potential must document a negative pregnancy test and use contraception during the treatments and for at least one month thereafter).
    • Conditions associated with a risk of poor protocol compliance.

    Total Enrolment

    102

    Contact Details

    New South Wales

    • Department of Dermatology, St. George Hospital, Kogarah, New South Wales, NSW 2217, Australia

    Queensland

    • South East Dermatology, The Belmont Specialist Clinic, Carnia, Queensland, 4152, Australia

    South Australia

    • Dermatology Department, The Queen Elisabeth Hospital, Adelaide, South Australia, SA 5011, Australia
    • Department of Dermatology, Royal Adelaide Hospital, Adelaide, South Australia, SA 5000, Australia

    Victoria

    • Clinic B, Repatriation Campus, Austin & Repatriation Medical Centre, Heidelberg, Victoria, VIC 3081, Australia

    Western Australia

    • Dermatology Surgery & Laser Centre, The Perth Surgicentre, Perth, Western Australia, WA 6151, Australia
    • Fremantle Dermatology, Fremantle, Western Australia, WA 6106, Australia