Metvix PDT in Participant With "High Risk" Basal Cell Carcinoma

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

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 participants but are inadequate in a small group of participants defined as "high-risk" BCC.

In this particular participant group, even a moderate complete response rate with good cosmetic results may be considered beneficial, since the number of participant who have to receive more advanced therapy with the possibility of high morbidity and poor cosmetic outcome was reduced. Even a partial response is of clinical interest since the remaining tumour was require less extensive surgery. In the case of treatment failure, Metvix PDT does not interfere with the use of other treatment modalities.

The variable "complete response" after one or two Metvix treatment cycles was used as the basis for the justification of sample size.

Study Overview

• Status: Completed
• Conditions: Basal Cell Carcinoma
• Intervention / Treatment: Drug: Metvix® cream

Detailed Description

Prospective, open, multicenter study. The high risk BCC lesions were treated with Metvix cream. A biopsy confirming the diagnosis of each BCC lesion should have been taken within 6 months prior to treatment. The participants was receive one or two treatment cycles each consisting of two Metvix PDT treatments 7 days apart (Lesions that did not respond completely after three months received a second PDT treatment cycle).

The primary end-point was the histologically confirmed complete response rate within a participant (No BCC cells in the biopsy taken 3 months after the last treatment).

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, NSW 2217
      • Department of Dermatology, St. George Hospital
  • Queensland
    • Carnia, Queensland, Australia, 4152
      • South East Dermatology, The Belmont Specialist Clinic
  • South Australia
    • Adelaide, South Australia, Australia, SA 5000
      • Department of Dermatology, Royal Adelaide Hospital
    • Adelaide, South Australia, Australia, SA 5011
      • Dermatology Department, The Queen Elisabeth Hospital
  • Victoria
    • Heidelberg, Victoria, Australia, VIC 3081
      • Clinic B, Repatriation Campus, Austin & Repatriation Medical Centre
  • Western Australia
    • Fremantle, Western Australia, Australia, WA 6106
      • Fremantle Dermatology
    • Perth, Western Australia, Australia, WA 6151
      • Dermatology Surgery & Laser Centre, The Perth Surgicentre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Participants with high risk of surgical complications due to:

• Anticoagulant medication or bleeding disorders
• Cardiac risk factors
• Anaesthetic contraindications
• Poor surgical compliance because of participant refusal, dementia, or inability to perform wound care.

OR

• Participants 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 participants with more then 6 eligible lesions, the 6 lesions to be treated was 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.
• Participant 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
• Participant with Gorlin's syndrome.
• Participant 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metvix® PDT; Participants with basal cell carcinoma (BCC) lesions were administered to photodynamic therapy (PDT) with Metvix® cream 160 milligrams per gram (mg/g) applied for three hours, followed by illumination using non-coherent light with a fluency of 75 Joule per centimeter square (J/cm*2) and fluency rate of 70-200 milliwatt per centimeter square (mW/cm*2) up to 13 weeks.	Drug: Metvix® cream; Other Names: Methyl 5-aminolevulinate hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Histologically Confirmed Patient Complete Response (CR) 3 Months After Last Metvix PDT Cycle	Patient Complete Response (CR) was defined as 100 percentage of the lesions within the participant having negative findings for nodular basal cell carcinoma (BCC) in the histological examination.	3 months after last Metvix PDT cycle, up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Lesion With Complete Response 3 Months After Last Metvix PDT Cycle	Complete response was defined as no clinically visible BCC lesions in the treatment area.	3 months after last Metvix PDT cycle, up to 6 months
Overall Cosmetic Outcome Assessed by Investigator 3 Months After the Last Metvix PDT Cycle	Cosmetic outcome was assessed by both investigator and participants in participants with 100% of lesions in complete response. Overall cosmetic outcome was assessed with regard to occurrence of the following signs or symptoms; scarring, atrophy, induration, redness or change in pigmentation. The investigator graded the cosmetic outcome as: excellent: no scarring, atrophy or induration, and no or slight occurrence of redness or change in pigmentation compared lo adjacent skin; good: no scarring, atrophy or induration but moderate redness or change in pigmentation compared to adjacent skin; fair: slight to moderate occurrence of scarring, atrophy or induration; poor: extensive occurrence of scarring, atrophy or induration.	3 months after the last metvix PDT cycle, up to 6 months
Overall Cosmetic Outcome Assessed by Participants 3 Months After the Last Metvix PDT Cycle	Cosmetic outcome was assessed by both investigator and participants in participants with 100% of lesions in complete response. Overall cosmetic outcome was assessed with regard to occurrence of the following signs or symptoms; scarring, atrophy, induration, redness or change in pigmentation. The participants graded the cosmetic outcome as: excellent: no scarring, atrophy or induration, and no or slight occurrence of redness or change in pigmentation compared lo adjacent skin good: no scarring, atrophy or induration but moderate redness or change in pigmentation compared to adjacent skin fair: slight to moderate occurrence of scarring, atrophy or induration poor: extensive occurrence of scarring, atrophy or induration.	3 months after the last metvix PDT cycle, up to 6 months
Recurrence Rate in Complete Clearance Group	Recurrence rate in complete clearance(CC) group was analyzed.	12, 24, 36, 48 and 60 months after last Metvix PDT cycle, up to 5 years
Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT Cycle	Cosmetic outcome was assessed by both investigator and participants in participants with 100% of lesions in complete response. Overall cosmetic outcome was assessed with regard to occurrence of the following signs or symptoms; scarring, atrophy, induration, redness or change in pigmentation. The investigator graded the cosmetic outcome as: excellent: no scarring, atrophy or induration, and no or slight occurrence of redness or change in pigmentation compared lo adjacent skin good: no scarring, atrophy or induration but moderate redness or change in pigmentation compared to adjacent skin fair: slight to moderate occurrence of scarring, atrophy or induration poor: extensive occurrence of scarring, atrophy or induration.	24, 36, and 60 Months After the Last Metvix PDT Cycle, up to 5 years

Collaborators and Investigators

• Sponsor: Galderma R&D
• Investigators: Principal Investigator: Carl Vinciullo, MD, Dermatology Surgery & Laser Centre, Perth

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2000
• Primary Completion (Actual): June 1, 2006
• Study Completion (Actual): June 1, 2006

Study Registration Dates

• First Submitted: May 14, 2007
• First Submitted That Met QC Criteria: May 14, 2007
• First Posted (Estimate): May 15, 2007

Study Record Updates

• Last Update Posted (Actual): January 5, 2023
• Last Update Submitted That Met QC Criteria: April 8, 2022
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Photodynamic therapy (PDT); PDT with Metvix cream; "High risk" BCC; Basal Cell carcinoma; Histologically confirmed complete response
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Basal Cell; Carcinoma; Carcinoma, Basal Cell; Photosensitizing Agents; Dermatologic Agents; Aminolevulinic Acid; Methyl 5-aminolevulinate
• Other Study ID Numbers: PC T310/00

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No