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

Phase 3

Completed

• Conditions: Basal Cell Carcinoma
• Interventions: Drug: Metvix® cream

• Registration Number: NCT00473343
• Lead Sponsor: Galderma R&D

Brief Summary

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.

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 Timeline

• Study Start: 2000-09
• Primary Completion: 2006-06
• Study Completion: 2006-06
• Study First Submitted: 2007-05-14
• Study First Submitted QC: 2007-05-14
• Study First Posted: 2007-05-15
• Status Verified: 2021-06
• Results First Submitted: 2022-04-08
• Results First Submitted QC: 2022-04-08
• Last Update Submitted: 2022-04-08
• Results First Posted: 2023-01-05
• Last Update Posted: 2023-01-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 102

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Metvix® PDT	Metvix® cream	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Histologically Confirmed Patient Complete Response (CR) 3 Months After Last Metvix PDT Cycle	3 months after last Metvix PDT cycle, up to 6 months	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.

Secondary Outcome Measures

Name	Time	Method
Overall Cosmetic Outcome Assessed by Participants 3 Months After the Last Metvix PDT Cycle	3 months after the last metvix PDT cycle, up to 6 months	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.
Recurrence Rate in Complete Clearance Group	12, 24, 36, 48 and 60 months after last Metvix PDT cycle, up to 5 years	Recurrence rate in complete clearance(CC) group was analyzed.
Number of Lesion With Complete Response 3 Months After Last Metvix PDT Cycle	3 months after last Metvix PDT cycle, up to 6 months	Complete response was defined as no clinically visible BCC lesions in the treatment area.
Overall Cosmetic Outcome Assessed by Investigator 3 Months After the Last Metvix PDT Cycle	3 months after the last metvix PDT cycle, up to 6 months	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.
Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT Cycle	24, 36, and 60 Months After the Last Metvix PDT Cycle, up to 5 years	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.

Trial Locations

Locations (7)

Department of Dermatology, St. George Hospital; 🇦🇺 Kogarah, New South Wales, Australia

Dermatology Department, The Queen Elisabeth Hospital; 🇦🇺 Adelaide, South Australia, Australia

Department of Dermatology, Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia

South East Dermatology, The Belmont Specialist Clinic; 🇦🇺 Carnia, Queensland, Australia

Clinic B, Repatriation Campus, Austin & Repatriation Medical Centre; 🇦🇺 Heidelberg, Victoria, Australia

Dermatology Surgery & Laser Centre, The Perth Surgicentre; 🇦🇺 Perth, Western Australia, Australia

Fremantle Dermatology; 🇦🇺 Fremantle, Western Australia, Australia