PDT With Metvix 160 mg/g Cream Versus PDT With Placebo Cream in Participants With Primary Nodular Basal Call Carcinoma

Phase 3

Completed

Conditions: Basal Cell Carcinoma

Interventions: Drug: Placebo
Drug: PDT with Metvix 160 mg/g cream

Registration Number: NCT00472043

Lead Sponsor: Galderma R&D

Brief Summary: Photodynamic therapy (PDT) was the selective destruction of abnormal cells through light activation of a photosensitiser in the presence of oxygen. These cells accumulated more photosensitiser than normal cells. The photosensitiser generated reactive oxygen species upon illumination.

For skin diseases, there had been an increasing interest in using precursors of the endogenous photosensitiser protoporphyrin IX (PpIX). The most commonly used precursors had been 5-aminolevulinic acid (ALA) and its derivatives. The present test drug, Metvix®, contained the methyl ester of ALA, which penetrated the lesions well and shows high lesion selectivity .

In vitro studies of animal and human tissues had shown significant intracellular formation of photoactive porphyrins after addition of Metvix®. The increased levels of photoactive porphyrins induced cytotoxic effects in tumour cells after photoactivation.

The primary objective was to compare PDT with Metvix® cream to PDT with placebo cream in terms of participant complete response rates based on histologically verified disappearance of the lesions at 6 months after last treatment cycle.

Secondary objectives were to compare the two treatments in terms of histological and clinical mean participant response weighted by the number of lesions within a participant, lesion response rates across participants, clinical complete participant response, cosmetic outcome and adverse events.

Detailed Description: A participant was randomised to PDT with Metvix® cream or PDT with placebo cream. All eligible Basal cell carcinoma (BCC) lesions within a participant had got the same treatment. All participants got two consecutive treatments one week apart. At the 3-months follow-up visit, lesions with no clinical response or progression had been surgically excised. Lesions with partial response (50% or greater reduction on lesion area) had been re-treated, if they do not show complete response three months later they would have been be surgically excised. Lesions with complete response had been surgically excised 6 months after the first or second PDT cycle. All excised tissue specimens had been histologically examined.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 66

Inclusion Criteria

A participant with primary, nodular BCC lesion(s) suitable for entry is defined as a participant with

Clinically diagnosed primary nodular BCC lesion(s).
Histologically confirmed diagnosis of BCC.
BCC lesions suitable for simple excision surgery.
Males or females above 18 years of age.
Written informed consent.

Exclusion Criteria

A participant that is ineligible for inclusion is a participant fulfilling any of the following criteria:

Participants with porphyria.
Participant with Gorlin's syndrome.
Participant with Xeroderma pigmentosum.
Participants concurrently receiving immunosuppressive medication.
Participants 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 must use adequate contraception (e.g. barrier methods, oral contraceptives or intrauterine device) during the treatment period and one month thereafter. In addition, they must have a negative pregnancy test prior to treatment.
Conditions associated with a risk of poor protocol compliance.

Lesion Exclusion Criteria:

A nodular BCC lesion in periorbital area, ears and nasolabial fold.
A nodular BCC lesion with the longest diameter less than 6 mm or larger than 15 mm in face/scalp, larger than 20 mm on extremities and neck and larger than 30 mm on truncus.
Pigmented nodular BCC lesion(s).
Morpheaform nodular BCC lesion(s).
Infiltrating nodular BCC lesion(s).
Prior treatment of the BCC lesion(s).

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants with primary nodular basal cell carcinoma received Metvix® matching placebo cream. A thick layer of study cream was applied directly on the lesion and on 5 mm of the surrounding tissue. An approximately 1 mm thick layer of cream was applied to cover the lesion completely. The study cream was applied for at least 3 hours followed by illumination using non-coherent red (570-670 nm) light at a fluence of 50- 75 J/cm\^2.
Metvix® cream 160 milligram per gram	PDT with Metvix 160 mg/g cream	Methyl aminolevulinate hydrochloride 160 milligram (mg)/gram (g) cream were received by participants with primary nodular basal cell carcinoma. A thick layer of study cream was applied directly on the lesion and on 5 mm of the surrounding tissue. An approximately 1 mm thick layer of cream was applied to cover the lesion completely. The study cream was applied for at least 3 hours followed by illumination using non-coherent red (570-670 nm) light at a fluence of 50- 75 J/cm\^2.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Histologically Confirmed Complete Response (CR)	up to 6 months	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. Histological examination included evaluation of all the microscopical slides from the excised tissue for presence of malignant basal cells. Complete response was defined as complete disappearance of lesion. Percentage of participants with histologically confirmed complete response were reported.

Secondary Outcome Measures

Name	Time	Method
Histological Lesion Response	Up to 3 months	Histological examination included from the excised tissue were examined for presence of malignant basal cells, where complete response (CR) was no signs of malignant basal cells and non-CR was evidence of malignant basal cells
Percentage of Lesions Per Participant: Histologically Confirmed Participant Weighted Response	Up to 3 months	Histological response weight means no signs of malignant basal cells in all microscopical slides containing excised tissue. The histologically confirmed participant weighted response, weighted by percentage of lesions per participant are reported in this outcome measure. Number of lesions per participant with-in treatment group were calculated in following way: ni = number of lesions within 1 participant, ci= number of lesions in complete response within 1 participant, xi= 100%. ci/ni= response rate within one participant, Nt= number of participant within one treatment, nt=number of lesions with-in one treatment, wi=ni/nt= weight for one participant with Nt Σ wi (i=1) = 1 for each treatment.
Cosmetic Outcomes for Lesions Assessed by Investigator	Up to 3 months	Cosmetic outcome for those lesions with complete histological response was assessed by both the investigator and by the participant. Cosmetic outcome was assessed with regards to occurrence of the following signs or symptoms like scarring, atrophy, induration, redness, and change in pigmentation. The cosmetic outcome was graded as excellent: no scarring, atrophy or induration, and no or slight occurrence of redness or change in pigmentation compared to 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.
Percentage of Participants With Clinically Confirmed Participant Complete Response (CR)	Up to 9 months	A CR to treatment was documented clinically by visual evaluation and palpation. The on-site investigator evaluated the lesion response by comparing with the lesion size before treatment using the following definitions: CR - complete disappearance of a lesion. Partial response (PR) -the longest diameter of the lesion is reduced by 50% or more. No response (NR) - the longest diameter of the lesion is less than 50% reduced. Progression - the longest diameter is increased by 20% or more.
Cosmetic Outcomes for Lesions Assessed by Participants	Up to 3 months	Cosmetic outcome for those lesions with complete histological response was assessed by both the investigator and by the participant. Cosmetic outcome was assessed with regards to occurrence of the following signs or symptoms like scarring, atrophy, induration, redness, and change in pigmentation. The cosmetic outcome was graded as excellent: no scarring, atrophy or induration, and no or slight occurrence of redness or change in pigmentation compared to 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.
Number of Participants With Serious Adverse Events (SAEs) and AEs Leading to Discontinuation	Up to 6 months	An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily had a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A SAE was any untoward medical occurrence that at any dose: results in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect.

Trial Locations

Locations (7): Department of Dermatology, St. Vincent's Hospital Melbourne
🇦🇺
Fitzroy, Victoria, Australia
Fremantle Dermatology
🇦🇺
Fremantle, Western Australia, Australia
Dept. of Dermatology, Royal Prince Alfred Hospital
🇦🇺
Camperdown, New South Wales, Australia
Dr. Michael Freeman
🇦🇺
Benowa, Queensland, Australia
Dermatology Dept., Princess Alexandra Hospital
🇦🇺
Woolloongabba, Queensland, Australia
Dermatology Dept., St. George Hospital
🇦🇺
Kogarah, New South Wales, Australia
Dermatology Centre
🇦🇺
Liverpool, New South Wales, Australia