Basal Cell Carcinoma
Conditions
Keywords
Nodular Basal Cell Carcinoma, Basal Cell Carcinoma, PDT with Metvix 160 mg/g cream, PDT with placebo cream, Histological verification
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 have 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 photoactive porphyrins levels 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 participants complete response rates based on histologically verified disappearance of the lesions at 6 months after last treatment cycle. Secondary objectives was 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 participants were randomised to PDT with Metvix cream or PDT with placebo cream. All eligible basal cell carcinoma (BCC) lesions within a participant received same treatment. All participants received two consecutive treatments one week apart. At the 3-months follow-up visit, lesions with no clinical response or progression were surgically excised. Lesions with partial response 50 percent (%) or greater reduction on lesion area) were re-treated; if they do not show complete response three months later, they were surgically excised. Lesions with complete response were surgically excised 6 months after the first or second PDT cycle. All excised tissue specimens were histologically examined.
Interventions
Sponsors
Galderma R&D
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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. * Participants with Gorlin's syndrome. * Participants with Xeroderma pigmentosum. * Participants concurrently receiving immunosuppressive medication. * Participants with a history of arsenic exposure. * Participants with BCC arising in a previous radiated area. * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Histologically Confirmed Complete Response | up to 9 months | The histological complete response was defined as 100 percent (%) of the lesions within the participant having negative findings 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 disappearence of lesion. Number of participants with histologically confirmed complete response were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Lesions With Clinically Confirmed Complete Lesion Response | up to 9 months | Clinically confirmed complete lesion response means no signs of malignant basal cells in all microscopical slides containing excised tissue. The clinically confirmed complete lesion response were reported. |
| Histological Verified Lesions With Complete Response | up to 9 months | Histological confirmed complete lesion response means no signs of malignant basal cells in all microscopical slides containing excised tissue. Number of histologically confirmed lesions with complete response were reported. |
| Clinically Verified Lesions With Complete Response | up to 9 months | Clinically confirmed complete lesion response means no signs of malignant basal cells in all microscopical slides containing excised tissue. Number of clinically confirmed lesions with complete response were reported. |
| Percentage of Lesions With Histologically Confirmed Complete Lesion Response | up to 9 months | Histological response weight means no signs of malignant basal cells in all microscopical slides containing excised tissue. The histologically confirmed complete lesion response were reported. |
| Number of Participants With Cosmetic Outcome Assessed by Investigator and Participants | up to 9 months | Cosmetic outcomes were assessed with regards to occurrence of the following signs or symptoms; scarring, atrophy, induration, redness or change in pigmentation. Cosmetic outcome were graded as excellent, good, fair or poor where: excellent: no scarring, atrophy or induration, 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 and Poor: extensive occurrence of scarring, atrophy or induration. The investigator and participants assessed the cosmetic outcome for each lesion has responded completely. Participants were asked to evaluate evaluate the cosmetic outcome according to the same categories: excellent, good, fair cosmetic outcome. Number of participants with summarized cosmetic outcomes for all symptoms as assessed by Investigator and participants were reported. |
| Number of Participants With Adverse Events and Serious Adverse Events (AEs) | up to 6 months | Adverse event (AE) was defined as any untoward medical occurrence in a participant, which does not necessarily have causal relationship with treatment. A serious AE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged in participant hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs: events between first dose of study drug that were absent before treatment/that worsened relative to pre-treatment state. TEAEs included both serious TEAEs and non-serious TEAEs. Number of participants with AEs and serious AEs were reported. |
| Number of Participants With Clinically Evaluated Complete Response | up to 9 months | The on-site investigator evaluated the lesion response by comparing to the lesion size before and after treatment. Complete response here means complete disappearance of a lesion. Number of participants for whom one or more lesions had a complete response were reported. |
Countries
United States
Participant flow
Recruitment details
A total of nine centres and one dermatopathology laboratory in United States were included. Only seven of nine centres enrolled participants. Study was conducted from first participant signed informed consent: December 2000 to Last participant last visit: April 2002
Participants by arm
| Arm | Count |
|---|---|
| Photodynamic Therapy With Metvix Cream 160 Milligrams/Gram (mg/g) Participants with BCC lesions were administered to PDT with Metvix® cream 160 mg/g applied topically for three hours, followed by illumination using noncoherent light with a fluency of 75 J/cm\*2 and fluency rate of less than 50-200 mW/cm\*2 up to 14 weeks. All participants received two consecutive treatments, one week apart thereby completing one PDT treatment cycle. | 33 |
| Photodynamic Therapy (PDT) With Placebo Cream Participants with BCC lesions were administered to PDT with Placebo cream applied topically for three hours, followed by illumination using noncoherent light with a fluency of 75 Joule per centimeter square (J/cm\*2) and fluency rate of 50-200 milliwatt per centimeter square (mW/cm\*2) up to 14 weeks. All participants received two consecutive treatments, one week apart thereby completing one PDT treatment cycle. | 32 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Photodynamic Therapy (PDT) With Placebo Cream | Total | Photodynamic Therapy With Metvix Cream 160 Milligrams/Gram (mg/g) |
|---|---|---|---|
| Age, Continuous | 67 Years | 65 Years | 62 Years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 32 Participants | 65 Participants | 33 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 7 Participants | 15 Participants | 8 Participants |
| Sex: Female, Male Male | 25 Participants | 50 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 32 |
| other Total, other adverse events | 0 / 33 | 0 / 32 |
| serious Total, serious adverse events | 1 / 33 | 5 / 32 |
Outcome results
Primary
Number of Participants With Histologically Confirmed Complete Response
The histological complete response was defined as 100 percent (%) of the lesions within the participant having negative findings 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 disappearence of lesion. Number of participants with histologically confirmed complete response were reported.
Time frame: up to 9 months
Population: Intent-to-treat (ITT) population included all participants who had BCC lesions and had received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Photodynamic Therapy (PDT) With Metvix Cream 160 Milligrams/Gram (mg/g) | Number of Participants With Histologically Confirmed Complete Response | 25 Participants |
| Photodynamic Therapy (PDT) With Placebo Cream | Number of Participants With Histologically Confirmed Complete Response | 11 Participants |
Secondary
Clinically Verified Lesions With Complete Response
Clinically confirmed complete lesion response means no signs of malignant basal cells in all microscopical slides containing excised tissue. Number of clinically confirmed lesions with complete response were reported.
Time frame: up to 9 months
Population: ITT population set included all participants who had BCC lesions and received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Photodynamic Therapy (PDT) With Metvix Cream 160 Milligrams/Gram (mg/g) | Clinically Verified Lesions With Complete Response | 28 Lesions |
| Photodynamic Therapy (PDT) With Placebo Cream | Clinically Verified Lesions With Complete Response | 0 Lesions |
Secondary
Histological Verified Lesions With Complete Response
Histological confirmed complete lesion response means no signs of malignant basal cells in all microscopical slides containing excised tissue. Number of histologically confirmed lesions with complete response were reported.
Time frame: up to 9 months
Population: ITT population set included all participants who had BCC lesions and received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Photodynamic Therapy (PDT) With Metvix Cream 160 Milligrams/Gram (mg/g) | Histological Verified Lesions With Complete Response | 32 Lesions |
| Photodynamic Therapy (PDT) With Placebo Cream | Histological Verified Lesions With Complete Response | 13 Lesions |
Secondary
Number of Participants With Adverse Events and Serious Adverse Events (AEs)
Adverse event (AE) was defined as any untoward medical occurrence in a participant, which does not necessarily have causal relationship with treatment. A serious AE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged in participant hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs: events between first dose of study drug that were absent before treatment/that worsened relative to pre-treatment state. TEAEs included both serious TEAEs and non-serious TEAEs. Number of participants with AEs and serious AEs were reported.
Time frame: up to 6 months
Population: The Safety population included all participants in the ITT who were administered at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Photodynamic Therapy (PDT) With Metvix Cream 160 Milligrams/Gram (mg/g) | Number of Participants With Adverse Events and Serious Adverse Events (AEs) | Participants With Adverse Events (AEs) | 30 Participants |
| Photodynamic Therapy (PDT) With Metvix Cream 160 Milligrams/Gram (mg/g) | Number of Participants With Adverse Events and Serious Adverse Events (AEs) | Participants With Serious Adverse Events (AEs) | 1 Participants |
| Photodynamic Therapy (PDT) With Placebo Cream | Number of Participants With Adverse Events and Serious Adverse Events (AEs) | Participants With Adverse Events (AEs) | 24 Participants |
| Photodynamic Therapy (PDT) With Placebo Cream | Number of Participants With Adverse Events and Serious Adverse Events (AEs) | Participants With Serious Adverse Events (AEs) | 5 Participants |
Secondary
Number of Participants With Clinically Evaluated Complete Response
The on-site investigator evaluated the lesion response by comparing to the lesion size before and after treatment. Complete response here means complete disappearance of a lesion. Number of participants for whom one or more lesions had a complete response were reported.
Time frame: up to 9 months
Population: ITT population set included all participants who had BCC lesions and received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Photodynamic Therapy (PDT) With Metvix Cream 160 Milligrams/Gram (mg/g) | Number of Participants With Clinically Evaluated Complete Response | 28 Participants |
| Photodynamic Therapy (PDT) With Placebo Cream | Number of Participants With Clinically Evaluated Complete Response | 15 Participants |
Secondary
Number of Participants With Cosmetic Outcome Assessed by Investigator and Participants
Cosmetic outcomes were assessed with regards to occurrence of the following signs or symptoms; scarring, atrophy, induration, redness or change in pigmentation. Cosmetic outcome were graded as excellent, good, fair or poor where: excellent: no scarring, atrophy or induration, 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 and Poor: extensive occurrence of scarring, atrophy or induration. The investigator and participants assessed the cosmetic outcome for each lesion has responded completely. Participants were asked to evaluate evaluate the cosmetic outcome according to the same categories: excellent, good, fair cosmetic outcome. Number of participants with summarized cosmetic outcomes for all symptoms as assessed by Investigator and participants were reported.
Time frame: up to 9 months
Population: ITT population set included all participants who had BCC lesions and received at least one dose of study drug. Here, Overall Number of participants analyzed signifies those participants who were evaluable for this outcome measure. Number analyzed = participantswith available data for specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Photodynamic Therapy (PDT) With Metvix Cream 160 Milligrams/Gram (mg/g) | Number of Participants With Cosmetic Outcome Assessed by Investigator and Participants | Excellent: Investigator | 17 Participants |
| Photodynamic Therapy (PDT) With Metvix Cream 160 Milligrams/Gram (mg/g) | Number of Participants With Cosmetic Outcome Assessed by Investigator and Participants | Good: Investigator | 9 Participants |
| Photodynamic Therapy (PDT) With Metvix Cream 160 Milligrams/Gram (mg/g) | Number of Participants With Cosmetic Outcome Assessed by Investigator and Participants | Fair: Investigator | 2 Participants |
| Photodynamic Therapy (PDT) With Metvix Cream 160 Milligrams/Gram (mg/g) | Number of Participants With Cosmetic Outcome Assessed by Investigator and Participants | Poor: Investigator | 0 Participants |
| Photodynamic Therapy (PDT) With Metvix Cream 160 Milligrams/Gram (mg/g) | Number of Participants With Cosmetic Outcome Assessed by Investigator and Participants | Excellent: Participant | 18 Participants |
| Photodynamic Therapy (PDT) With Metvix Cream 160 Milligrams/Gram (mg/g) | Number of Participants With Cosmetic Outcome Assessed by Investigator and Participants | Good: Participant | 8 Participants |
| Photodynamic Therapy (PDT) With Metvix Cream 160 Milligrams/Gram (mg/g) | Number of Participants With Cosmetic Outcome Assessed by Investigator and Participants | Fair: Participant | 2 Participants |
| Photodynamic Therapy (PDT) With Metvix Cream 160 Milligrams/Gram (mg/g) | Number of Participants With Cosmetic Outcome Assessed by Investigator and Participants | Poor: Participant | 0 Participants |
| Photodynamic Therapy (PDT) With Placebo Cream | Number of Participants With Cosmetic Outcome Assessed by Investigator and Participants | Poor: Participant | 0 Participants |
| Photodynamic Therapy (PDT) With Placebo Cream | Number of Participants With Cosmetic Outcome Assessed by Investigator and Participants | Excellent: Investigator | 5 Participants |
| Photodynamic Therapy (PDT) With Placebo Cream | Number of Participants With Cosmetic Outcome Assessed by Investigator and Participants | Excellent: Participant | 8 Participants |
| Photodynamic Therapy (PDT) With Placebo Cream | Number of Participants With Cosmetic Outcome Assessed by Investigator and Participants | Good: Investigator | 3 Participants |
| Photodynamic Therapy (PDT) With Placebo Cream | Number of Participants With Cosmetic Outcome Assessed by Investigator and Participants | Fair: Participant | 0 Participants |
| Photodynamic Therapy (PDT) With Placebo Cream | Number of Participants With Cosmetic Outcome Assessed by Investigator and Participants | Fair: Investigator | 1 Participants |
| Photodynamic Therapy (PDT) With Placebo Cream | Number of Participants With Cosmetic Outcome Assessed by Investigator and Participants | Good: Participant | 2 Participants |
| Photodynamic Therapy (PDT) With Placebo Cream | Number of Participants With Cosmetic Outcome Assessed by Investigator and Participants | Poor: Investigator | 0 Participants |
Secondary
Percentage of Lesions With Clinically Confirmed Complete Lesion Response
Clinically confirmed complete lesion response means no signs of malignant basal cells in all microscopical slides containing excised tissue. The clinically confirmed complete lesion response were reported.
Time frame: up to 9 months
Population: ITT population included all participants who had BCC lesions and had received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Photodynamic Therapy (PDT) With Metvix Cream 160 Milligrams/Gram (mg/g) | Percentage of Lesions With Clinically Confirmed Complete Lesion Response | 80 percentage of Lesions |
| Photodynamic Therapy (PDT) With Placebo Cream | Percentage of Lesions With Clinically Confirmed Complete Lesion Response | 51 percentage of Lesions |
Secondary
Percentage of Lesions With Histologically Confirmed Complete Lesion Response
Histological response weight means no signs of malignant basal cells in all microscopical slides containing excised tissue. The histologically confirmed complete lesion response were reported.
Time frame: up to 9 months
Population: ITT population included all participants who had BCC lesions and had received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Photodynamic Therapy (PDT) With Metvix Cream 160 Milligrams/Gram (mg/g) | Percentage of Lesions With Histologically Confirmed Complete Lesion Response | 78 percentage of lesions |
| Photodynamic Therapy (PDT) With Placebo Cream | Percentage of Lesions With Histologically Confirmed Complete Lesion Response | 33 percentage of lesions |