Basal Cell Carcinoma
Conditions
Keywords
Photodynamic therapy (PDT), PDT with Metvix cream, High risk BCC, Basal Cell carcinoma, Histologically confirmed complete response
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).
Interventions
DRUGMetvix® cream
Sponsors
Galderma R&D
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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. |
Countries
Australia
Participant flow
Recruitment details
A total of 102 participants were randomized at seven different center in Australia.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 102 |
| Total | 102 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 9 |
| Overall Study | Lost to Follow-up | 8 |
| Overall Study | Other un-specified reason | 3 |
| Overall Study | Treatment failure | 27 |
| Overall Study | Withdrew consent | 3 |
Baseline characteristics
| Characteristic | Metvix® PDT |
|---|---|
| Age, Continuous | 64 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 102 Participants |
| Sex: Female, Male Female | 36 Participants |
| Sex: Female, Male Male | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 7 / 102 |
| other Total, other adverse events | 88 / 102 |
| serious Total, serious adverse events | 10 / 102 |
Outcome results
Primary
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.
Time frame: 3 months after last Metvix PDT cycle, up to 6 months
Population: Intent-to-treat analysis set included all the participants enrolled in the study who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Metvix® PDT | Percentage of Participants With Histologically Confirmed Patient Complete Response (CR) 3 Months After Last Metvix PDT Cycle | 80 percentage of participants |
Secondary
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.
Time frame: 3 months after last Metvix PDT cycle, up to 6 months
Population: Intent-to-treat analysis set included all the participants enrolled in the study who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Metvix® PDT | Number of Lesion With Complete Response 3 Months After Last Metvix PDT Cycle | 141 lesions |
Secondary
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.
Time frame: 24, 36, and 60 Months After the Last Metvix PDT Cycle, up to 5 years
Population: Intent-to-treat analysis set included all the participants enrolled in the study who received at least one dose of study treatment. Here overall Number of participants analyzed signifies those participants who were evaluable for this outcome measure. Number analyzed, signifies those participants who were evaluable for this outcome measure at the specified time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT Cycle | Excellent: At 24 month | 34 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT Cycle | Good: At 24 month | 15 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT Cycle | Fair: At 24 month | 7 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT Cycle | Poor: At 24 month | 1 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT Cycle | Excellent: At 36 month | 31 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT Cycle | Good: At 36 month | 13 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT Cycle | Fair: At 36 month | 6 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT Cycle | Excellent: At 60 month | 35 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT Cycle | Good: At 60 month | 7 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT Cycle | Fair: At 60 month | 1 Participants |
Secondary
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.
Time frame: 3 months after the last metvix PDT cycle, up to 6 months
Population: Intent-to-treat analysis set included all the participants enrolled in the study who received at least one dose of study treatment. Here overall Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 3 Months After the Last Metvix PDT Cycle | Investigator: Excellent | 37 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 3 Months After the Last Metvix PDT Cycle | Investigator: Good | 16 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 3 Months After the Last Metvix PDT Cycle | Investigator: Fair | 28 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 3 Months After the Last Metvix PDT Cycle | Investigator: Not applicable | 1 Participants |
Secondary
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.
Time frame: 3 months after the last metvix PDT cycle, up to 6 months
Population: Intent-to-treat analysis set included all the participants enrolled in the study who received at least one dose of study treatment. Here overall Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Participants 3 Months After the Last Metvix PDT Cycle | Participants: Excellent | 40 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Participants 3 Months After the Last Metvix PDT Cycle | Participants: Good | 39 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Participants 3 Months After the Last Metvix PDT Cycle | Participants: Fair | 2 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Participants 3 Months After the Last Metvix PDT Cycle | Participants: Not applicable | 0 Participants |
Secondary
Recurrence Rate in Complete Clearance Group
Recurrence rate in complete clearance(CC) group was analyzed.
Time frame: 12, 24, 36, 48 and 60 months after last Metvix PDT cycle, up to 5 years
Population: Intent-to-treat analysis set included all the participants enrolled in the study who received at least one dose of study treatment. Here overall Number of participants analyzed signifies those participants who were evaluable for this outcome measure. Number analyzed, signifies those participants who were evaluable for this outcome measure at the specified time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Metvix® PDT | Recurrence Rate in Complete Clearance Group | 12 months | 8 Participants |
| Metvix® PDT | Recurrence Rate in Complete Clearance Group | 48 months | 21 Participants |
| Metvix® PDT | Recurrence Rate in Complete Clearance Group | 24 months | 16 Participants |
| Metvix® PDT | Recurrence Rate in Complete Clearance Group | 36 months | 20 Participants |
| Metvix® PDT | Recurrence Rate in Complete Clearance Group | 60 months | 23 Participants |