Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02723721 |
| Other study ID # |
15-PP-14 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
June 15, 2016 |
| Est. completion date |
January 27, 2020 |
Study information
| Verified date |
November 2020 |
| Source |
Centre Hospitalier Universitaire de Nice |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Non-invasive lentigo maligna (LM) is characterized by an in situ proliferation of melanoma
cells, limited to the epidermis. It is found most commonly on the head and neck of elderly
persons, with a peak incidence in the seventh or eighth decade. If untreated, it may develop
into invasive melanoma. The gold standard treatment for LM is surgery using a 5-10 mm margin.
However, the lesions can be large, and conventional surgery can be difficult, particularly on
the face.
Then, there is a need for a topical non-surgical treatment of LM. Ingenol mebutate
(IM)/Picato® is able to induce cell apoptosis and an inflammatory reaction in the epidermis
and superficial dermis.
Thus, the investigators hypothesize that the topical use of Picato® could induce the cure or
a prolonged remission of non-invasive LM.
Because of the exploratory phase of this study (no case report and no clinical trial at the
early phase of designing this study, only one case report at the time of submission of this
form) the investigators will conduct an open label study limited to patients who are not
eligible to, or who refuse surgical treatment of their LM.
The main objective of this study is to determine the proportion of patients with complete
response (CR) obtained 2 months after one or two cycles (for patients who did not respond to
the first cycle) of topical treatment by IM 150 µg/g for non-invasive LM of the face (head
and neck).
Description:
Lentigo maligna (LM) is a form of malignant melanoma in situ seen predominantly on
chronically sun-damaged skin. It is found most commonly on the head and neck of elderly
persons, with a peak incidence in the seventh or eighth decade. If untreated, it may develop
into invasive melanoma. The gold standard treatment for LM is surgery using a 5-10 mm margin.
However, the lesions can be large, and conventional surgery can be difficult, particularly on
the face. Furthermore, the extent of LM tends to be underestimated because the exact limits
of the lesion are not always easy to determine. Thus, relapses and repeated surgical
procedures are common. Moreover, LM appears in elderly people who often have anaesthetic
contraindications. When surgery is not or no more feasible, superficial radiotherapy or
destructive treatment by topical immunotherapy using imiquimod 5% cream may be used, but the
efficacy of these treatments remains to be clearly defined. Regarding the use of imiquimod it
has been reported in about 15 isolated cases and in 7 open studies (most of them prospective)
for a total of 189 patients. The modalities of use were variable but most of the time once a
day, 5 days per week for 3 months. The response rate varied from 53 % to 100%. The major
limitations to the use of imiquimod are: 1- a possible lower rate of remission than surgery;
2- the observance of a topical irritating treatment for an extended period.
Thus, there is a need for a topical non-surgical treatment of LM.
Picato® is a topical gel for cutaneous application that contains the active substance ingenol
mebutate, which is obtained from the aerial parts of the plant species Euphorbia peplus. by
extraction and purification. It is indicated for the cutaneous treatment of
non-hyperkeratotic, non-hypertrophic actinic keratosis in adults. The mechanism of action of
ingenol mebutate in actinic keratosis is not fully understood. In vivo and in vitro models
have shown a dual mechanism of action: 1) induction of local lesion cell death and 2)
promotion of an inflammatory response characterised by infiltration of immunocompetent cells.
In addition to this effect on actinic keratoses, a recent study has shown that treatment of
superficial basal cell carcinomas with ingenol mebutate gel 500 µg/g under occlusion with an
aluminum disk, was efficacious, even when applied only for one day. On the contrary, the same
treatment for up to 3 consecutive days showed less clinical benefit in seborrheic keratoses,
suggesting a selectivity or penetration variations of ingenol mebutate for cancer cells vs
benign cells.
In vitro, it has been shown that ingenol mebutate is able to kill melanoma cells mainly by
induction of apoptosis which seems to be secondary to the activation of Protein Kinase C.
Based on these data and on previous studies with imiquimod, the investigators suggest that
ingenol mebutate might have a clinical effect on melanoma, particularly for superficial
intraepidermal lesions of LM. Because these lesions are mostly localised on the face, the
concentration of 150 µg/g should be tested first to avoid local skin secondary effects.
The investigators hypothesize that the topical use of Picato® will induce the cure or a
prolonged remission of non-invasive LM in patients that are not eligible to or refuse
surgery.
The main objective of this study is to determine the proportion of patients with complete
response (CR) obtained 2 months after one or two cycles (for patients who did not respond to
the first cycle) of topical treatment by IM 150 µg/g for non-invasive LM of the face (head
and neck).
The secondary objectives are:
1. To assess the disease-free survival after 1 or 2 cycles of IM 150μg / g. for
non-invasive LM,
2. To determine the safety of treatment,
3. To evaluate the diagnostic performance of in vivo reflectance confocal microscopy (RCM)
and High Definition Optical Coherence Tomography (HD-OCT) for diagnosis of treatment
failure and relapse of LM compared to the standard represented by pathological
examination, in monitoring of treatment response and relapse.
The patients will be included after providing informed consent if they have a biopsy-proven
non-invasive LM on the head (face or scalp) and if they are not eligible to, or if they
refuse surgical treatment.
They will apply on and 1 cm around the lesion, 0.47 g of Picato® gel 150 µg/g, once a day on
3 consecutive days.
The short term efficacy will be evaluated at 2 months, clinically (with Wood's lamp and
dermoscopic examination) and histopathologically.
For patients being cured at 2 months, the long term efficacy will be evaluated every 6 months
for 36 months, using the same criteria.
For patients having no or only partial remission at 2 months, the treatment will be applied
using the same protocol (0.47 g of Picato® gel 150 µg/g, once a day on 3 consecutive days on
and 1 cm around the lesion). They will be evaluated 2 months after the retreatment and then
every 6 months for 36 months. The safety and local side effects will be evaluated at each
visit.
For centers equipped with in vivo reflectance confocal microscopy (RCM) and high-definition
optical coherence tomography (HD-OCT), patients will have imaging of the lesion with these
techniques before and after treatment.
