Clinical Trial: Prospective Study of Ingenol Mebutate for Non-invasive Lentigo Melanoma of the Face

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Prospective Study of Ingenol Mebutate for Non-invasive Lentigo Melanoma of the Face - Study PICAMEL

Brief 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).


Detailed Summary:

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
Sponsor: Centre Hospitalier Universitaire de Nice

Current Primary Outcome: the clinical and histological complete response (CR) of non-invasive LM 2 months after the end of a treatment cycle. In case of failure of the first cycle, a second will be realized and the CR will be re-assessed at 4.5 months [ Time Frame: at 2 months after end of treatment ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • disease-free survival [ Time Frame: maximum of 36 months ]
    calculated from the date of the CR and the date of relapse or death related to the non-invasive LM (very unlikely here). Relapse is defined as the clinical appearance of a new pigmented lesion with histopathological analysis, from one or more biopsy (s), which confirms the diagnosis of non-invasive LM.
  • side effects [ Time Frame: at 36 months ]
    • The type, frequency, severity and the time to onset of side effects will be reported. The side effects will be classified into grades according to WHO criteria and also using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The intensity of short-term local side effects will be evaluated by the Local Skin Reaction score
  • specific diagnostic signs of treatment failure [ Time Frame: maximun of 36 months ]
  • relapse of non-invasive LM [ Time Frame: maximum of 36 months ]


Original Secondary Outcome: Same as current

Information By: Centre Hospitalier Universitaire de Nice

Dates:
Date Received: March 15, 2016
Date Started: June 2016
Date Completion: November 2020
Last Updated: July 25, 2016
Last Verified: March 2016