Clinical trial NCT01720407: Relevance of Imiquimod as Neo-adjuvant Treatment to Reduce Excision Size and the Risk of Intralesional Excision in Lentigo Malignant of the Face
Official title: Relevance of Imiquimod as Neo-adjuvant Treatment to Reduce Excision Size and the Risk of Intralesional Excision in Lentigo Malignant of the Face
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lentigo Maligna Melanoma (Head or Neck)
Keywords: Dermatology/ Skin cancers/Lentigo maligna melanoma
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
Collaborators: name: MEDA Pharma GmbH & Co. KG
First posted: 2012-11-02
Enrollment: 259
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Lentigo malignant (LM) is an intraepidermal melanocytic proliferation occurring on photoexposed skin. In our project, this term applies both to Dubreuilh's melanosis and to Dubreuilh's intraepidermal melanoma. It consequently excludes invasive melanoma. Although surgery is the treatment of choice, it remains without consensus on the margins (5 mm or 10 mm) excision for a localized tumor on the face.

Several studies have shown that imiquimod, activating local immunity by interferon production, induced LM or MLM regression and could also decrease the frequency of relapses.

The principal aim of our project is to study the effect of imiquimod versus placebo in pre-operative neoadjuvant treatment aimed at reducing both surgical margins, as from the first surgical procedure, and the frequency of short and medium term recurrence of LM. Furthermore, the improvement in patient quality of life could also be significant.

Detailed description: The primary endpoint of the study is to demonstrate that neoadjuvant treatment of LM by imiquimod prior to surgery can reduce the frequency of intralesional excisions as from the first surgical procedure, with a healthy tissue margin of 5mm. Furthermore, the improvement in patient quality of life could also be significant.

The number of patients to be included in the study is 268.

For each patient, the study will involve several stages (S), as follows:

S0 (Selection): information and obtaining of the patient's informed consent. Performance of biopsy for histological confirmation of LM

S1 (S0 + \~ 2 weeks): patient inclusion following anatomopathological confirmation of LM. Patient randomisation in one or other study arm: imiquimod versus placebo and initiation of topical treatment.

S2 (S1 + 4 weeks): Discontinuation of imiquimod/placebo application. Scheduling of the surgical procedure 4 weeks later.

S3 (S2 + 4 weeks): Surgery.

S4: After the last surgical procedure, simple clinical follow up will be ensured every 6 months for a period of 3 years, in order to study the recurrence rate.

Eligibility criteria: Inclusion Criteria:

* Patients from both sexes aged over 18 years and operable
* Presenting with LM of the face, the neck, or the scalp (in case of hairless scalp only) histologically confirmed by biopsy
* Patients presenting with a primitive lesion, of a surface ≥ to 1cm² and ≤ to 20cm², with the possibility of graft or flap reconstruction
* LM previously untreated by surgery
* LM without prior treatment with liquid nitrogen or any other local treatment within 3 months
* ECOG ≤ 2
* Leucocytes ≥ 3,000/mm³
* Neutrophil count ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Haemoglobin ≥ 9.0g/dL
* Absence of severe evolutive infection
* Absence of known HIV infection
* Absence of corticotherapy and treatment by immunosuppressive agents
* Absence of excoriation and scarring biopsy prior to application of study treatment
* Membership to a social security insurance scheme.
* Negative pregnancy test conducted during the inclusion consultation for non-menopausal women.
* Effective contraception for patients of childbearing age
* Signed informed consent

Exclusion Criteria:

* LM located on the eyelids are excluded, together with LM in anatomic sites other than the face, the neck or the scalp
* Melanomas other than LM
* Invasive LM
* LM with a surface area \< to 1cm² or \> to 20cm²
* LM of which the macroscopic contours cannot be defined
* Patients who are allergic to imiquimod excipient (eg hydroxybenzoate)
* Patients with a hypersensitivity to active substances or to any of the excipients of the placebo (for example propyl parahydroxybenzoate)
* Patients treated by immunosuppressive agents, immunomodulators, cytotoxic agents or corticosteroids (local and systemic) during the 4-week period prior to the selection visit
* Patients with auto-immune disease (except vitiligo) or transplant patients
* Cutaneous reconstruction not possible
* Presence of associated evolutive neoplasia since less than 5 years (with the exception of basal cell carcinoma, Bowen's carcinoma and carcinoma in situ of the cervix)
* Patient refusing surgery under local or general anaesthesia
* Pregnant women

Primary outcomes:
measure: The primary endpoint is the margin of resection. Success is defined by an extralesional excision as from the first surgical procedure performed with a healthy tissue margin of 5 mm.
timeFrame: 10 weeks
Secondary outcomes:
measure: The number of surgical re-excisions required to obtain complete remission.
timeFrame: Baseline, 2 months till 3 years
measure: The number of recurrences, defined as the reappearance of pigmentation within 3 years of surgical excision.
timeFrame: Baseline, 2 months till 3 years
measure: The number of histologically confirmed complete remissions under imiquimod.
timeFrame: Baseline, 2 months till 3 years
Other outcomes:
Locations:
city: Besançon
country: France
facility: CHU
city: Bordeaux
country: France
facility: CHU Hôpital Haut-Lévêque
city: Bordeaux
country: France
facility: CHU Hôpital Saint André
city: Boulogne Billancourt
country: France
facility: AP-HP Hôpital Ambroise Paré
city: Brest
country: France
facility: CHU
city: Grenoble
country: France
facility: CHU Michallon
city: Le Mans
country: France
facility: CH
city: Lille
country: France
facility: CHRU
city: Limoges
country: France
facility: CHU
city: Lyon
country: France
facility: CHU
city: Marseille
country: France
facility: AP-HM
city: Montpellier
country: France
facility: CHU
city: Nantes
country: France
facility: Centre Hospitalier Universitaire de Nantes
city: Nice
country: France
facility: CHU
city: Orléans
country: France
facility: CHU
city: Paris
country: France
facility: AP-HP Hôpital Saint Louis
city: Poitiers
country: France
facility: CHU Milétrie
city: Reims
country: France
facility: CHU
city: Rennes
country: France
facility: CHU Pontchaillou
city: Saint-Etienne
country: France
facility: CHU
city: Toulouse
country: France
facility: Chu (Iucto)
city: Tours
country: France
facility: CHU
Study officials:
affiliation: Nantes University Hospital
name: Brigitte Dréno, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: