Relevance of Imiquimod as Neo-adjuvant Treatment to Reduce Excision Size and the Risk of Intralesional Excision in Lentigo Malignant of the Face (ImiReduc)

Nantes University Hospital (NUH)

Status and phase

Completed

Phase 3

Conditions

Lentigo Maligna Melanoma (Head or Neck)

Treatments

Drug: Placebo + surgery

Drug: Imiquimod cream + surgery

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01720407

BRD/11/06-S

Details and patient eligibility

About

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.

Full 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.

Enrollment

259 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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