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

NCT01720407 | Completed Phase 3

• 1 other identifier: BRD/11/06-S
• Study Type: interventional
• Target: 259
• Locations: 1 country
• Sites: 22

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.

Conditions

Lentigo Maligna Melanoma (Head or Neck)

Keywords

Dermatology/ Skin cancers/Lentigo maligna melanoma

Outcome Measures

Primary Outcomes (1)

• 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.

  10 weeks

Secondary Outcomes (3)

• The number of surgical re-excisions required to obtain complete remission.

  Baseline, 2 months till 3 years

• The number of recurrences, defined as the reappearance of pigmentation within 3 years of surgical excision.

  Baseline, 2 months till 3 years

• The number of histologically confirmed complete remissions under imiquimod.

  Baseline, 2 months till 3 years

Study Arms (2)

Imiquimod

EXPERIMENTAL

Drug: Imiquimod cream + surgery

Placebo

PLACEBO COMPARATOR

Drug: Placebo + surgery

Interventions

Imiquimod cream + surgery DRUG

Imiquimod (5 times per week) applied to and extending 1cm beyond the lesion for a period of 4 weeks (i.e. a total of 20 applications), followed by surgery performed four weeks after the last application of the topical treatment. If excision is intralesional, re-excision at 5mm will be performed within a few days (equivalent to 2-stage surgery).

Imiquimod

Placebo + surgery DRUG

Placebo (5 times per week) applied to and extending 1cm beyond the lesion for a period of 4 weeks, followed by surgery performed four weeks after the last application of the topical treatment. If excision is intralesional, re-excision of 5mm of clinically healthy tissue will be performed within a few days (equivalent to 2-stage surgery).

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Nantes University Hospital: lead
• MEDA Pharma GmbH & Co. KG: collaborator

Study Sites (22)

CHU

Besançon, France

Location

CHU Hôpital Haut-Lévêque

Bordeaux, France

Location

CHU Hôpital Saint André

Bordeaux, France

Location

AP-HP Hôpital Ambroise Paré

Boulogne-Billancourt, France

Location

CHU

Brest, France

Location

CHU Michallon

Grenoble, France

Location

CH

Le Mans, France

Location

CHRU

Lille, France

Location

CHU

Limoges, France

Location

CHU

Lyon, France

Location

AP-HM

Marseille, France

Location

CHU

Montpellier, France

Location

Centre Hospitalier Universitaire de Nantes

Nantes, 44000, France

Location

CHU

Nice, France

Location

CHU

Orléans, France

Location

AP-HP Hôpital Saint Louis

Paris, France

Location

CHU Milétrie

Poitiers, France

Location

CHU

Reims, France

Location

CHU Pontchaillou

Rennes, France

Location

CHU

Saint-Etienne, France

Location

Chu (Iucto)

Toulouse, France

Location

CHU

Tours, France

Location

Related Publications (1)

• Gorry C, McCullagh L, O'Donnell H, Barrett S, Schmitz S, Barry M, Curtin K, Beausang E, Barry R, Coyne I. Neoadjuvant treatment for stage III and IV cutaneous melanoma. Cochrane Database Syst Rev. 2023 Jan 17;1(1):CD012974. doi: 10.1002/14651858.CD012974.pub2.

  PMID: 36648215 DERIVED

MeSH Terms

Interventions

Surgical Procedures, Operative

Study Officials

• Brigitte Dréno, MD, PhD

  Nantes University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Surgeon does not know the result of randomization.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2012
• First Posted: November 2, 2012
• Study Start: December 1, 2012
• Primary Completion: October 1, 2019
• Study Completion: November 10, 2022
• Last Updated: December 6, 2022

Record last verified: 2022-12

Locations

FR (22)