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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Nantes University Hospital
Sponsor:
Collaborator:
MEDA Pharma GmbH & Co. KG
Information provided by (Responsible Party):
Nantes University Hospital
ClinicalTrials.gov Identifier:
NCT01720407
First received: October 23, 2012
Last updated: September 18, 2014
Last verified: September 2014
  Purpose

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 vehicle 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.


Condition Intervention Phase
Lentigo Maligna Melanoma (Head or Neck)
Drug: Imiquimod cream + surgery
Drug: vehicle + surgery
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Nantes University Hospital:

Primary Outcome Measures:
  • 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. [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The number of surgical re-excisions required to obtain complete remission. [ Time Frame: Baseline, 2 months till 3 years ] [ Designated as safety issue: No ]
  • The number of recurrences, defined as the reappearance of pigmentation within 3 years of surgical excision. [ Time Frame: Baseline, 2 months till 3 years ] [ Designated as safety issue: No ]
  • The number of histologically confirmed complete remissions under imiquimod. [ Time Frame: Baseline, 2 months till 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 268
Study Start Date: December 2012
Estimated Study Completion Date: August 2019
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Imiquimod Drug: Imiquimod cream + surgery
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).
Placebo Comparator: Placebo Drug: vehicle + surgery
vehicle (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).

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01720407

Contacts
Contact: Amir Khammari 02 53 48 32 80 amir.khammari@chu-nantes.fr

Locations
France
CHU Recruiting
Besançon, France
Principal Investigator: François AUBIN         
CHU Hôpital Saint André Recruiting
Bordeaux, France
Principal Investigator: Caroline DUTRIAUX         
CHU Recruiting
Bordeaux, France
Principal Investigator: Marie BEYLOT-BARRY         
AP-HP Hôpital Ambroise Paré Recruiting
Boulogne Billancourt, France
Principal Investigator: Philippe SAIAG         
CHU Recruiting
Brest, France
Principal Investigator: Laurent MISERY         
CHRU Recruiting
Caen, France
Principal Investigator: Anne DOMPMARTIN         
CHU Michallon Recruiting
Grenoble, France
Principal Investigator: Marie-Thérèse LECCIA         
CH Recruiting
Le Mans, France
Principal Investigator: Hervé MAILLARD         
CHRU Recruiting
Lille, France
Principal Investigator: Laurent MORTIER         
CHU Recruiting
Limoges, France
Principal Investigator: Christophe BEDANE         
CHU Recruiting
Lyon sud, France
Principal Investigator: Luc THOMAS         
AP-HM Recruiting
Marseille, France
Principal Investigator: Jean-Jacques GROB         
CHU Recruiting
Montpellier, France
Principal Investigator: Bernard GUILLOT         
Centre Hospitalier Universitaire de Nantes Recruiting
Nantes, France, 44000
Principal Investigator: Brigitte Dréno, MD, PhD         
CHU Recruiting
Nice, France
Principal Investigator: Jean-Philippe LACOUR         
CHU Recruiting
Orléans, France
Principal Investigator: Guido BENS         
AP-HP Hôpital Saint Louis Recruiting
Paris, France
Principal Investigator: Celeste LEBBE         
CHU Milétrie Recruiting
Poitiers, France
Principal Investigator: Ewa WIERZBICKA-HAINAUT         
CHU Recruiting
Reims, France
Principal Investigator: Florent GRANGE         
CHU Pontchaillou Recruiting
Rennes, France
Principal Investigator: Alain DUPUY         
CHU Recruiting
Saint-Etienne, France
Principal Investigator: Frédéric CAMBAZARD         
CHU Hôpital Larrey Recruiting
Toulouse, France
Principal Investigator: Nicolas MEYER         
CHU Recruiting
Tours, France
Principal Investigator: Laurent MACHET         
Sponsors and Collaborators
Nantes University Hospital
MEDA Pharma GmbH & Co. KG
Investigators
Principal Investigator: Brigitte Dréno, MD, PhD Nantes University Hospital
  More Information

No publications provided

Responsible Party: Nantes University Hospital
ClinicalTrials.gov Identifier: NCT01720407     History of Changes
Other Study ID Numbers: BRD11/06-S
Study First Received: October 23, 2012
Last Updated: September 18, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Nantes University Hospital:
Dermatology/ Skin cancers/Lentigo maligna melanoma

Additional relevant MeSH terms:
Pigmentation Disorders
Hutchinson's Melanotic Freckle
Lentigo
Melanoma
Hyperpigmentation
Melanosis
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Skin Diseases
Imiquimod
Adjuvants, Immunologic
Antineoplastic Agents
Immunologic Factors
Interferon Inducers
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014