Relevance of Imiquimod as Neo-adjuvant Treatment to Reduce Excision Size and the Risk of Intralesional Excision in Lentigo Malignant of the Face (ImiReduc)
Primary Purpose
Lentigo Maligna Melanoma (Head or Neck)
Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Imiquimod cream + surgery
Placebo + surgery
Sponsored by
About this trial
This is an interventional treatment trial for Lentigo Maligna Melanoma (Head or Neck) focused on measuring Dermatology/ Skin cancers/Lentigo maligna melanoma
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
Sites / Locations
- CHU
- CHU Hôpital Haut-Lévêque
- CHU Hôpital Saint André
- AP-HP Hôpital Ambroise Paré
- CHU
- CHU Michallon
- CH
- CHRU
- CHU
- CHU
- AP-HM
- CHU
- Centre Hospitalier Universitaire de Nantes
- CHU
- CHU
- AP-HP Hôpital Saint Louis
- CHU Milétrie
- CHU
- CHU Pontchaillou
- CHU
- Chu (Iucto)
- CHU
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Imiquimod
Placebo
Arm Description
Outcomes
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.
Secondary Outcome Measures
The number of surgical re-excisions required to obtain complete remission.
The number of recurrences, defined as the reappearance of pigmentation within 3 years of surgical excision.
The number of histologically confirmed complete remissions under imiquimod.
Full Information
NCT ID
NCT01720407
First Posted
October 23, 2012
Last Updated
December 5, 2022
Sponsor
Nantes University Hospital
Collaborators
MEDA Pharma GmbH & Co. KG
1. Study Identification
Unique Protocol Identification Number
NCT01720407
Brief Title
Relevance of Imiquimod as Neo-adjuvant Treatment to Reduce Excision Size and the Risk of Intralesional Excision in Lentigo Malignant of the Face
Acronym
ImiReduc
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
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
December 2012 (Actual)
Primary Completion Date
October 2019 (Actual)
Study Completion Date
November 10, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nantes University Hospital
Collaborators
MEDA Pharma GmbH & Co. KG
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lentigo Maligna Melanoma (Head or Neck)
Keywords
Dermatology/ Skin cancers/Lentigo maligna melanoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Masking Description
Surgeon does not know the result of randomization.
Allocation
Randomized
Enrollment
259 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Imiquimod
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Imiquimod cream + surgery
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Placebo + surgery
Intervention Description
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).
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
The number of surgical re-excisions required to obtain complete remission.
Time Frame
Baseline, 2 months till 3 years
Title
The number of recurrences, defined as the reappearance of pigmentation within 3 years of surgical excision.
Time Frame
Baseline, 2 months till 3 years
Title
The number of histologically confirmed complete remissions under imiquimod.
Time Frame
Baseline, 2 months till 3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brigitte Dréno, MD, PhD
Organizational Affiliation
Nantes University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU
City
Besançon
Country
France
Facility Name
CHU Hôpital Haut-Lévêque
City
Bordeaux
Country
France
Facility Name
CHU Hôpital Saint André
City
Bordeaux
Country
France
Facility Name
AP-HP Hôpital Ambroise Paré
City
Boulogne Billancourt
Country
France
Facility Name
CHU
City
Brest
Country
France
Facility Name
CHU Michallon
City
Grenoble
Country
France
Facility Name
CH
City
Le Mans
Country
France
Facility Name
CHRU
City
Lille
Country
France
Facility Name
CHU
City
Limoges
Country
France
Facility Name
CHU
City
Lyon
Country
France
Facility Name
AP-HM
City
Marseille
Country
France
Facility Name
CHU
City
Montpellier
Country
France
Facility Name
Centre Hospitalier Universitaire de Nantes
City
Nantes
ZIP/Postal Code
44000
Country
France
Facility Name
CHU
City
Nice
Country
France
Facility Name
CHU
City
Orléans
Country
France
Facility Name
AP-HP Hôpital Saint Louis
City
Paris
Country
France
Facility Name
CHU Milétrie
City
Poitiers
Country
France
Facility Name
CHU
City
Reims
Country
France
Facility Name
CHU Pontchaillou
City
Rennes
Country
France
Facility Name
CHU
City
Saint-Etienne
Country
France
Facility Name
Chu (Iucto)
City
Toulouse
Country
France
Facility Name
CHU
City
Tours
Country
France
12. IPD Sharing Statement
Learn more about this trial
Relevance of Imiquimod as Neo-adjuvant Treatment to Reduce Excision Size and the Risk of Intralesional Excision in Lentigo Malignant of the Face
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