Lymph Node Identification in Skin Malignancy Using ICG Transcutaneously Study (LIMIT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03545334
Recruitment Status : Recruiting
First Posted : June 4, 2018
Last Update Posted : June 19, 2018
Information provided by (Responsible Party):
University Hospital Inselspital, Berne

Brief Summary:
A clinical, prospective, single-arm, single-blind, single-center, diagnostic sensitivity study. The primary objective is to evaluate a new technique in transcutaneous Sentinel lymph nodes identification over the current gold standard. The surgery will be performed according to the standard surgical procedure with a combination of gamma probe navigation and fluorescence imaging The required sample size was determined with 93 lymph nodes to be examined.

Condition or disease Intervention/treatment Phase
Melanoma of Skin Staging (Diagnosis) Merkel Cell Carcinoma Diagnostic Test: VS3 - 3DHD camera Not Applicable

Detailed Description:
Switzerland has the highest incidence of melanoma in Europe (19.2 per 100,000) and this carries the poorest prognosis of all the skin cancers. The current treatment is dependent on the histological diagnosis following a biopsy and is determined primarily on tumour thickness (Breslow score), the rate the cancerous cells are dividing (mitotic rate), presence of ulceration, presence of regression, and age of patient. Initial treatment is through surgical excision with a safety margin of macroscopically normal skin surrounding the tumour. If the tumour thickness is more than 1 mm or more than 0.7 mm in association with high mitotic rate in younger patients, ulceration, regression or Clark level IV / V, the current cancer network guidelines suggest that the patient is offered an Sentinel lymph nodes biopsy as this is most likely to be the first site any metastasis spreads to. Merkel cell carcinoma is a highly aggressive neuroendocrine skin tumor with a mortality of approximately 33% at 3 years. Because of the frequent lymphatic metastasis, a Sentinel lymph nodes biopsy is highly recommended in all the patients to better assess their prognosis. The current gold standard technique to identify SLNs is to inject the radioisotope Technetium 99m intra-dermally around the location of the primary tumour. The patient is then scanned using multiple X rays to detect the location of the Sentinel lymph node at approximately 30 and 120 minutes. Other teams have tried to transcutaneously identify Sentinel lymph nodes with ICG and NIRFI, but they concluded that ICG fluorescence technique is not reliable in patients with a high BMI or in patients with a primary tumor draining in the axillary node field. This study aims to evaluate a medical device that uses improved technology compared to previous studies (stereoscopic 3D high definition for both fluorescence and visible light imaging). The investigators hope is that by applying similar principles, Sentinel lymph nodes may be identified transcutaneously using fluorescent dye injections and NIRFI (with VS3-3DHD camera).

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 93 participants
Intervention Model: Single Group Assignment
Intervention Model Description: A diagnostic sensitivity study to analyse the ability of intradermally administered indocyanine green (ICG) and near infrared fluorescence imaging (NIRFI) to transcutaneously identify sentinel lymph nodes (SLNs) in malignant melanoma and Merkel cell carcinoma - after intradermally administered injection of technetium 99m and traditional lymphoscintigraphy (LS)
Masking: None (Open Label)
Masking Description: The surgeons performing SLNB will be the blinded persons. The results of the lymphoscintigraphy will not be marked on the patient's skin as usual and no preoperative access to the images will be granted to the surgeons.
Primary Purpose: Diagnostic
Official Title: Lymph Node Identification in Skin Malignancy Using Indocyanine Green Transcutaneously (LIMIT) Study
Actual Study Start Date : September 1, 2017
Estimated Primary Completion Date : February 28, 2019
Estimated Study Completion Date : June 30, 2019

Arm Intervention/treatment
Experimental: ICG and VS3-3DHD camera

After induction of anaesthesia, standard procedures for injection of a single dose Indocyanine green (ICG) intradermally are performed according to product description and hospital SOPs. Dose depending on the length of the lesion/scar, 1-4 ml of ICG was injected intradermally (5 mg/ml). Duration of the whole procedure about 20 - 30 minutes.

After ICG injection the possible draining lymphatic basins from the primary scar (i.e. axillae, inguinal, popliteal and neck regions) are scanned with the VS3-3DHD camera and all transcutaneous fluorescence spots recorded in the CRF. The scanning is discontinued after a maximum of 15 minutes regardless of findings.

Diagnostic Test: VS3 - 3DHD camera
Injection of ICG intradermally around the scar of the primary excision of the tumour and transcutaneous assessment of fluorescence with the VS3-3DHD camera (Visionsense™ VS3 - Stereoscopic High Definition Visualisation System ).
Other Name: Indocyanin green (ICG)

Primary Outcome Measures :
  1. Correlation of sentinel lymph nodes identified by lymphoscintigraphy vs. VisionSense near-infrared-fluorescence-imaging. [ Time Frame: one hour ]
    To determine whether the VisionSense NIRFI technology can transcutaneously identify SLNs as effectively as LS.

Secondary Outcome Measures :
  1. Correlation of sentinel lymph nodes identified by lymphoscintigraphy vs. VisionSense near-infrared-fluorescence-imaging in specific anatomical locations and in defined patient groups (e.g. groups defined based on BMI, sex, age). [ Time Frame: one hour ]
    The study seeks primarily to determine ability of the VisionSense NIRFI technology to transcutaneously identify SLNs as effectively as LS.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Malignant melanoma patients having one of the following characteristics:

    1. Breslow score ≥ 1 mm
    2. Breslow score ≥ 0.7 mm associated with ulceration
    3. Breslow score ≥ 0.7 mm associated with regression
    4. Breslow score ≥ 0.7 mm associated with Clark Level IV / V
    5. Breslow score ≥ 0.7 mm associated with mitotic rate ≥ 1/mm2 in young patients
  2. Merkel cell carcinoma

Exclusion Criteria:

  • Age < 18 years
  • Pregnancy and breastfeeding (pregnancy test to be performed for women of child-bearing potential, defined as women who are not surgically sterilized/ hysterectomized, and/ or who are postmenopausal for less than 12 months)
  • Known allergy to ICG or Iodine
  • Previous chemotherapy, radiotherapy or surgery to the lymph nodes of interest
  • Lack of capacity to provide informed consent
  • Current enrolment in any other interventional study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03545334

Contact: Radu Olariu, MD +41316328014
Contact: Ioana Lese, MD +41316328014

Inselspital, University Hospital Bern, University of Bern Recruiting
Bern, Kanton Bern, Switzerland, 3010
Contact: Radu Olariu    +41316328014   
Contact: Ioana Lese    +41316328014   
Sponsors and Collaborators
University Hospital Inselspital, Berne
Study Director: Mihai A. Constantinescu, Professor Director of Clinic for Plastic and Reconstructive Surgery, Inselspital Bern, Switzerland
Principal Investigator: Radu Olariu, MD Deputy chief physician of Clinic for Plastic and Reconstructive Surgery, Inselspital Bern, Switzerland

Responsible Party: University Hospital Inselspital, Berne Identifier: NCT03545334     History of Changes
Other Study ID Numbers: KEK-Nr. 2016-01746
First Posted: June 4, 2018    Key Record Dates
Last Update Posted: June 19, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital Inselspital, Berne:
Transcutaneous, SLN, melanoma, Merkel cell carcinoma

Additional relevant MeSH terms:
Carcinoma, Merkel Cell
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Polyomavirus Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Carcinoma, Neuroendocrine
Neoplasms, Glandular and Epithelial
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents