ICG Fluorescence Technique for the Detection of Sentinel Lymph Nodes

Sponsor

Pulsion Medical Systems SE (Industry)

Overall Status

Unknown status

CT.gov ID

NCT01395706

Collaborator

(none)

125

Enrollment

Location

Arm

Duration (Months)

20.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Objectives of Clinical Trial

The main objective of this clinical trial is to show the efficacy of fluorescence lymphangiography with indocyanine green (ICG) for the detection of sentinel lymph nodes.

Condition or Disease	Intervention/Treatment	Phase
Malignant Neoplasm of Breast	Procedure: ICG Fluorescence technique	Phase 2

Detailed Description

Considering the high diagnostic accuracy and less vulnerable staging and therapy procedures, SLNB has rapidly become the state of the art diagnostic for axillary staging in early breast cancer.

Prior surgery, the so called sentinel lymph nodes are detected, harvested and histopathologically examined. The histopathologic status of the sentinel node thereby accurately reflects the status of the remaining axillary nodes. The sentinel lymph node biopsy allows minimizing risks and burdens for patients who very likely have no metastasis in the axillary lymph nodes sparing the ALND and reducing the risk of surgery and postoperative lymph oedema for instance. Contrarily to former procedure where an axillary lymph node dissection (ALND) was done each time, an ALND now only follows if the detected sentinel lymph node is metastatic.

Routinely sentinel lymph nodes are mapped using radiocolloid tracers such as technetium, sometimes combined with a blue dye.

However the infrastructure for a radioactive tracing is complex and not available easily:

special techniques and equipment for the manufacturing of the radiocolloid as well as training in the use with radioisotopes are needed. For example, the application of radioactive markers needs a ready access to a nuclear medicine department, a pre-operative visit and an effective coordination between the involved disciplinesis. As these radioisotopes are formed by specialised, rare industry facilities availability is heavenly dependend and lack of radioisotopes with shortages in diagnostic procedures has already been reported. Furthermore radiocolloid mapping is associated with radioactive exposure of the concerned patients and health workers and imposes problems with surgical waste disposal.

Novel methods for detecting sentinel lymph nodes which waive the pre-operative injection of the radioactive marker are currently investigated. One of these new methods is the application of a fluorescence marker for SLN detection.

In this clinical trial a novel method for detecting the sentinel lymph node using indocyanine green, a fluorescent molecule shall by investigated.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

125 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Determination of the Sensitifity of ICG Fluorescence Technique for the Detection of Sentinel Lymph Nodes in Breast Cancer - a Monocenter Prospective Open-label Clinical Trial

Study Start Date :

Sep 1, 2011

Anticipated Primary Completion Date :

Feb 1, 2012

Anticipated Study Completion Date :

Mar 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ICG flourescence technique This is an uncontrolled, non-randomised, open-label, monocenter clinical trial. A total of n=125 subjects will participate in this clinical trial. No clinical trial participant will be allowed to be included in this trial more than once.	Procedure: ICG Fluorescence technique This is an uncontrolled, non-randomised, open-label, monocenter clinical trial. A total of n=125 subjects will participate in this clinical trial. No clinical trial participant will be allowed to be included in this trial more than once. 10 mg (5mg/ml)per injection are applicated Other Names: Indocyanine Green (ICG)

Arm

Intervention/Treatment

Experimental: ICG flourescence technique

This is an uncontrolled, non-randomised, open-label, monocenter clinical trial. A total of n=125 subjects will participate in this clinical trial. No clinical trial participant will be allowed to be included in this trial more than once.

Procedure: ICG Fluorescence technique

Other Names:

Indocyanine Green (ICG)

Outcome Measures

Primary Outcome Measures

Sensitivity using ICG [5 to 11 days]
Intraindividual: number of tumour-involved fluorescent positive sentinel lymph nodes / total number tumour-involved Technetium positive sentinel lymph nodes

Secondary Outcome Measures

Specificity using ICG [5 to 11 days]
Specificity using ICG: number of patients with fluorescent positive sentinel lymph nodes that are not tumour - involved / number of patients with Tc positive SLN False negative rate: Number of patients where no sentinel lymph node is detected with Tc but with ICG / total number of patients with at least one Tc positive SLN Detection rate for the SLN using the ICG fluorescence imaging method: number of patients with at least one fluorescent sentinel lymph node per total number of patients treated with ICG Safety and tolerability of the IMP

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Early breast cancer: histopathologically confirmed diagnosis, maximum tumour stage T1 and T2, therefore diameter < 5 cm, unifocal tumour or multifocal tumour Grading G1-G3, invasive ductal and / or invasive lobar carcinoma ≤ 5 cm diameter
Indicated sentinel lymph node biopsy as part of the patient's routine management for breast cancer
Age: 18 - 80 years, inclusive
Gender: male and female
BMI: ≤ 30
Non-smoker (for at least the previous 3 months)
General operability
Intact site-specific anatomy at the concerned breast and /or axilla for ensuring an adequate lymphangiography
Performance of investigations with radioactive traced iodide at least 1 week before and 1 week after ICG application
No clinically significant findings in the routine blood examinations
Female subjects with childbearing potential must have a negative pregnancy test prior Tc application and must be either at least two years postmenopausal or using a highly effective mean of birth control (birth control that, alone or in combination, result in a low failure rate of less than 1 percent per year when used consistently and correctly):
hormonal method of contraception,
surgical sterility,
double barrier methods,
intrauterine contraceptive device,
lifestyle with a personal choice of abstinence,
bilateral vasectomy of sexual partner at least 3 months prior to enrolment in combination with barrier methods
Willing and able to complete screening and study procedures, as described in the protocol
Signed written informed consent to participate in this clinical trial

Exclusion Criteria:

Breast cancer: stage T3 or T4 carcinoma, inflammatory or exulcerated mamma carcinoma
Former operation in axilla
Any previous radiotherapy at the concerned breast and / or axilla and / or chestwall
Definite lymph node metastases (ultrasound and / or fine-needle aspiration) (definite nodal positive patients in fine-needle aspiration)
Contraindication for technetium imaging
History of allergy or hypersensitivity against the investigational medicinal products (its active substance or ingredients)
History of intolerability to ICG-Pulsion during a previous injection, as this may lead to serious anaphylactic reactions
History of allergic diseases / hypersensitivities, unless the investigator considers the allergic disease as clinically irrelevant for the purpose of this clinical trial
Allergy to iodine or to shellfish
Any other contraindication to one of the investigational medicinal products as described in their Summary of Product Characteristics
Apparent hyperthyroidism, autonomous thyroid adenoma, unifocal, multifocal or disseminated autonomies of the thyroid gland
Advanced renal impairment (creatinine > 1,5mg/dl)
Complete lymphatic obstruction
All clinically relevant internal medicinal diseases, cardiac or renal that could impair the outcome of the clinical trial or that in the investigator's mind are not compatible with participation for medical reasons
Acute inflammatory or febrile illness
Evidence of local inflammation at the site of surgery
Concurrent medication or any medication during the 2 weeks preceeding the enrolment which reduce or increase the extinction of ICG (i.e. anticonvulsants, haloperidol)
Current or recent history of illicit drug or alcohol abuse, or dependence as defined as the continued use of alcohol or drugs despite the development of social, legal, or health problems
Psychiatric or cognitive impairment that, in the opinion of the investigator, would interfere with the subject's ability to comply with the study requirements (e.g. Alzheimer's disease)
Pregnancy, breastfeeding
Inability to understand the nature and the extent of the trial and the procedures required
Missing signed written informed consent to participate in the clinical trial
Participation in a drug trial during the whole clinical trial