ICG Fluorescence Technique for the Detection of Sentinel Lymph Nodes

Malignant Neoplasm of Breast Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01395706
• Other study ID #: PULSION-001
• Status: Not yet recruiting
• Phase: Phase 2
• First received: July 14, 2011
• Last updated: July 15, 2011
• Start date: September 2011
• Est. completion date: March 2012

Study information

• Verified date: July 2011
• Source: Pulsion Medical Systems SE
• Contact: Diethelm Wallwiener, Prof. Dr.
• Phone: ++49-7071-29-82-0
• Email: Diethelm.Wallwiener[@]med.uni-tuebingen.de
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 125
• Est. completion date: March 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Breast Neoplasms
• Malignant Neoplasm of Breast
• Neoplasms

Intervention

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

Locations

Country	Name	City	State
Germany	University Department of Gynecology and Obstetrics	Tuebingen

Sponsors (1)

Lead Sponsor	Collaborator
Pulsion Medical Systems SE

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sensitivity using ICG	Intraindividual: number of tumour-involved fluorescent positive sentinel lymph nodes / total number tumour-involved Technetium positive sentinel lymph nodes	5 to 11 days	No
Secondary	Specificity using ICG	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	5 to 11 days	Yes