Clinical trial NCT02419807
Conditions: Stage I Breast Cancer Stage II Breast Cancer
Keywords: Near Infrared Fluorescence Imaging Indocyanine Green axillary lymph node mapping Mastectomy, Segmental Sentinel Lymph Node Biopsy Lumpectomy
Sponsor: Case Comprehensive Cancer Center
Start date: 2015-02-17; Completion date: 2019-02-01
Enrollment: 102 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This clinical trial will enroll up to 130 adult women with a confirmed diagnosis of clinical stage 1 or 2 breast cancer who are undergoing breast cancer surgery with lumpectomy or mastectomy and planned axillary sentinel node biopsy procedure. Participants will undergo lymphatic mapping with technetium Tc-99m (99mTc) sulfur colloid in accordance with routine clinical practice. Injections of 99mTc sulfur colloid will take place the afternoon prior to planned next morning surgery or on the morning of surgery. Participants will undergo lymphoscintigraphy in accordance with standard clinical practice.

Immediately prior to operation, after the induction of anesthesia in the operating room, up to 1cc of 0.5% indocyanine green (ICG) solution will be injected subdermally close to the tumor or into the subareolar region after disinfection of the breast skin. ICG movement will be facilitated by manual massage and monitored with fluorescence imaging. ICG fluorescence will be elicited and detected by Photodynamic Eye (PDE) camera. The lymphatic drainage, made evident by the fluorescent dye, will be monitored in real time on a monitor. The fluorescence will be followed towards the armpit region (axilla) and time for the fluorescence to reach the axilla will be recorded. Following standard practice, an incision will be made in the armpit region. Fluorescent lymph nodes (ICG positive) will be localized and removed and analyzed by a pathologist. Node removal will continue until no residual fluorescence is visible in the axilla. Removed nodes will be tested for radioactivity using a standard gamma-detecting probe and the counts per minute will be recorded. Finally, the armpit region will be inspected with the gamma probe to determine if there are any residual radioactive nodes. Residual sentinel nodes (the first node to receive lymph from a tumor) will be removed. For the purposes of this study, the sentinel status of a node will be defined as being flagged as sentinel by either one or both of the ICG or 99mTc methods. The goal of the project is to confirm that axillary lymphatic mapping with ICG leads to similar nodes being labeled as sentinel as lymphatic mapping with 99mTc-labeled radiotracer.

Detailed description:
PRIMARY OBJECTIVES:

I. To confirm that axillary lymphatic mapping with indocyanine green solution (ICG) solution leads to a similar number of nodes being labeled as sentinel as lymphatic mapping with 99mTc-labeled (technetium Tc-99m sulfur colloid) radiotracer.

OUTLINE:

Participants receive technetium Tc-99m sulfur colloid injection and undergo lymphoscintigraphy according to clinical practice. Prior to surgery, participants also receive indocyanine green solution subdermally close to the tumor or into subareolar region of the breast skin. Participants then undergo axillary sentinel node biopsy and surgery.

Arms: arm 1: Participants receive technetium Tc-99m sulfur colloid injection and undergo lymphoscintigraphy according to clinical practice. Prior to surgery, participants also receive indocyanine green solution subdermally close to the tumor or into subareolar region of the breast skin. Participants then undergo Axillary Lymph Node Biopsy and surgery.
Interventions: intervention 1: Indocyanine Green Solution intervention 2: Technetium Tc-99m Sulfur Colloid intervention 3: Lymphoscintigraphy intervention 4: Axillary Lymph Node Biopsy
Intervention descriptions: intervention 1: Given subdermally intervention 2: Given via injection intervention 3: This is a method used to check the lymph system for disease. A radioactive substance that flows through the lymph ducts and can be taken up by lymph nodes is injected into the body. A scanner or probe is used to follow the movement of this substance on a computer screen. Lymphoscintigraphy is used to find the sentinel lymph node (the first node to receive lymph from a tumor), which may be removed and checked for tumor cells. Lymphoscintigraphy is also used to diagnose certain diseases or conditions, such as lymphoma or lymphedema. intervention 4: Undergo biopsy

Protocol documents:
Prot_SAP_000.pdf: 
CASE 10114 Protocol v5 11-18-16                                                                                           Page 1 of 8 
CASE COMPREHENSIVE CANCER CENTER 
__________________________________________________________________ 
 
 
STUDY NUMBER:  
CASE 10114 
 
STUDY TITLE: 
 
COMPARISON OF USE OF INDOCYANINE GREEN  
 
AND 99mTc-LABELED RADIOTRACER FOR AXILLARY 
LYMPHATIC MAPPING IN PATIENTS WITH BREAST 
CANCER 
 
PRINCIPAL INVESTIGATOR:  
Stephen R. Grobmyer, MD 
 
 
Department of General Surgery 
 
 
 
 
Cleveland Clinic  
 
 
 
 
9500 Euclid Avenue 
 
 
 
 
 
 
Cleveland, OH 44195 
 
 
 
 
 
 
(216) 636-2843, grobmys@ccf.org 
 
 
CO-PI: 
Alicia Fanning, MD  
 
Department of General Surgery 
 
 
 
Cleveland Clinic  
 
 
 
9500 Euclid Avenue 
 
 
 
 
 
Cleveland, OH 44195 
 
(216) 444-3334, fannina@ccf.org  
 
 
CO- INVESTIGATORS: 
Robyn Stewart, MD 
 
Department of General Surgery 
 
 
Cleveland Clinic  
 
 
 
9500 Euclid Avenue 
 
 
 
 
 
Cleveland, OH 44195 
 
(216) 444-6293, stewarr5@ccf.org 
                     
 
Stephanie Valente, DO 
 
Department of General Surgery 
 
 
Cleveland Clinic  
 
 
 
9500 Euclid Avenue 
 
 
 
 
 
Cleveland, OH 44195 
 
(216) 444-0769, valents3@ccf.org    
 
 
Diane Radford, MD 
 
Department of General Surgery 
 
Cleveland Clinic 
 
9500 Euclid Avenue 
 
Cleveland, OH 44195 
 
(216) 444-7506, radford2@ccf.org 
 
STATISTICIAN: 
Chao Tau 
 
Quantitative Health Sciences 
 
Cleveland Clinic 
 
9500 Euclid Avenue 
 
Cleveland, OH 44195 
 
(216) 445-8350, tuc@ccf.org 


CASE 10114 Protocol v5 11-18-16                                                                                           Page 2 of 8 
 
SUPPORT: 
CCF Breast Services Division 
 
CLINICAL FACILITY: 
Cleveland Clinic  
 
 
 
 
 
 
APPROVALS: 
Protocol Review and Monitoring Committee: Approved 
 
 
Cleveland Clinic IRB: Approved 
 
 
STUDY COORDINATORS:  
 
 
Courtney Yanda 
Cleveland Clinic 
9500 Euclid Avenue 
Cleveland, OH 44195 
(216) 444-3159, yandac@ccf.org 
Barbara BeVier 
Cleveland Clinic 
9500 Euclid Avenue 
Cleveland, OH 44195 
(216) 445-9159, bevierb@ccf.org 
 
 
 
TABLE OF CONTENTS 
 
 
 
        
 
 
1. 
Introduction  
 
 
 
 
 
 
 
 
 
 
 
2.0 
Objective 
 
 
 
 
 
 
 
 
 
 
 
3.0  
Study Design  
 
 
 
 
 
 
 
4.0 
Registration   
 
 
 
 
 
 
5.0 
Adverse Events and Reporting Requirements 
 
 
 
 
 
 
 
6.0             Data Reporting/Regulatory Considerations 
 
7.0 
Statistical Considerations 
 
 
 
 
 
 
 
 
 
 
 
 
8.0 
References 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


CASE 10114 Protocol v5 11-18-16                                                                                           Page 3 of 8 
1.0  
INTRODUCTION  
 
Background: 
Lymphatic mapping and axillary sentinel node biopsy has become a standard procedure for the 
surgical staging of patients with early stage breast cancer. It has been shown to be safe and accu-
rate and limits significantly the need for traditional axillary dissection in many patients with ear-
ly stage breast cancer. Traditionally, lymphatic mapping has involved the use of 99mTc-labeled 
radiotracer, or visible blue dye (methylene blue or isosulfan blue dye), or a combination of 
99mTc-labeled radiotracer and visible blue dye. Sentinel nodes are defined as axillary lymph 
nodes in which there is the accumulation of one or more of these tracers or dyes. 
The use of 99mTc-labeled radiotracer has a long history and is one of the more commonly used 
techniques of identifying sentinel nodes. However, the use of radiotracers has significant limita-
tions including the requirement for nuclear licensing; the need to prepare, handle and dispose of 
nuclear material, patient inconvenience with painful injections typically occurring before sur-
gery.  
There is a growing body of literature supporting the role of indocyanine green (ICG) dye for 
lymphatic mapping in Europe and Japan.  ICG is a fluorescent dye which can be detected using 
near infrared cameras.  The use of ICG in conjunction with a near infrared camera offers many 
potential advantages over the use of other techniques including the ability to inject the material 
while the patient is under anesthesia in the operating room, the ability to use near infrared imag-
ing to directly visualize lymphatic flow, and no special material handling is required.  ICG is 
FDA approved for vascular fluorescence and liver function studies in humans.   
ICG is a di-sulfonated heptamethine indocyanine with moderate optical properties, which emits 
≈ 800 nm. There are many uses for ICG during image-guided surgery. After intravenous injec-
tion, it can be used for NIR angiography of blood vessels, identification of the extrahepatic bile 
ducts, and identification of liver metastases. After subcutaneous injection, ICG has been reported 
by numerous authors to be safely used for sentinel lymph node (SLN) mapping(1-5) and as-
sessing lymphatic function.”(6)  
ICG has been used for the last 50+ years as a visible dye (green for ICG). Thus, there is an un-
precedented body of clinical data regarding their safety when used at millimolar concentrations.” 
(6) The use of ICG for lymphatic mapping in breast cancer patients has been demonstrated to be 
safe in numerous human studies performed in Asia and Europe (7-11). There is a recent retro-
spective case series report of using ICG for lymph node mapping in patients with melanoma 
from the Cleveland Clinic documenting its safety for in human use and lymphatic mapping (12).  
A recent study from Europe has demonstrated high concordance between the number nodes 
identified with ICG and 99mTc-labeled radiotracer (11).  There has been very limited work on 
the use of ICG for axillary lymph node mapping in humans in the United States, and no com-
parison studies of ICG with 99mTc-labeled radiotracer. The goal of the project is to confirm 
that axillary lymphatic mapping with ICG leads to a similar number of nodes being labeled 
as sentinel as lymphatic mapping with 99mTc-labeled radiotracer. Successful completion of 
this project would support the use of 99mTc-labeled radiotracer with ICG for LN mapping in 
early stage breast cancer patients. 
 


CASE 10114 Protocol v5 11-18-16                                                                                           Page 4 of 8 
 
2.0  
OBJECTIVE 
 
Hypothesis:  
ICG is equivalent to 99mTc-labeled radiotracer for axillary lymphatic mapping in patients 
with early stage breast cancer in terms of the numbers of nodes identified as sentinel by each 
method being similar.  
 
 
3.0 
STUDY DESIGN 
 
 
Methods: 
Patients with a confirmed diagnosis of clinical stage 1 or 2 breast cancer who are undergoing 
breast cancer surgery with lumpectomy or mastectomy and planned axillary sentinel node 
biopsy procedure will be eligible for the study.  Patients with cancer > 3cm, clinically posi-
tive nodes, prior surgery for breast cancer in the index breast, bilateral sentinel lymph node 
mapping, thyroid dysfunction, hypersensitivity to iodine, and hepatic or renal insufficiency 
will be excluded from the study.  
• 
We plan to enroll approximately 130 adult female patients who will be identified in the 
breast clinic at Cleveland Clinic Main Campus.   
• 
Informed consent will be obtained. 
• 
Patient information will be collected from the medical record and entered in Redcap. 
Patients will undergo lymphatic mapping with  99mTc sulfur colloid in accordance with routine 
clinical practice.  Injections of 99mTc sulfur colloid will take place the afternoon prior to planned 
next morning surgery or on the morning of surgery.  Patients will undergo lymphoscintigraphy in 
accordance with standard clinical practice.    
Immediately prior to operation, after the induction of anesthesia in the operating room, up to 1cc 
of 0.5% ICG solution will be injected subdermally or intradermally close to, above the tu-
mor,into the subareolar region or into the periareolar region after disinfection of the breast skin.  
ICG movement will be facilitated by manual massage and monitored with fluorescence imaging. 
ICG fluorescence will be elicited and detected by PDE camera (Hamamatsu Photonics, Hama-
matsu, Japan) which has FDA 510(k) clearance to visualize ICG fluorescence in the humans for 
vascular imaging.  The lymphatic drainage, made evident by the fluorescent dye, will be moni-
tored in real time on a monitor. The fluorescence will be followed towards the axilla and time for 
the fluorescence to reach the axilla will be recorded. In accordance with standard practice, an 
incision will be made in the axilla. Fluorescent lymph nodes (ICG positive) will be localized and 
removed and sent for pathologic analysis as per standard surgical practice. Node removal will 
continue until no residual fluorescence is visible in the axilla.  Excised nodes will be tested for 
radioactivity using a standard gamma-detecting probe and the counts per minute will be record-
ed. Finally, the axillary region will be inspected with the gamma probe to determine if there are 
any residual radioactive nodes. Residual sentinel nodes will be removed. With regard to radioac-
tivity, sentinel nodes are defined as any node with at least 10% of the hottest nodal counts.   
The following information will be collected for each removed node: 


CASE 10114 Protocol v5 11-18-16                                                                                           Page 5 of 8 
1. Fluorescence (yes/no)  
2. Counts per minute  
 
3. Pathologic status  of node (no metastasis, isolated tumor cells, micrometastasis, macro-
metastasis) 
Also collected will be procedure related data including transit time to axilla from time of injec-
tion, size of tumor, location of tumor, tumor histology, breast size, patient age, BMI. 
Consent: 
All subjects for this study will be provided a consent form describing this study and providing 
sufficient information for subjects to make an informed decision about their participation in this 
study.  The formal consent of a subject, using the IRB-approved consent form, will be obtained 
before that subject is submitted to any study procedure.  Consent will be obtained by the study 
coordinator or investigator of the study in the breast clinic on Main Campus at Cleveland Clinic.  
Consent will be documented in the medical record. 
Finance: 
There are no additional costs to the patients.  Mitaka USA will provide the PDE neo camera and 
ICG kit. 
Funding Source: 
CCF Breast Services Division 
 
 
4.0       REGISTRATION   
 
All patients enrolled on study will be entered into the Oncore database.  
 
 
5.0 
ADVERSE EVENTS AND REPORTING REQUIREMENTS  
 
 
Adverse Events and Data Monitoring Committee (DMC): 
Although we do not anticipate any adverse events, should any unexpected event occur, we will 
report the event in a timely manner per IRB policy.   A DMC will not be used during this study.  
 
 
6.0 
DATA REPORTING/REGULATORY CONSIDERATIONS 
  
Quality Control and Quality Assurance: 
The study coordinator will be responsible to keeping data confidentially documented and report-
ed in compliance with HIPAA and any other applicable regulatory requirements. The data will 
be kept for approximately 2 years after study completion, and will be accessible only to study 
staff.   


CASE 10114 Protocol v5 11-18-16                                                                                           Page 6 of 8 
Ethical Considerations: 
This study will be conducted according to US and international standards of Good Clinical Prac-
tice for all studies.  Applicable government regulations and Cleveland Clinic research policies 
and procedures will also be followed. 
This protocol and any amendments will be submitted to the Cleveland Clinic Institutional Re-
view Board (IRB) for formal approval to conduct the study.  The decision of the IRB concerning 
the conduct of the study will be made in writing to the investigator.  
  
7.0        STATISTICAL CONSIDERATIONS 
 
Sample size: 
The study will be designed to determine whether ICG based axillary sentinel lymph node biopsy 
yields a similar number of nodes as 99mTc sulfur colloid lymph node biopsy.  While SLN identi-
fication using 99mTc sulfur colloid is a common technique, neither of the two methods used in 
this study can be assumed to identify the “correct” set of nodes as sentinel. Therefore, for the 
purposes of this study, the sentinel status of a node will be defined as being flagged as sentinel 
by either one or both of the ICG or 99mTc methods.  By this definition, sentinel nodes identified 
by 99mTc but not ICG are an error by omission for the ICG method and nodes flagged by ICG but 
not 99mTc are an error by the 99mTc method. 
Let A be the number of Tc-positive and ICG-positive SNs detected, B be the number of Tc-
positive and ICG-negative SNs detected, and C be the number of Tc-negative and ICG-positive 
SNs detected. The total number (N) of SNs detected is therefore N = (A + B + C); the proportion 
of SNs (PTc) detected by the Tc method is (A + B)/N; and the proportion of SNs (PICG) detected 
by the ICG method is (A + C)/N. 
As significant differences in the numbers of nodes identified by each method would have impli-
cations regarding  the safety of ICG as a radiotracer, the null hypothesis is that the two methods 
identify an equivalent nodes of nodes as being sentinel nodes.  Here equivalence is defined as the 
difference in the proportions of nodes flagged between the 99mTc and ICG methods falling within 
an interval (−δ, +δ), where δ is taken to be 5%. Formally the null hypothesis for equivalence is:  
PICG − PTc < −δ and PICG − PTc ≥ +δ 
If the null hypothesis is rejected we may concluded for the hypothesis of equivalence that:  
δ < (PICG − PTc) < δ 
The equivalence hypothesis can be transformed into two one-sided hypotheses:  
(A) 
that the difference between the proportions is beyond the lower equivalence margin: null 
hypothesis A: PICG − PTc < −δ, which, if rejected, permits the conclusion PICG − PTc ≥ −δ 
(B) 
that the difference between the proportions is greater than the upper equivalence margin: 
null hypothesis B: PICG − PTc ≥ +δ which, if rejected, permits the conclusion 
PICG − PTc ≤ +δ. 


CASE 10114 Protocol v5 11-18-16                                                                                           Page 7 of 8 
Hypotheses A and B will be tested by comparing a two-sided 90% confidence interval (CI) for 
the difference in the proportions of SNs flagged by the two methods, with the 5% equivalence 
region (−δ, +δ). Tests for equivalence will be based on the methods for analyzing clustered 
paired binary data described in Obuchowski(13). To conclude for equivalence the 90% CI needs 
to be contained entirely within the defined equivalence region, which is equivalent to both null 
hypotheses (A) and (B) being rejected. 
To estimate the number of SNs that will need to be examined, we assumed a detection rate (A + 
B)/N of 97% for the Tc method, a discordance rate between the two methods (B + C)/N of 6%, 
and set δ at 5%. We found through simulation that 255 SNs will give adequate power (>80%) to 
demonstrate equivalence between the two methods, with a type I error (α) rate of 5%.  This is 
estimated to require ~130 patients as the average SN yield is expected to be approximately 2 per 
patient. 
 
 
8.0 
REFERENCES 
 
1. Nimura H, Narimiya N, Mitsumori N, et al. Infrared ray electronic endoscopy combined 
with indocyanine green injection for detection of sentinel nodes of patients with gastric 
cancer. Br J Surg. 2004;91:575–9.  
2. Miyashiro I, Miyoshi N, Hiratsuka M, et al. Detection of sentinel node in gastric cancer 
surgery by indocyanine green fluorescence imaging: comparison with infrared imaging. 
Ann Surg Oncol. 2008;15:1640–3.  
3. Kusano M, Tajima Y, Yamazaki K, et al. Sentinel node mapping guided by indocyanine 
green fluorescence imaging: a new method for sentinel node navigation surgery in gastro-
intestinal cancer. Dig Surg. 2008;25:103–8.  
4. Fujiwara M, Mizukami T, Suzuki A, Fukamizu H. Sentinel lymph node detection in skin 
cancer patients using real-time fluorescence navigation with indocyanine green: prelimi-
nary experience. J Plast Reconstr Aesthet Surg. 2008  
5. Tsujino Y, Mizumoto K, Matsuzaka Y, et al. Fluorescence navigation with indocyanine 
green for detecting sentinel nodes in extramammary Paget’s disease and squamous cell 
carcinoma. J Dermatol. 2009;36:90–4.  
6. Gioux et al. “Image-Guided Surgery using Invisible Near Infrared Light: Fundamentals 
of Clinical Translation.” Mol. Imaging 9(5): 237, 2011. 
7. Tong et al. “Use of Fluorescence Imaging in Combination with Patent Blue Dye versus 
Patent Blue Dye Alone in Sentinel Lymph Node Biopsy in Breast Cancer.” Journal of 
Breast Cancer. 17(3):250, 2014.  
8. Chi et al. “Use of Indocyanine Green for Detecting the Sentinel Lymph Node in Breast 
Cancer Patients: From Preclinical Evaluation to Clinical Validation.” PLOS One. 8(12): 
e83927, 2013. 


CASE 10114 Protocol v5 11-18-16                                                                                           Page 8 of 8 
9. Wishart et al. “A Feasibility Study of ICG Fluorescence Mapping for Sentinel Node De-
tection in Early Breast Cancer.” EJSO. 38: 651, 2012.  
10.  Sugie, T et al. “Comparison of the ICG Fluroscence and Blue Dye Methods in Detection 
of Sentinel Lymph Nodes in Early Stage Breast Cancer.” Ann Surg Onc. 20: 2213, 2013.  
11. Ballardini, B. et al. “The ICG Method is Equivalent to the 99Tc-Labeled Radiotracer 
Method for Identifying the Sentinel Node in Breast Cancer: A Concordance and Valida-
tion Study.” EJSO 39: 1332, 2013.  
12. Korn et al. “ING SPY Elite-Assisted Sentinel Lymph Node Biopsy in Cutaneous Mela-
noma.” Plast Recontr Surg. 133:914, 2014. 
13. Obuchowski, NA.  On the Comparison of Correlated Proportions for Clustered Data. Stat 
Med 1998 Jul 15;17(13): 1495-507. 
14. Samorani et al. “The use of indocyanine green to detect sentinel nodes in breast cancer: A 
prospective study.” EJSO. 41: 64, 2014. 

ICF_001.pdf: 
Dr Grobmyer, PI 
Consent Version date August 31, 2016
         Page 1 of 6 
The Cleveland Clinic Foundation 
Consent to Participate in a Research Study 
Study title:  Comparison of use of indocyanine green (ICG) and 99mTc-labeled 
radiotracer for axillary lymphatic mapping in patients with  
breast cancer   
Principal Investigator: Stephen R. Grobmyer, MD (phone 216-636-2843)  
Study Coordinator:     Courtney Yanda (phone 216-444-3159) 
You are being invited to participate in a research study.  A research study is designed to 
answer specific questions about new ways to prevent, detect, and treat disease.  Being 
in a research study is different from being a patient.  The purpose of this document is to 
provide a written summary of the discussion and exchange of research information you 
had with the research team.  It is also for use as a reference during the study.   
Please note: 
x
You are being asked to participate in a research study 
x
Ask as many questions as needed so you can make an informed decision. 
x
Carefully consider the risks, benefits, and alternatives of the research 
x
Your decision to participate is completely voluntary and will have no effect 
on the quality of your medical care if you choose not to participate. You 
can also withdraw from the study at anytime. 
This research study has been approved by the Institutional Review Board (IRB).  The 
IRB is a committee that reviews human research studies to ensure the safety and 
welfare of research volunteers are protected in accordance with federal human subject 
regulations and ethical principles. 
1. INFORMATION ON THE RESEARCH 
Why is the research study being done? 
The purpose of this study is to evaluate the usefulness of indocyanine green (ICG) dye 
for lymph node mapping in patients with breast cancer.  ICG will be compared to 
lymphatic mapping with 99mTc-labeled radiotracer, which is standard of care.  
ICG is a dye which can be seen using a camera called a near infrared (or “PDE”). The 
use of ICG with this camera offers the ability to inject the dye while you are under 
anesthesia in the operating room and to see the dye move to the lymph nodes.  
The use of ICG and the near infrared camera are cleared by the Food and Drug 
Administration (FDA) for use in humans for vascular tests, and ICG is cleared for use in 
liver function tests, but these have not yet been cleared for lymph node mapping in 
patients with breast cancer. 
CCF IRB #: 15-168
Approval Date: 2/13/2018
Expiration Date: 2/12/2019


Dr Grobmyer, PI 
Consent Version date August 31, 2016
         Page 2 of 6 
This research will take place only at the Cleveland Clinic and will include about 130 
patients.  
You are being asked to participate in this study because you are scheduled to undergo 
breast cancer surgery with lumpectomy or mastectomy and planned axillary sentinel 
node biopsy procedure.  
What is involved if you decide to take part in this research study? 
You will receive the same standard of care treatment whether or not you decide to 
participate in this study.  
A member of the study staff will review the study with you and answer any questions 
you may have.  If you agree to participate, we will ask you to sign this consent form 
before having any study-related tests performed.  Your participation will include the 
standard of care pre-operative visit, and operating room time (which is not extended 
with this research procedure).  The following will occur: 
In accordance with routine clinical practice, you will undergo lymphatic mapping with 
99mTc sulfur colloid.  Injections of 99mTc sulfur colloid will take place the afternoon 
before your planned next morning surgery, or on the morning of surgery.  This is within 
current standard of care and will be explained by your surgeon. 
x There is more than one accepted method to map the lymph system for this 
procedure. This study will use only 99mTc sulfur colloid in order to standardize 
comparison. If you choose not to participate, your surgeon may use 99mTc sulfur 
colloid alone or in combination with blue dye or blue dye alone.  
Immediately prior to operation, after you receive anesthesia in the operating room, a 
small amount of ICG solution will be injected under the skin close to the tumor after 
disinfection of the breast skin.  Movement of the ICG dye under the skin (to your 
underarm region) will be seen and monitored by the PDE camera (fluorescence 
imaging).  The ICG injection and PDE monitoring is the research-related part of your 
procedure. 
In accordance with standard practice, an incision will be made to remove the fluorescent 
lymph nodes which uptake ICG and they will be sent for analysis.  The lymph nodes that 
were removed will be tested for radioactivity.  Finally, the region will be inspected to 
determine if there are any residual radioactive nodes, and if so, these nodes will be 
removed.  
The study staff will collect the data from your surgical procedure, along with the 
following information from your medical record:  
x The amount of time for ICG to move from the injection site to the lymph nodes 
x size of tumor 
x location of tumor 
x tumor histology 
CCF IRB #: 15-168
Approval Date: 2/13/2018
Expiration Date: 2/12/2019


Dr Grobmyer, PI 
Consent Version date August 31, 2016
         Page 3 of 6 
x breast size 
x age and BMI (height and weight) 
Your information will be stored in a secure fashion for use as part of this study.  This will 
be recorded in a secure Cleveland Clinic database.  The database will not include your 
name but will include your medical record number and the information listed above.  
The data will be kept for approximately 2 years, and only the study staff will have 
access to this database.  
The results of this research may be presented at meetings or in publications; however, 
all personal identifying information will be stripped so that your results cannot be 
associated with you. 
2. ALTERNATIVES 
What are the alternatives to participation in the research study? 
You can choose not to participate in this research study. If you choose not to 
participate, this will not impact your current or future care at the Cleveland Clinic. 
3. RISKS 
What are the risks of participating in the research study? 
Risk of indocyanine green (ICG) 
Rare anaphylactic reactions (breathing problems) or urticarial (itching) reactions have 
been reported in patients with or without history of allergy to iodides.  If such reactions 
occur, treatment with the appropriate agents (epinephrine, antihistamines, and 
corticosteroids) will be given in the operating room.  
Confidentiality of Your Data 
Your privacy is very important to us and we will use many safety measures to protect 
your privacy.  There is a potential risk of loss of confidentiality of your data.  Information 
from which you may be personally identified will be maintained in a confidential, locked 
file at the Cleveland Clinic, and will not be disclosed to third parties except with your 
permission or as may be required by law.  There also may be other privacy risks that we 
have not foreseen. 
4. BENEFITS 
What are possible benefits of participating in the research? 
Information gained from this research study may be used to help others in the future by 
providing a better diagnostic test for breast cancer. 
5. COSTS 
CCF IRB #: 15-168
Approval Date: 2/13/2018
Expiration Date: 2/12/2019


Dr Grobmyer, PI 
Consent Version date August 31, 2016
         Page 4 of 6 
Are there any costs to you if you participate in this study? 
There are no additional costs to you for participation in this research study.  The study 
related procedures will be provided at no cost to you or your insurance company.  The 
ICG materials will be provided by Mitaka, USA.   
The cost for routine tests and services that would normally be performed even if you 
don’t participate in the study will be billed to you or your insurance provider.   
6. COMPENSATION 
Are there any payments to you if you participate in this study?
You will not be paid for your participation in this research. There are no plans to provide 
financial compensation to you. 
7. RESEARCH RELATED INJURY 
What will happen if you are injured as a result of taking part in the research? 
If you experience physical injury or illness as a result of participating in this research 
study, medical care is available at the Cleveland Clinic or elsewhere; however, the 
Cleveland Clinic has no plans to provide free care or compensation for lost wages.  You 
are not waiving any legal rights by signing this form.  Further information about 
research-related injuries is available from the Office of the Institutional Review Board 
(216-444-2924). 
8. PRIVACY AND CONFIDENTIALITY 
Authorization to Use or Disclose (Release) Health Information that Identifies You 
for a Research Study
If you volunteer to participate in this research, your protected health information (PHI) 
that identifies you will be used or disclosed to Dr. Stephen R. Grobmyer and the 
research staff at Cleveland Clinic for the purposes of this research and to Case Western 
Reserve University for administration. 
A note will be placed in your medical record to indicate your participation in this study.   
In addition to the investigators and research staff listed above, your PHI may be looked 
at by other groups involved with the study such as the Cleveland Clinic Institutional 
Review Board, and the Case Comprehensive Cancer Center Protocol Review and 
Monitoring Committee.  Your PHI may also be used by and/or disclosed (released) to 
the Food and Drug Administration; the Department of Health and Human Services; the 
National Cancer Institute (NCI); and Data Safety and Monitoring Boards 
Once your personal health information is released it may be re-disclosed and no longer 
protected by privacy laws. 
Your research information may be used and disclosed indefinitely, but you may stop 
these uses and disclosures at any time by writing to Stephen R. Grobmyer, MD, 
Department of General Surgery, Cleveland Clinic, 9500 Euclid Ave, A81, Cleveland, 
CCF IRB #: 15-168
Approval Date: 2/13/2018
Expiration Date: 2/12/2019


Dr Grobmyer, PI 
Consent Version date August 31, 2016
         Page 5 of 6 
OH, 44195.  Your participation in the research will stop, but any information previously 
recorded about you cannot be removed from the records and will continue to be used as 
part of this research.  Also, information already disclosed outside the Cleveland Clinic 
cannot be retrieved.  This will not affect your rights to treatment or benefits outside the 
research study.    
The Cleveland Clinic will not use your information collected in this study for another 
research purpose without your written permission, unless the Cleveland Clinic 
Institutional Review Board (IRB) assures your privacy and confidentiality is protected.  
The IRB is a committee whose job it is to protect the safety and welfare of research 
subjects. 
By signing this informed consent form, you are authorizing such access to your research 
and medical record information.  If you choose not to sign this consent form, you will not 
be able to participate in this research study.  This Authorization does not have an 
expiration date. 
9. QUESTIONS 
Who do you call if you have any questions or problems? 
If you have any questions about the research or develop a research related problem, 
you should contact Dr Stephen Grobmyer at 216-636-2843 during normal business 
hours.  If you need assistance after 5pm, on holiday or weekend, call the Cleveland 
Clinic main hospital number at 216-444-2200 and ask for the General Surgery Resident 
on Call. If you have questions about your rights as a research subject, you should 
contact the Institutional Review Board at (216) 444-2924.
Where Can I Get More Information? 
You may call the National Cancer Institute’s Cancer Information Services at: 
 
1-800-4-CANCER (1-800-422-6237) or TTY: 1-800-332-8615 
You may also visit the NCI website at http://cancer.gov 
x For NCI’s clinical trials information, go to: http://cancer.gov/clinicaltrials 
x For NCI’s general information about cancer, go to http://cancer.gov/cancerinfo 
US National Institutes of Health (NIH) Clinical Trial Database 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 
required by U.S. law.  This Website will not include information that can identify you.  At 
most, the Website will include a summary of the results.  You can search the Website at 
any time. 
10. VOLUNTARY PARTICIPATION   
CCF IRB #: 15-168
Approval Date: 2/13/2018
Expiration Date: 2/12/2019


Dr Grobmyer, PI 
Consent Version date August 31, 2016
         Page 6 of 6 
What are your rights as a research participant? 
Taking part in this study is voluntary.  You will be told of any new, relevant information 
from the research that may affect your health, welfare, or willingness to continue in this 
study.  You may choose not to take part or may leave the study at any time.  
Withdrawing from the study will not result in any penalty or loss of benefits to which you 
are entitled.   
11. SIGNATURES 
Statement of Participant 
I have read and have had verbally explained to me the above information and have had 
all my questions answered to my satisfaction.  I understand that my participation is 
voluntary and that I may stop my participation in the study at any time.  Signing this form 
does not waive any of my legal rights.  I understand that a copy of this consent will be 
provided to me.  By signing below, I agree to take part in this research study.   
_________________________________ 
Printed name of Participant 
_________________________________ 
 
___________ 
 
 
Participant Signature 
 
 
                      Date  
 
 
Statement of Person Conducting Informed Consent Discussion 
I have discussed the information contained in this document with the participant and it is 
my opinion that the participant understands the risks, benefits, alternatives and 
procedures involved with this research study. 
_________________________________ 
Printed name of person obtaining consent 
_________________________________ 
 
___________ 
 
 
Signature of person obtaining consent 
                      Date
CCF IRB #: 15-168
Approval Date: 2/13/2018
Expiration Date: 2/12/2019