Detection of SLN in Patients With Endometrial Cancer Undergoing Robotic Assisted Staging: Comparison of ISB and ICG

• Sponsor: AdventHealth (Other)
• Overall Status: Completed
• CT.gov ID: NCT02068820
• Collaborator: (none)
• Enrollment: 200
• Location: 1
• Arms: 2
• Duration (Months): 28
• Patients Per Site Per Month: 7.1

Study Details

Study Description

Brief Summary

The investigators hypothesis is that if sensitivity and specificity are found to be significantly higher than the current reports with Technesium-99 and ISB colorimetric dye, SLN biopsies might allow omission of full lymphadenectomy in lower-risk cases, thereby limiting peri-operative morbidity. SLN biopsies might also improve the detection of metastatic disease, essentially lowering the recognized false-negative rate of standard lymphadenectomy analyzed by routine H&E pathologic analysis.

Condition or Disease	Intervention/Treatment	Phase
Endometrial Cancer	Device: ISB dye and standard white light imaging; Device: ICG dye and FireFly fluorescence imaging	N/A

Detailed Description

The study objective is to compare two sentinel lymph node detection technologies [fluorescence imaging and Indocyanine Green (ICG) dye verses standard laparoscopic colorimetric analysis using Isosulfan Blue (ISB) dye] for sensitivity and specificity of detecting metastatic disease in pelvic lymph nodes of women with endometrial cancer undergoing robotic-assisted laparoscopic hysterectomy and lymphadenectomy. The following three specific aims would be addressed in this research proposal:

Specific Aim 1: To determine the ability of mapping bilaterally pelvic SLN in women with endometrial cancer undergoing robotic-assisted laparoscopic staging comparing two different methods (i.e., comparing the combination of colorimetric analysis-ISB dye + fluorescence imaging-ICG dye vs. colorimetric analysis-ISB dye alone).

Specific Aim 2: To estimate the negative predictive value (NPV) of pelvic SLN in endometrial cancer with respect to predicting nodal metastasis.

Specific Aim 3: To evaluate the ability of sentinel lymph nodes to increase the detection of metastatic disease through ultra-sectioning and immuno-histochemical (IHC) staining by comparing IHC results and standard hematoxylin and eosin (H&E) results.

Study Design

• Study Type: Interventional
• Actual Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Detection of Sentinel Lymph Nodes in Patients With Endometrial Cancer Undergoing Robotic-Assisted Staging: Comparison of Isosulfan Blue (ISB) and Indocyanine Green Dyes (ICG) With Fluorescence Imaging
• Study Start Date: Sep 1, 2012
• Actual Primary Completion Date: Jan 1, 2015
• Actual Study Completion Date: Jan 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: ISB dye, standard white light SLN mapping utilizing da Vinci surgical system with Isosulfan Blue (ISB) dye and standard white light imaging.	Device: ISB dye and standard white light imaging; Sentinel lymph node mapping utilizing the da Vinci surgical system and ISB dye with standard white light imaging.; Other Names: Isosulfan Blue dye
Experimental: ICG dye, FireFly fluorescence imaging SLN mapping utilizing da Vinci surgical system with ISB dye and standard white light first, and then additionally, Indocyanine Green (ICG) dye and FireFly fluorescence imaging.	Device: ISB dye and standard white light imaging; Sentinel lymph node mapping utilizing the da Vinci surgical system and ISB dye with standard white light imaging.; Other Names: Isosulfan Blue dye ; Device: ICG dye and FireFly fluorescence imaging; Sentinel lymph node mapping utilizing the da Vinci surgical system with ICG dye and FireFly fluorescence imaging.; Other Names: Indocyanine green dye

Outcome Measures

Primary Outcome Measures

1. Number of Pelvic Sentinel Lymph Nodes (SLN) in Endometrial Cancer Patients Detected by Either ICG and/or ISB Dyes. [through 6 weeks post-operative]

Secondary Outcome Measures

1. Negative Predictive Value (NPV) of Pelvic SLN in Endometrial Cancer in Relation to the Number of Nodes With Metastasis. [through 6 weeks post-operative]

   The standard definition for negative predictive value was used to calculate NPV. There was one false negative SLN in this study, 39 true positive sentinel lymph nodes, and 140 negative pelvic metastatic patients. NPV = 140/141=99.3%

Other Outcome Measures

1. Number of Pelvic Sentinal Lymph Nodal Metastasis in Regard to Staining by Immunohistochemical (IHC) Staining in Comparison to Standard Hematoxylin and Eosin (H&E). [through 6 weeks post-operative]

   Of the 127 positive nodes with pathology information, the percentage of each type of node will be summarized by the staining method. Statistical testing of the individual staining methods compared to both will be computed using Chi-square test of independence.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. The patient must be ≥18 and ≤85 years of age.

2. The patient must be female.

3. The patient must be willing and able to provide informed consent.

4. The patient is willing and able to comply with the study protocol.

5. The patient has endometrial cancer and is scheduled for robotic hysterectomy and lymphadenectomy.

6. The patient agrees to follow-up examinations out to 6-weeks post-treatment

Exclusion Criteria:

1. The patient is not a candidate for robotic assisted hysterectomy and lymphadenectomy.

2. The patient has known or suspected allergies to iodine, ICG or ISB.

3. The patient has hepatic dysfunction confirmed by elevated liver function studies (i.e., hepatic enzyme SGOT, SGPT or Bilirubin > 2 x normal (based on reference values from the laboratory used by the patient)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Florida Hospital Gynecologic Oncology	Orlando	Florida	United States	32804

Sponsors and Collaborators

• AdventHealth

Investigators

• Principal Investigator: Robert Holloway, MD, Florida Hospital Gynecologic Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AdventHealth
• ClinicalTrials.gov Identifier: NCT02068820
• Other Study ID Numbers: SLN Mapping
• First Posted: Feb 21, 2014
• Last Update Posted: Sep 10, 2019
• Last Verified: Aug 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by AdventHealth: Sentinel lymph nodes; da Vinci; Firefly; Sentinel lymph node mapping; Fluorescence Imaging; SLN; SLN mapping
• Additional relevant MeSH terms: Endometrial Neoplasms; Fluorophosphate

Study Results

Participant Flow

Arm/Group Title	ISB Dye, Standard White Light	ICG Dye, FireFly Fluorescence Imaging
Arm/Group Description	SLN mapping utilizing da Vinci surgical system with Isosulfan Blue (ISB) dye and standard white light imaging. ISB dye and standard white light imaging: Sentinel lymph node mapping utilizing the da Vinci surgical system and ISB dye with standard white light imaging.	SLN mapping utilizing da Vinci surgical system with ISB dye and standard white light first, and then additionally, Indocyanine Green (ICG) dye and FireFly fluorescence imaging. ISB dye and standard white light imaging: Sentinel lymph node mapping utilizing the da Vinci surgical system and ISB dye with standard white light imaging. ICG dye and FireFly fluorescence imaging: Sentinel lymph node mapping utilizing the da Vinci surgical system with ICG dye and FireFly fluorescence imaging.
Period Title: Overall Study
STARTED	20	180
COMPLETED	20	180
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	ISB Dye, Standard White Light	ICG Dye, FireFly Fluorescence Imaging	Total
Arm/Group Description	SLN mapping utilizing da Vinci surgical system with Isosulfan Blue (ISB) dye and standard white light imaging. ISB dye and standard white light imaging: Sentinel lymph node mapping utilizing the da Vinci surgical system and ISB dye with standard white light imaging.	SLN mapping utilizing da Vinci surgical system with ISB dye and standard white light first, and then additionally, Indocyanine Green (ICG) dye and FireFly fluorescence imaging. ISB dye and standard white light imaging: Sentinel lymph node mapping utilizing the da Vinci surgical system and ISB dye with standard white light imaging. ICG dye and FireFly fluorescence imaging: Sentinel lymph node mapping utilizing the da Vinci surgical system with ICG dye and FireFly fluorescence imaging.	Total of all reporting groups
Overall Participants	20	180	200
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	7 35%	79 43.9%	86 43%
>=65 years	13 65%	101 56.1%	114 57%
Sex: Female, Male (Count of Participants)
Female	20 100%	180 100%	200 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	20 100%	180 100%	200 100%
Age (years) [Median (Standard Deviation) ]
Median (Standard Deviation) [years]	66.0 (6.7)	64.4 (8.6)	64.5 (8.4)

Outcome Measures

1. Primary Outcome

Title	Number of Pelvic Sentinel Lymph Nodes (SLN) in Endometrial Cancer Patients Detected by Either ICG and/or ISB Dyes.
Time Frame	through 6 weeks post-operative

Outcome Measure Data

Analysis Population Description

The ISB dye alone group (n=20) and the ICG group (n=180) are combined, because both groups received the ISB dye.

Arm/Group Title	ISB Dye, Standard White Light	ICG Dye, FireFly Fluorescence Imaging
Arm/Group Description	SLN mapping utilizing da Vinci surgical system with Isosulfan Blue (ISB) dye and standard white light imaging. ISB dye and standard white light imaging: Sentinel lymph node mapping utilizing the da Vinci surgical system and ISB dye with standard white light imaging.	SLN mapping utilizing da Vinci surgical system with ISB dye and standard white light first, and then additionally, Indocyanine Green (ICG) dye and FireFly fluorescence imaging. ISB dye and standard white light imaging: Sentinel lymph node mapping utilizing the da Vinci surgical system and ISB dye with standard white light imaging. ICG dye and FireFly fluorescence imaging: Sentinel lymph node mapping utilizing the da Vinci surgical system with ICG dye and FireFly fluorescence imaging.
Measure Participants	200	180
Mean (Standard Deviation) [nodes]	1.25 (.901)	2.03 (.720)

2. Secondary Outcome

Title	Negative Predictive Value (NPV) of Pelvic SLN in Endometrial Cancer in Relation to the Number of Nodes With Metastasis.
Description	The standard definition for negative predictive value was used to calculate NPV. There was one false negative SLN in this study, 39 true positive sentinel lymph nodes, and 140 negative pelvic metastatic patients. NPV = 140/141=99.3%
Time Frame	through 6 weeks post-operative

Outcome Measure Data

Analysis Population Description

Comparison of metastatic disease (yes or no) with ICG dye node detection (yes or no)

Arm/Group Title	ICG Negative	ICG Positive
Arm/Group Description	Experimental subjects with Indocyanine Green (ICG) negative test results	Experimental subjects with Indocyanine Green (ICG) positive test results
Measure Participants	141	39
Metastatic Disease	1 5%	39 21.7%
Non Metastatic Disease	140 700%	0 0%

3. Other Pre-specified Outcome

Title	Number of Pelvic Sentinal Lymph Nodal Metastasis in Regard to Staining by Immunohistochemical (IHC) Staining in Comparison to Standard Hematoxylin and Eosin (H&E).
Description	Of the 127 positive nodes with pathology information, the percentage of each type of node will be summarized by the staining method. Statistical testing of the individual staining methods compared to both will be computed using Chi-square test of independence.
Time Frame	through 6 weeks post-operative

Outcome Measure Data

Analysis Population Description

These are positive sentinel lymph nodes

Arm/Group Title	IHC Only	H&E Only	Both IHC and H&E
Arm/Group Description	Positive node identified with IHC dye only	Positive node identified with H&E only	Positive node identified with both IHC and H&E dye
Measure Participants	NA	NA	NA
Measure Nodes	18	91	18
Sentinel Nodes	16	31	16
Pelvic Nodes Only	1	36	2
Aortic	1	14	0
Infrarenal	0	10	0

Adverse Events

Time Frame	Post-op follow up 6 weeks
Arm/Group Title	ISB Only Adverse Events		ICG Adverse Events
Arm/Group Description	ISB only Adverse Events categories reported during post-op follow up 6 weeks		ICG Adverse Events categories reported during post-op follow up 6 weeks
All Cause Mortality
	ISB Only Adverse Events		ICG Adverse Events
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	ISB Only Adverse Events		ICG Adverse Events
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/180 (0%)
Other (Not Including Serious) Adverse Events
	ISB Only Adverse Events		ICG Adverse Events
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/20 (25%)		29/180 (16.1%)
Blood and lymphatic system disorders
Blood and lymphatic system complications	2/20 (10%)		8/180 (4.4%)
Cardiac disorders
Cardiac complications	1/20 (5%)		3/180 (1.7%)
Gastrointestinal disorders
Gastrointestinal complications	0/20 (0%)		3/180 (1.7%)
General disorders
General disorders and administration site conditions	1/20 (5%)		4/180 (2.2%)
Renal and urinary disorders
Renal and urinary complications	0/20 (0%)		4/180 (2.2%)
Reproductive system and breast disorders
Reproductive system complications	2/20 (10%)		7/180 (3.9%)
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic, and pulmonary complications	0/20 (0%)		3/180 (1.7%)
Skin and subcutaneous tissue disorders
Cellulitis	1/20 (5%)		5/180 (2.8%)
Surgical and medical procedures
Wound complications	2/20 (10%)		1/180 (0.6%)
Vascular disorders
Vascular complications	1/20 (5%)		0/180 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.