Lymph Node Mapping in Patients With Newly Diagnosed Endometrial Cancer Undergoing Surgery

• Sponsor: Case Comprehensive Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01939028
• Collaborator: (none)
• Enrollment: 58
• Location: 1
• Arm: 1
• Duration (Months): 39
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

This clinical trial studies lymph node mapping in patients with newly diagnosed endometrial cancer undergoing surgery. Lymph node mapping may help in planning surgery to remove endometrial cancer and affected lymph nodes.

Condition or Disease	Intervention/Treatment	Phase
Stage I Endometrial Carcinoma; Stage II Endometrial Carcinoma; Stage III Endometrial Carcinoma; Stage IV Endometrial Carcinoma	Procedure: lymph node mapping; Procedure: sentinel lymph node biopsy; Drug: isosulfan blue; Drug: indocyanine green solution; Procedure: therapeutic conventional surgery; Procedure: lymphadenectomy	N/A

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the detection rate, sensitivity, and negative predictive value of sentinel lymph node (SLN) biopsy in endometrial cancer patients.

SECONDARY OBJECTIVES:

1. To compare different surgical modalities (open procedures, minimally invasive procedures, and single-site technology) and different injectants (isosulfan blue and indocyanine green) for SLN biopsy.

2. To determine total operating room time (from the time the patient enters the room to the time the patient leaves the room) as well as console time (robotic)/operating time for minimally invasive procedures.

OUTLINE:

Patients undergo SLN mapping using isosulfan blue and/or indocyanine green solution injected directly into the cervix. Following SLN identification and biopsy, patients undergo hysterectomy, bilateral salpingo-oophorectomy, and/or complete pelvic lymphadenectomy. Patients expressing SLN positive for metastasis undergo para-aortic lymphadenectomy.

After completion of study treatment, patients are followed up at 2-4 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 58 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Sentinel Lymph Node Mapping for Endometrial Cancer
• Study Start Date: Jul 1, 2013
• Actual Primary Completion Date: Oct 1, 2016
• Actual Study Completion Date: Oct 1, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Diagnostic (SLN mapping, biopsy, surgery) Patients undergo SLN mapping using isosulfan blue and/or indocyanine green solution injected directly into the cervix. Following SLN identification and biopsy, patients undergo hysterectomy, bilateral salpingo-oophorectomy, and/or complete pelvic lymphadenectomy. Patients expressing SLN positive for metastasis undergo para-aortic lymphadenectomy.

Procedure: lymph node mapping; Undergo lymph node mapping using isosulfan blue and/or indocyanine green solution; Procedure: sentinel lymph node biopsy; Undergo SLN biopsy; Other Names: sentinel node biopsy ; Drug: isosulfan blue; Undergo lymph node mapping using isosulfan blue and/or indocyanine green solution; Other Names: Lymphazurin N-[4-[4-(diethylamino)phenyl] (2,5-disulfophenyl) Methylene]-2,5-cyclohexadien-1-ylidene]-N-ethylethanaminium hydroxide ; Drug: indocyanine green solution; Undergo lymph node mapping using isosulfan blue and/or indocyanine green solution; Other Names: IC-GREEN ICG solution ; Procedure: therapeutic conventional surgery; Undergo hysterectomy, bilateral salpingo-oophorectomy and/or complete pelvic lymphadenectomy; Procedure: lymphadenectomy; Undergo para-aortic lymphadenectomy

Outcome Measures

Primary Outcome Measures

1. Sensitivity of Sentential Lymph Node (SLN) Biopsy [Up to 4 weeks]

   Sensitivity estimated as the proportion of true positives among participants with lymph node metastases. Sensitivity Calculation= the number of patients with a positive SLN over those patients with a positive SLN plus those patients with a false negative lymph node.

2. Number of Participants in Whom a SLN is Detected [Up to 4 weeks]

   Detection Rate as defined by number of participants in whom a SLN is detected

3. Percent of Hemipelvises Identified With SLN [Up to 4 weeks]

   Detection rate, as defined by percent of hemipelvises identified with SLN

4. Number of Participants With Sentinel Nodes Per Side of Pelvis [Up to 4 weeks]

   Detection rate, as defined as number of participants with a sentinel node found per side of pelvis

5. False Negative Rate as Defined as Proportion of Participants With False Negative Detection [Up to 4 weeks]

   False negative rate = 1-sensitivity or the number of patients with a false negative SLN over the number of patients with a positive SLN plus those with a false negative lymph node

6. Percent of True Positive SLN Identified With Surgical Modalities (Open Procedures, Minimally Invasive Procedures, and Single-site Technology) [Up to 4 weeks]

   The percent of true positive SLN identified with surgical modalities using pairwise comparisons for each surgical modality. Comparisons will be performed using two sample tests of proportions based on a normal approximation.

Secondary Outcome Measures

1. Percent of True Positive SLNs Using Isosulfan Blue and Indocyanine Green Solution [Up to 4 weeks]

   Percent of true positive SLN identified will be compared between injectants utilized using a two sample test of proportions based on a normal approximation. Comparisons will be performed using two sample tests of proportions based on a normal approximation.

2. Total Operating Room Time in Minutes [From the time the patient enters the room to the time the patient leaves the room, assessed up to 4 weeks]

   Total operating room time will be estimated as a mean with 95% confidence interval if the data have an approximately normal distribution. Otherwise, the median and a bootstrapped 95% confidence interval for the median will be reported. Similar summaries will be provided for the console time (robotic)/ operating time.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Women must have newly diagnosed histologically or cytologically confirmed endometrial cancer

• Women should have received no prior therapy for their disease

• Women who are planning to undergo hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy for the management of their endometrial cancer

• Women must have the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Women who are receiving any other investigational agents

• Women with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to isosulfan blue or indocyanine green or other agents used in this study

• Women with hypersensitivity to phenylmethane compounds, or a history of allergic reaction to iodides

• Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Women with a history of prior loop electrosurgical excision procedure (LEEP) or cone procedures performed on their cervix

• Women with a history of lymphedema, lymphoma, or lymphatic hyperplasia (Castleman disease)

• Women with a history of a prior malignancy

• Women may also be excluded at the discretion of their surgeon if he or she feels that the patient is not an appropriate candidate

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44195

Sponsors and Collaborators

• Case Comprehensive Cancer Center

Investigators

• Principal Investigator: Chad Michener, MD, Case Comprehensive Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 2, 2013
• Informed Consent Form - Jun 21, 2016

More Information

Publications

None provided.

• Responsible Party: Case Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT01939028
• Other Study ID Numbers: CASE9813; NCI-2013-01309
• First Posted: Sep 11, 2013
• Last Update Posted: Aug 27, 2020
• Last Verified: Aug 1, 2020

• Additional relevant MeSH terms: Carcinoma; Endometrial Neoplasms; Pharmaceutical Solutions

Study Results

Participant Flow

Arm/Group Title	Diagnostic (SLN Mapping, Biopsy, Surgery)
Arm/Group Description	Patients undergo SLN mapping using isosulfan blue and/or indocyanine green solution injected directly into the cervix. Following SLN identification and biopsy, patients undergo hysterectomy, bilateral salpingo-oophorectomy, and/or complete pelvic lymphadenectomy. Patients expressing SLN positive for metastasis undergo para-aortic lymphadenectomy. lymph node mapping: Undergo lymph node mapping using isosulfan blue and/or indocyanine green solution sentinel lymph node biopsy: Undergo SLN biopsy isosulfan blue: Undergo lymph node mapping using isosulfan blue and/or indocyanine green solution indocyanine green solution: Undergo lymph node mapping using isosulfan blue and/or indocyanine green solution therapeutic conventional surgery: Undergo hysterectomy, bilateral salpingo-oophorectomy and/or complete pelvic lymphadenectomy lymphadenectomy: Undergo para-aortic lymphadenectomy
Period Title: Overall Study
STARTED	58
COMPLETED	46
NOT COMPLETED	12

Baseline Characteristics

Arm/Group Title	Diagnostic (SLN Mapping, Biopsy, Surgery)
Arm/Group Description	Patients undergo SLN mapping using isosulfan blue and/or indocyanine green solution injected directly into the cervix. Following SLN identification and biopsy, patients undergo hysterectomy, bilateral salpingo-oophorectomy, and/or complete pelvic lymphadenectomy. Patients expressing SLN positive for metastasis undergo para-aortic lymphadenectomy.
Overall Participants	46
Age, Customized (Count of Participants)
20-29 years	1 2.2%
30-39 years	0 0%
40-49 years	4 8.7%
50-59 years	7 15.2%
60-69 years	21 45.7%
70-79 years	12 26.1%
80-89 years	1 2.2%
Sex: Female, Male (Count of Participants)
Female	46 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	46 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 8.7%
White	42 91.3%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	46 100%

Outcome Measures

1. Primary Outcome

Title	Sensitivity of Sentential Lymph Node (SLN) Biopsy
Description	Sensitivity estimated as the proportion of true positives among participants with lymph node metastases. Sensitivity Calculation= the number of patients with a positive SLN over those patients with a positive SLN plus those patients with a false negative lymph node.
Time Frame	Up to 4 weeks

Outcome Measure Data

Analysis Population Description

Participants with with lymph node metastases

Arm/Group Title	Diagnostic (SLN Mapping, Biopsy, Surgery)
Arm/Group Description	Participants undergo SLN mapping using isosulfan blue and/or indocyanine green solution injected directly into the cervix. Following SLN identification and biopsy, patients undergo hysterectomy, bilateral salpingo-oophorectomy, and/or complete pelvic lymphadenectomy. Patients expressing SLN positive for metastasis undergo para-aortic lymphadenectomy.
Measure Participants	13
Number [percent]	100

2. Primary Outcome

Title	Number of Participants in Whom a SLN is Detected
Description	Detection Rate as defined by number of participants in whom a SLN is detected
Time Frame	Up to 4 weeks

Outcome Measure Data

Analysis Population Description

Participants who completed study

Arm/Group Title	Diagnostic (SLN Mapping, Biopsy, Surgery)
Arm/Group Description	Participants undergo SLN mapping using isosulfan blue and/or indocyanine green solution injected directly into the cervix. Following SLN identification and biopsy, patients undergo hysterectomy, bilateral salpingo-oophorectomy, and/or complete pelvic lymphadenectomy. Patients expressing SLN positive for metastasis undergo para-aortic lymphadenectomy.
Measure Participants	46
Count of Participants [Participants]	44 95.7%

3. Primary Outcome

Title	Percent of Hemipelvises Identified With SLN
Description	Detection rate, as defined by percent of hemipelvises identified with SLN
Time Frame	Up to 4 weeks

Outcome Measure Data

Analysis Population Description

Participants who completed study

Arm/Group Title	Diagnostic (SLN Mapping, Biopsy, Surgery)
Arm/Group Description	Participants undergo SLN mapping using isosulfan blue and/or indocyanine green solution injected directly into the cervix. Following SLN identification and biopsy, patients undergo hysterectomy, bilateral salpingo-oophorectomy, and/or complete pelvic lymphadenectomy. Patients expressing SLN positive for metastasis undergo para-aortic lymphadenectomy.
Measure Participants	46
Number [Percent of Hemipelvises]	81.5

4. Primary Outcome

Title	Number of Participants With Sentinel Nodes Per Side of Pelvis
Description	Detection rate, as defined as number of participants with a sentinel node found per side of pelvis
Time Frame	Up to 4 weeks

Outcome Measure Data

Analysis Population Description

Participants who completed study

Arm/Group Title	Diagnostic (SLN Mapping, Biopsy, Surgery)
Arm/Group Description	Participants undergo SLN mapping using isosulfan blue and/or indocyanine green solution injected directly into the cervix. Following SLN identification and biopsy, patients undergo hysterectomy, bilateral salpingo-oophorectomy, and/or complete pelvic lymphadenectomy. Patients expressing SLN positive for metastasis undergo para-aortic lymphadenectomy.
Measure Participants	46
Right side of pelvis	39 84.8%
Left side of pelvis	36 78.3%

5. Primary Outcome

Title	False Negative Rate as Defined as Proportion of Participants With False Negative Detection
Description	False negative rate = 1-sensitivity or the number of patients with a false negative SLN over the number of patients with a positive SLN plus those with a false negative lymph node
Time Frame	Up to 4 weeks

Outcome Measure Data

Analysis Population Description

Participants who completed study

Arm/Group Title	Diagnostic (SLN Mapping, Biopsy, Surgery)
Arm/Group Description	Participants undergo SLN mapping using isosulfan blue and/or indocyanine green solution injected directly into the cervix. Following SLN identification and biopsy, patients undergo hysterectomy, bilateral salpingo-oophorectomy, and/or complete pelvic lymphadenectomy. Patients expressing SLN positive for metastasis undergo para-aortic lymphadenectomy.
Measure Participants	46
Number [Proportion of participants]	0 0%

6. Primary Outcome

Title	Percent of True Positive SLN Identified With Surgical Modalities (Open Procedures, Minimally Invasive Procedures, and Single-site Technology)
Description	The percent of true positive SLN identified with surgical modalities using pairwise comparisons for each surgical modality. Comparisons will be performed using two sample tests of proportions based on a normal approximation.
Time Frame	Up to 4 weeks

Outcome Measure Data

Analysis Population Description

Participants who completed study

Arm/Group Title	Diagnostic (SLN Mapping, Biopsy, Surgery)
Arm/Group Description	Participants undergo SLN mapping using isosulfan blue and/or indocyanine green solution injected directly into the cervix. Following SLN identification and biopsy, patients undergo hysterectomy, bilateral salpingo-oophorectomy, and/or complete pelvic lymphadenectomy. Patients expressing SLN positive for metastasis undergo para-aortic lymphadenectomy.
Measure Participants	46
Laparoscopy	83.3
Robot	86.4
Single port	79.0

7. Secondary Outcome

Title	Percent of True Positive SLNs Using Isosulfan Blue and Indocyanine Green Solution
Description	Percent of true positive SLN identified will be compared between injectants utilized using a two sample test of proportions based on a normal approximation. Comparisons will be performed using two sample tests of proportions based on a normal approximation.
Time Frame	Up to 4 weeks

Outcome Measure Data

Analysis Population Description

Participants who completed study

Arm/Group Title	Diagnostic (SLN Mapping, Biopsy, Surgery)
Arm/Group Description	Participants undergo SLN mapping using isosulfan blue and/or indocyanine green solution injected directly into the cervix. Following SLN identification and biopsy, patients undergo hysterectomy, bilateral salpingo-oophorectomy, and/or complete pelvic lymphadenectomy. Patients expressing SLN positive for metastasis undergo para-aortic lymphadenectomy.
Measure Participants	46
indocyanine green	86.54
Blue dye	75

8. Secondary Outcome

Title	Total Operating Room Time in Minutes
Description	Total operating room time will be estimated as a mean with 95% confidence interval if the data have an approximately normal distribution. Otherwise, the median and a bootstrapped 95% confidence interval for the median will be reported. Similar summaries will be provided for the console time (robotic)/ operating time.
Time Frame	From the time the patient enters the room to the time the patient leaves the room, assessed up to 4 weeks

Outcome Measure Data

Analysis Population Description

Participants who completed study

Arm/Group Title	Diagnostic (SLN Mapping, Biopsy, Surgery)
Arm/Group Description	Participants undergo SLN mapping using isosulfan blue and/or indocyanine green solution injected directly into the cervix. Following SLN identification and biopsy, patients undergo hysterectomy, bilateral salpingo-oophorectomy, and/or complete pelvic lymphadenectomy. Patients expressing SLN positive for metastasis undergo para-aortic lymphadenectomy.
Measure Participants	46
Median (95% Confidence Interval) [minutes]	158.5

Adverse Events

Time Frame	Up to 30 days from last treatment dose
Arm/Group Title	Diagnostic (SLN Mapping, Biopsy, Surgery)
Arm/Group Description	Patients undergo SLN mapping using isosulfan blue and/or indocyanine green solution injected directly into the cervix. Following SLN identification and biopsy, patients undergo hysterectomy, bilateral salpingo-oophorectomy, and/or complete pelvic lymphadenectomy. Patients expressing SLN positive for metastasis undergo para-aortic lymphadenectomy.
All Cause Mortality
	Diagnostic (SLN Mapping, Biopsy, Surgery)
	Affected / at Risk (%)	# Events
Total	0/58 (0%)
Serious Adverse Events
	Diagnostic (SLN Mapping, Biopsy, Surgery)
	Affected / at Risk (%)	# Events
Total	0/58 (0%)
Other (Not Including Serious) Adverse Events
	Diagnostic (SLN Mapping, Biopsy, Surgery)
	Affected / at Risk (%)	# Events
Total	1/58 (1.7%)
Cardiac disorders
New onset atrial fibrillation	1/58 (1.7%)	1

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.