Lymphoseek: Sentinel Lymph Node Biopsy Findings in Patients With Breast Cancer

• Sponsor: Kettering Health Network (Other)
• Overall Status: Completed
• CT.gov ID: NCT02287675
• Collaborator: (none)
• Enrollment: 40
• Location: 1
• Arms: 2
• Actual Duration (Months): 31.4
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

To compare the kinetics and efficacy of two functionally different diagnostic agents, Lymphoseek (CD206 receptor targeted) and 99mTc-Sulfur Colloid (SC) (Sulfur Colloid non-specific mapping agent) in intraoperative lymphatic mapping (ILM) and Sentinel Lymph Node Biopsy (SLNB).

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Lymphoseek; Drug: Sulfur Colloid	Phase 4

Detailed Description

Single center, blinded, randomized, parallel-group, comparative study of Lymphoseek and 99mTc-SC in the preoperative and intraoperative detection of lymph nodes in subjects with known breast cancer. All subjects will receive a single dose of 50 μg Lymphoseek radiolabeled with 0.5 millicurie (mCi) Tc 99m or 0.5 mCi of 99mTc-SC. Subjects may also receive up to 1 mL of vital blue dye (VBD) as a companion ILM agent. All radio-labeled agents will be administered in a single intradermal injection.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Diagnostic
• Official Title: A Randomized, Double-Blinded Trial Comparing Lymphoseek and 99mTc-Sulfur Colloid With Regard to Pre-op Imaging and Imaging Drug Kinetics and Intra-op Lymphatic Mapping and Sentinel Lymph Node Biopsy Findings in Patients With Breast Cancer
• Actual Study Start Date: Jan 19, 2015
• Actual Primary Completion Date: Jan 23, 2017
• Actual Study Completion Date: Aug 31, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Lymphoseek Lymphoseek (technetium Tc 99m tilmanocept) Injection is indicated for lymphatic mapping with a hand-held gamma counter to assist in the localization of lymph nodes draining a primary tumor site in patients with breast cancer or melanoma and guiding sentinel lymph node biopsy using a hand-held gamma counter in patients with clinically node negative squamous cell carcinoma of the oral cavity.	Drug: Lymphoseek; Subjects will receive a single intradermal injection of Lymphoseek followed by SPECT imaging conducted in two phases: initial sequential planar imaging at 30 to 60 second intervals for the first 60 minutes and repeated at 90 minutes and 120 minutes, as indicated, for identification of the SLN followed by SPECT/CT for higher resolution imaging in transaxial, coronal, and sagittal planes. Subjects will then proceed to surgery for lymphatic mapping. Lymphoseek positivity will be based upon radioactivity counts derived from the application of the handheld gamma probe ex vivo. Tumor resection or mastectomy will be performed according to standard procedures.; Other Names: technetium Tc 99m tilmanocept
Active Comparator: Sulfur Colloid Technetium Tc 99m Sulfur Colloid Injection is a radioactive diagnostic agent indicated for use as follows: In adults, to assist in the: localization of lymph nodes draining a primary tumor in patients with breast cancer or malignant melanoma when used with a hand-held gamma counter. evaluation of peritoneovenous (LeVeen) shunt patency in adults.	Drug: Sulfur Colloid; Subjects will receive a single intradermal injection of 99mTc-SC followed by SPECT imaging conducted in two phases: initial sequential planar imaging at 30 to 60 second intervals for the first 60 minutes and repeated at 90 minutes and 120 minutes, as indicated, for identification of the SLN followed by SPECT/CT for higher resolution imaging in transaxial, coronal, and sagittal planes. Subjects will then proceed to surgery for lymphatic mapping. 99mTc-SC positivity will be based upon radioactivity counts derived from the application of the handheld gamma probe ex vivo. Tumor resection or mastectomy will be performed according to standard procedures.; Other Names: 99mTc-SC 99mTc-SC Sulfur Colloid

Outcome Measures

Primary Outcome Measures

1. Injection Site Clearance for Lymphoseek and 99mTc-Sulfur Colloid (SC). [2 hours]

   The rate of injection site clearance is the time from radiotracer injection to peak SLN radioactive level. Injection clearance rates will be determined by planar SPECT imaging and by SPECT/CT. Subjects will undergo standard sequential planar imaging at 30 to 60 seconds intervals until the sentinel lymph node is seen. Once a sentinel node is located, a SPECT/CT will be performed for higher resolution imaging in transaxial, coronal, and sagittal planes.

2. Sentinel Lymph Node Uptake Rate [2 hours]

   SLN uptake rates will be determined by planar SPECT (single-photon emission computerized tomography) imaging and by SPECT/CT (CT-computed tomography). Gamma counts will be obtained at the injection site by standard sequential planar imaging at 30 to 60 seconds intervals until the sentinel lymph node is seen. Once a sentinel node is located, a SPECT/CT will be performed for higher resolution imaging in transaxial, coronal, and sagittal planes. Figures showing the percent of peak activity in the node versus time will be constructed for each radiopharmaceutical. The average uptake rate for each radiopharmaceutical will be computed and the following test will be conducted using a two-sample t-test at a two-sided α=0.05 (one-sided α=0.025) level of significance: H0 (null hypothesis): µLS ≤ µSC vs. HA (alternative hypothesis): µLS > µSC, (µLS is the average SLN uptake rate of Lymphoseek) (µSC is the average SLN uptake rate of 99mTc Sulfur Colloid).

Secondary Outcome Measures

1. Number of Intraoperatively Detected Sentinel Lymph Nodes (SLNs) Identified [24 hours]

   To compare the number of intraoperatively detected SLNs identified by Lymphoseek and 99mTc-SC on an agent cohort basis

2. Ratio of Intraoperative Gamma Counts [24 hours]

   To compare differences in the ratio of intraoperative counts for Lymphoseek vs 99mTc-SC for the hottest harvested axillary Sentinel Lymph Node (SLN) relative to the primary intradermal injection site.

3. Patient Pain Tolerance [24 hours]

   To compare patient pain tolerance (i.e., patient's perceived level of discomfort) at the injection site for Lymphoseek vs 99mTc-SC using Wong-Baker pain rating scale of 0-10, where the higher the score, the higher the pain level.

4. Pathologic Assessment of the Excised Lymph Node(s) [24 hours]

   To compare pathologic assessment of the excised lymph node(s) to confirm the presence/absence of tumor metastases for Lymphoseek vs 99mTc-SC.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The subject must be female and 18 years of age or older.

• The subject must be a preoperative clinical Tis, T1, T2, T3, T4, as well as clinical N0 and clinical M0 breast cancer

• The subject must have a diagnosis of primary breast cancer.

• The subject must be a candidate for surgical intervention, either with lumpectomy and SLNB or with mastectomy and SLNB, as the treatment of her breast cancer.

• The subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of Grade 0 - 2

• The subject must provide written informed consent with Health Insurance Portability and Accountability Act (HIPAA) authorization before participating in the study

Exclusion Criteria:

• The subject has clinical or radiological or pathologic evidence of metastatic cancer, including any abnormal or enlarged clinical palpable lymph nodes or core biopsy/surgical biopsy/fine-needle-aspiration evidence of malignant cell within any lymph nodes.

• The subject has a known hypersensitivity to vital blue dye (VBD) in a case where vital blue dye was planned for use during SLNB.

• The subject has a positive pregnancy test or is lactating.

• The subject has had prior surgery to the indicated breast or axilla.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kettering Medical Center	Kettering	Ohio	United States	45429

Sponsors and Collaborators

• Kettering Health Network

Investigators

• Principal Investigator: Arash Kardan, MD, Kettering Health Network

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 29, 2015
• Informed Consent Form - May 1, 2015

More Information

Publications

None provided.

• Responsible Party: Kettering Health Network
• ClinicalTrials.gov Identifier: NCT02287675
• Other Study ID Numbers: KHNIC-P14-N001
• First Posted: Nov 11, 2014
• Last Update Posted: Jul 28, 2020
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Kettering Health Network: Sentinel Node
• Additional relevant MeSH terms: Breast Neoplasms

Study Results

Participant Flow

Arm/Group Title	Sulfur Colloid	Lymphoseek
Arm/Group Description	Technetium Tc 99m Sulfur Colloid Injection is a radioactive diagnostic agent indicated for use as follows: In adults, to assist in the: localization of lymph nodes draining a primary tumor in patients with breast cancer or malignant melanoma when used with a hand-held gamma counter. evaluation of peritoneovenous (LeVeen) shunt patency in adults.	Lymphoseek (technetium Tc 99m tilmanocept) Injection is indicated for lymphatic mapping with a hand-held gamma counter to assist in the localization of lymph nodes draining a primary tumor site in patients with breast cancer or melanoma and guiding sentinel lymph node biopsy using a hand-held gamma counter in patients with clinically node negative squamous cell carcinoma of the oral cavity.
Period Title: Overall Study
STARTED	22	18
COMPLETED	22	18
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Lymphoseek	Sulfur Colloid	Total
Arm/Group Description	Lymphoseek (technetium Tc 99m tilmanocept) Injection is indicated for lymphatic mapping with a hand-held gamma counter to assist in the localization of lymph nodes draining a primary tumor site in patients with breast cancer or melanoma and guiding sentinel lymph node biopsy using a hand-held gamma counter in patients with clinically node negative squamous cell carcinoma of the oral cavity.	Technetium Tc 99m Sulfur Colloid Injection is a radioactive diagnostic agent indicated for use as follows: In adults, to assist in the: localization of lymph nodes draining a primary tumor in patients with breast cancer or malignant melanoma when used with a hand-held gamma counter. evaluation of peritoneovenous (LeVeen) shunt patency in adults.	Total of all reporting groups
Overall Participants	18	22	40
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	13 72.2%	9 40.9%	22 55%
>=65 years	5 27.8%	13 59.1%	18 45%
Sex: Female, Male (Count of Participants)
Female	18 100%	22 100%	40 100%
Male	0 0%	0 0%	0 0%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Height (inches) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [inches]	63.97 (2.56)	65.02 (2.33)	64.55 (2.46)
Weight (pounds) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [pounds]	193.72 (38.9)	178.23 (41.45)	185.20 (40.57)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	33.33 (6.86)	29.61 (6.66)	31.28 (6.92)
Temperature (Degrees Fahrenheit) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Degrees Fahrenheit]	98.28 (0.52)	98.19 (0.66)	98.23 (0.59)
Systolic blood pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	138.22 (23.51)	138.86 (22.60)	138.58 (22.72)
Diastolic blood pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	80.61 (14.12)	78.91 (15.37)	79.68 (14.66)
pulse (beats per minute) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [beats per minute]	81.11 (10.86)	78.5 (11.31)	79.68 (11.04)
respiratory rate (breaths per minute) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [breaths per minute]	15.44 (1.54)	15.62 (2.04)	15.54 (1.80)

Outcome Measures

1. Primary Outcome

Title	Injection Site Clearance for Lymphoseek and 99mTc-Sulfur Colloid (SC).
Description	The rate of injection site clearance is the time from radiotracer injection to peak SLN radioactive level. Injection clearance rates will be determined by planar SPECT imaging and by SPECT/CT. Subjects will undergo standard sequential planar imaging at 30 to 60 seconds intervals until the sentinel lymph node is seen. Once a sentinel node is located, a SPECT/CT will be performed for higher resolution imaging in transaxial, coronal, and sagittal planes.
Time Frame	2 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lymphoseek	Sulfur Colloid
Arm/Group Description	Lymphoseek (technetium Tc 99m tilmanocept) Injection is indicated for lymphatic mapping with a hand-held gamma counter to assist in the localization of lymph nodes draining a primary tumor site in patients with breast cancer or melanoma and guiding sentinel lymph node biopsy using a hand-held gamma counter in patients with clinically node negative squamous cell carcinoma of the oral cavity.	Technetium Tc 99m Sulfur Colloid Injection is a radioactive diagnostic agent indicated for use as follows: In adults, to assist in the: localization of lymph nodes draining a primary tumor in patients with breast cancer or malignant melanoma when used with a hand-held gamma counter. evaluation of peritoneovenous (LeVeen) shunt patency in adults.
Measure Participants	18	22
Mean (Standard Deviation) [minutes]	1.78 (0.85)	0.045 (0.18)

2. Primary Outcome

Title	Sentinel Lymph Node Uptake Rate
Description	SLN uptake rates will be determined by planar SPECT (single-photon emission computerized tomography) imaging and by SPECT/CT (CT-computed tomography). Gamma counts will be obtained at the injection site by standard sequential planar imaging at 30 to 60 seconds intervals until the sentinel lymph node is seen. Once a sentinel node is located, a SPECT/CT will be performed for higher resolution imaging in transaxial, coronal, and sagittal planes. Figures showing the percent of peak activity in the node versus time will be constructed for each radiopharmaceutical. The average uptake rate for each radiopharmaceutical will be computed and the following test will be conducted using a two-sample t-test at a two-sided α=0.05 (one-sided α=0.025) level of significance: H0 (null hypothesis): µLS ≤ µSC vs. HA (alternative hypothesis): µLS > µSC, (µLS is the average SLN uptake rate of Lymphoseek) (µSC is the average SLN uptake rate of 99mTc Sulfur Colloid).
Time Frame	2 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lymphoseek	Sulfur Colloid
Arm/Group Description	Lymphoseek (technetium Tc 99m tilmanocept) Injection is indicated for lymphatic mapping with a hand-held gamma counter to assist in the localization of lymph nodes draining a primary tumor site in patients with breast cancer or melanoma and guiding sentinel lymph node biopsy using a hand-held gamma counter in patients with clinically node negative squamous cell carcinoma of the oral cavity.	Technetium Tc 99m Sulfur Colloid Injection is a radioactive diagnostic agent indicated for use as follows: In adults, to assist in the: localization of lymph nodes draining a primary tumor in patients with breast cancer or malignant melanoma when used with a hand-held gamma counter. evaluation of peritoneovenous (LeVeen) shunt patency in adults.
Measure Participants	18	22
Mean (Standard Deviation) [minutes]	59.28 (44.02)	86.46 (54.15)

3. Secondary Outcome

Title	Number of Intraoperatively Detected Sentinel Lymph Nodes (SLNs) Identified
Description	To compare the number of intraoperatively detected SLNs identified by Lymphoseek and 99mTc-SC on an agent cohort basis
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

Lymph Nodes Removed Intraoperative

Arm/Group Title	Lymphoseek	Sulfur Colloid
Arm/Group Description	Lymphoseek (technetium Tc 99m tilmanocept) Injection is indicated for lymphatic mapping with a hand-held gamma counter to assist in the localization of lymph nodes draining a primary tumor site in patients with breast cancer or melanoma and guiding sentinel lymph node biopsy using a hand-held gamma counter in patients with clinically node negative squamous cell carcinoma of the oral cavity.	Technetium Tc 99m Sulfur Colloid Injection is a radioactive diagnostic agent indicated for use as follows: In adults, to assist in the: localization of lymph nodes draining a primary tumor in patients with breast cancer or malignant melanoma when used with a hand-held gamma counter. evaluation of peritoneovenous (LeVeen) shunt patency in adults.
Measure Participants	18	22
Measure Lymph Nodes	28	32
Number [Lymph Nodes]	9	22

4. Secondary Outcome

Title	Ratio of Intraoperative Gamma Counts
Description	To compare differences in the ratio of intraoperative counts for Lymphoseek vs 99mTc-SC for the hottest harvested axillary Sentinel Lymph Node (SLN) relative to the primary intradermal injection site.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lymphoseek	Sulfur Colloid
Arm/Group Description	Lymphoseek (technetium Tc 99m tilmanocept) Injection is indicated for lymphatic mapping with a hand-held gamma counter to assist in the localization of lymph nodes draining a primary tumor site in patients with breast cancer or melanoma and guiding sentinel lymph node biopsy using a hand-held gamma counter in patients with clinically node negative squamous cell carcinoma of the oral cavity.	Technetium Tc 99m Sulfur Colloid Injection is a radioactive diagnostic agent indicated for use as follows: In adults, to assist in the: localization of lymph nodes draining a primary tumor in patients with breast cancer or malignant melanoma when used with a hand-held gamma counter. evaluation of peritoneovenous (LeVeen) shunt patency in adults.
Measure Participants	18	22
Mean (Standard Deviation) [Ratio]	0.1093 (0.0917)	0.2621 (0.6105)

5. Secondary Outcome

Title	Patient Pain Tolerance
Description	To compare patient pain tolerance (i.e., patient's perceived level of discomfort) at the injection site for Lymphoseek vs 99mTc-SC using Wong-Baker pain rating scale of 0-10, where the higher the score, the higher the pain level.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lymphoseek	Sulfur Colloid
Arm/Group Description	Lymphoseek (technetium Tc 99m tilmanocept) Injection is indicated for lymphatic mapping with a hand-held gamma counter to assist in the localization of lymph nodes draining a primary tumor site in patients with breast cancer or melanoma and guiding sentinel lymph node biopsy using a hand-held gamma counter in patients with clinically node negative squamous cell carcinoma of the oral cavity.	Technetium Tc 99m Sulfur Colloid Injection is a radioactive diagnostic agent indicated for use as follows: In adults, to assist in the: localization of lymph nodes draining a primary tumor in patients with breast cancer or malignant melanoma when used with a hand-held gamma counter. evaluation of peritoneovenous (LeVeen) shunt patency in adults.
Measure Participants	18	22
Mean (Standard Deviation) [score on a scale]	0.5278 (0.88238)	1.5682 (2.17286)

6. Secondary Outcome

Title	Pathologic Assessment of the Excised Lymph Node(s)
Description	To compare pathologic assessment of the excised lymph node(s) to confirm the presence/absence of tumor metastases for Lymphoseek vs 99mTc-SC.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

Intraoperative Lymph Nodes extracted with presence of radiotracer

Arm/Group Title	Lymphoseek	Sulfur Colloid
Arm/Group Description	Lymphoseek (technetium Tc 99m tilmanocept) Injection is indicated for lymphatic mapping with a hand-held gamma counter to assist in the localization of lymph nodes draining a primary tumor site in patients with breast cancer or melanoma and guiding sentinel lymph node biopsy using a hand-held gamma counter in patients with clinically node negative squamous cell carcinoma of the oral cavity.	Technetium Tc 99m Sulfur Colloid Injection is a radioactive diagnostic agent indicated for use as follows: In adults, to assist in the: localization of lymph nodes draining a primary tumor in patients with breast cancer or malignant melanoma when used with a hand-held gamma counter. evaluation of peritoneovenous (LeVeen) shunt patency in adults.
Measure Participants	18	22
Measure Lymph Nodes	9	22
Positive for tumor metastasis	2	0
Negative for tumor metastasis	7	22

Adverse Events

Time Frame	From screening through follow-up, up to 50 days
Arm/Group Title	Lymphoseek		Sulfur Colloid
Arm/Group Description	Lymphoseek (technetium Tc 99m tilmanocept) Injection is indicated for lymphatic mapping with a hand-held gamma counter to assist in the localization of lymph nodes draining a primary tumor site in patients with breast cancer or melanoma and guiding sentinel lymph node biopsy using a hand-held gamma counter in patients with clinically node negative squamous cell carcinoma of the oral cavity.		Technetium Tc 99m Sulfur Colloid Injection is a radioactive diagnostic agent indicated for use as follows: In adults, to assist in the: localization of lymph nodes draining a primary tumor in patients with breast cancer or malignant melanoma when used with a hand-held gamma counter. evaluation of peritoneovenous (LeVeen) shunt patency in adults.
All Cause Mortality
	Lymphoseek		Sulfur Colloid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/22 (0%)
Serious Adverse Events
	Lymphoseek		Sulfur Colloid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/22 (0%)
Other (Not Including Serious) Adverse Events
	Lymphoseek		Sulfur Colloid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/18 (11.1%)		3/22 (13.6%)
Gastrointestinal disorders
Nausea	1/18 (5.6%)	1	1/22 (4.5%)	1
Vomiting	1/18 (5.6%)	1	1/22 (4.5%)	1
Nervous system disorders
Intermittent headaches	0/18 (0%)	0	1/22 (4.5%)	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.