Breast Cancer
Conditions
Keywords
Sentinel Node
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).
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.
Interventions
DRUGLymphoseek
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.
DRUGSulfur 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.
Sponsors
Kettering Health Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 18 |
| 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. | 22 |
| Total | 40 |
Baseline characteristics
| Characteristic | Lymphoseek | Total | Sulfur Colloid |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 18 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 22 Participants | 9 Participants |
| BMI | 33.33 kg/m^2 STANDARD_DEVIATION 6.86 | 31.28 kg/m^2 STANDARD_DEVIATION 6.92 | 29.61 kg/m^2 STANDARD_DEVIATION 6.66 |
| Diastolic blood pressure | 80.61 mmHg STANDARD_DEVIATION 14.12 | 79.68 mmHg STANDARD_DEVIATION 14.66 | 78.91 mmHg STANDARD_DEVIATION 15.37 |
| Height | 63.97 inches STANDARD_DEVIATION 2.56 | 64.55 inches STANDARD_DEVIATION 2.46 | 65.02 inches STANDARD_DEVIATION 2.33 |
| pulse | 81.11 beats per minute STANDARD_DEVIATION 10.86 | 79.68 beats per minute STANDARD_DEVIATION 11.04 | 78.5 beats per minute STANDARD_DEVIATION 11.31 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| respiratory rate | 15.44 breaths per minute STANDARD_DEVIATION 1.54 | 15.54 breaths per minute STANDARD_DEVIATION 1.8 | 15.62 breaths per minute STANDARD_DEVIATION 2.04 |
| Sex: Female, Male Female | 18 Participants | 40 Participants | 22 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Systolic blood pressure | 138.22 mmHg STANDARD_DEVIATION 23.51 | 138.58 mmHg STANDARD_DEVIATION 22.72 | 138.86 mmHg STANDARD_DEVIATION 22.6 |
| Temperature | 98.28 Degrees Fahrenheit STANDARD_DEVIATION 0.52 | 98.23 Degrees Fahrenheit STANDARD_DEVIATION 0.59 | 98.19 Degrees Fahrenheit STANDARD_DEVIATION 0.66 |
| Weight | 193.72 pounds STANDARD_DEVIATION 38.9 | 185.20 pounds STANDARD_DEVIATION 40.57 | 178.23 pounds STANDARD_DEVIATION 41.45 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 22 |
| other Total, other adverse events | 2 / 18 | 3 / 22 |
| serious Total, serious adverse events | 0 / 18 | 0 / 22 |
Outcome results
Primary
Injection Site Clearance for Lymphoseek and 99mTc-Sulfur Colloid (SC).
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lymphoseek | Injection Site Clearance for Lymphoseek and 99mTc-Sulfur Colloid (SC). | 1.78 minutes | Standard Deviation 0.85 |
| Sulfur Colloid | Injection Site Clearance for Lymphoseek and 99mTc-Sulfur Colloid (SC). | 0.045 minutes | Standard Deviation 0.18 |
Primary
Sentinel Lymph Node Uptake Rate
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lymphoseek | Sentinel Lymph Node Uptake Rate | 59.28 minutes | Standard Deviation 44.02 |
| Sulfur Colloid | Sentinel Lymph Node Uptake Rate | 86.46 minutes | Standard Deviation 54.15 |
Secondary
Number of Intraoperatively Detected Sentinel Lymph Nodes (SLNs) Identified
To compare the number of intraoperatively detected SLNs identified by Lymphoseek and 99mTc-SC on an agent cohort basis
Time frame: 24 hours
Population: Lymph Nodes Removed Intraoperative
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lymphoseek | Number of Intraoperatively Detected Sentinel Lymph Nodes (SLNs) Identified | 9 Lymph Nodes |
| Sulfur Colloid | Number of Intraoperatively Detected Sentinel Lymph Nodes (SLNs) Identified | 22 Lymph Nodes |
Secondary
Pathologic Assessment of the Excised Lymph Node(s)
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
Population: Intraoperative Lymph Nodes extracted with presence of radiotracer
| Arm | Measure | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Lymphoseek | Pathologic Assessment of the Excised Lymph Node(s) | Positive for tumor metastasis | 2 Lymph Nodes |
| Lymphoseek | Pathologic Assessment of the Excised Lymph Node(s) | Negative for tumor metastasis | 7 Lymph Nodes |
| Sulfur Colloid | Pathologic Assessment of the Excised Lymph Node(s) | Positive for tumor metastasis | 0 Lymph Nodes |
| Sulfur Colloid | Pathologic Assessment of the Excised Lymph Node(s) | Negative for tumor metastasis | 22 Lymph Nodes |
Secondary
Patient Pain Tolerance
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lymphoseek | Patient Pain Tolerance | 0.5278 score on a scale | Standard Deviation 0.88238 |
| Sulfur Colloid | Patient Pain Tolerance | 1.5682 score on a scale | Standard Deviation 2.17286 |
Secondary
Ratio of Intraoperative Gamma Counts
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lymphoseek | Ratio of Intraoperative Gamma Counts | 0.1093 Ratio | Standard Deviation 0.0917 |
| Sulfur Colloid | Ratio of Intraoperative Gamma Counts | 0.2621 Ratio | Standard Deviation 0.6105 |