Rhabdomyosarcoma, Melanoma
Conditions
Brief summary
Open label, non-randomized, multi-center, within-subject comparative study to evaluate the tolerability and the diagnostic utility of Lymphoseek with optional comparison to VBD in pediatric subjects with melanoma, rhabdomyosarcoma, or other solid tumor. Subject age will range from neonatal through 17 years.
Interventions
A single dose of 0.5 mCi and 50 ug of Tc99m tilmanocept administered intradermally, peritumorally approximately 15 minutes to 8 hours before surgery
DRUGVital Blue Dye (optional)
A single dose 1-3 mL of vital blue dye (1%) administered intradermally at the start of or during surgery (optional, per institution's standard of care).
PROCEDURELymph Node Mapping
Intraoperative lymph node mapping will occur 15 minutes to 8 hours after Tc99m tilmanocept injection
Sponsors
Cardinal Health 414, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 17 Years
Healthy volunteers
No
Inclusion criteria
* The subject's parent(s)/legal guardian(s) understand(s) and voluntarily signed an informed consent document prior to any study-related assessments/procedures being conducted. Where locally applicable, the subject also understands and voluntarily provides his/her assent prior to any study-related assessments/procedures being conducted * Subject has been diagnosed with melanoma, rhabdomyosarcoma, or other tumor where tumor resection or biopsy is planned and lymph node mapping is appropriate * The subject is clinically node negative (cN0) at the time of screening * Age \< 18 years * Male subjects of childbearing potential must be willing to use a condom during sexual intercourse and shall not father a child during the course of the study or will practice complete abstinence while on study * Female subjects of childbearing potential must agree to the use of two physician-approved contraceptive methods simultaneously or practice complete abstinence while on study
Exclusion criteria
* The subject has had preoperative radiation therapy * Has had previous surgery or radiation to node basins that would be involved in the intraoperative lymph node mapping (ILM) procedure * Has a known allergy to dextran or VBD (if intended to be used) * Has a history of alcohol abuse or alcohol dependency in the 3 years before study entry, or is an alcoholic or drug addict, as determined by the investigator * Before the administration of Lymphoseek, has received any radiopharmaceutical within 7 radioactive half-lives of that radiopharmaceutical
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Number of Lymph Nodes Identified Intraoperatively Per Subject | 1 Day | — |
| Subject Localization Rates | 1 Day | The proportion of subjects with Lymphoseek-identified lymph nodes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Number of Lymph Nodes Identified Preoperatively Using SPECT or SPECT/CT Per Subject | 1 Day | — |
| Agreement of the Number of Nodes Identified by Preoperative SPECT or SPECT/CT to Intraoperative Localization | 1 Day | Average difference in number of LNs identified preoperatively with SPECT/CR and number of LNs identified intraoperatively per subject |
| Upstaging | 1 Day | The proportion of patients with pathology-positive lymph nodes who had at least one pathology-positive lymph node that was identified by Lymphoseek and had no other pathology-positive lymph nodes (i.e., identified by any other method) |
| Nodal False Negative Rate for Nodes Identified | 1 Day | The number of pathology-positive lymph nodes that were missed intraoperatively by mapping agent divided by the total number of pathology-positive lymph nodes for that mapping agent. Population is all subjects with pathology-positive nodes. False negative rate represents the failure rate of the mapping agent to identify sentinel lymph nodes. |
| Proportion of Subjects Who Underwent Preoperative SPECT or SPECT/CT | 1 Day | — |
| Nodal Agreement of Central Pathology Assessment With Local Pathology Assessment of the Excised Lymph Node(s) to Confirm the Presence/Absence of Tumor Metastases | 1 Day | Number of nodes whose local and central pathology results agree divided by the number of nodes with nonmissing local and central pathology results |
| Change in Subject Nodal Staging Before and After Surgery Based Upon Nodes Identified | 1 Day | Change in subject nodal staging was assessed via shift tables to show the number of subjects with each combination of presurgery and postsurgery nodal staging. Presurgery staging was based on standard-of-care clinical assessment. Postsurgery staging was based on the pathology results of the nodes identified. |
| Number of Changes in Postsurgical Treatment Plan in Relation to Nodes Identified by Lymphoseek | 1 Day | Changes to postsurgical treatment plan will be compared to baseline treatment plan. |
| Nodal Sensitivity | 1 Day | The number of pathology-positive lymph nodes that were identified intraoperatively by mapping agent divided by the total number of pathology-positive lymph nodes for that mapping agent. Population is all subjects with pathology-positive nodes. Sensitivity rate represents the success rate of the mapping agent to identify sentinel lymph nodes. |
| Proportion of Subjects With a Lymph Node Identified Preoperatively Using SPECT or SPECT/CT | 1 day | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tc99m Tilmanocept and Vital Blue Dye (Optional) 0.5 mCi, 50 ug of Tc99m tilmanocept single administration. Optionally, 1-3 mL of vital blue dye, single administration (per institution's standard of care).
Tc99m tilmanocept: A single dose of 0.5 mCi and 50 ug of Tc99m tilmanocept administered intradermally, peritumorally approximately 15 minutes to 8 hours before surgery
Vital Blue Dye (optional): A single dose 1-3 mL of vital blue dye (1%) administered intradermally at the start of or during surgery (optional, per institution's standard of care).
Lymph Node Mapping: Intraoperative lymph node mapping will occur 15 minutes to 8 hours after Tc99m tilmanocept injection | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Tc99m Tilmanocept and Vital Blue Dye (Optional) |
|---|---|
| Age, Continuous | 11.6 years STANDARD_DEVIATION 4.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 21 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 8 Participants |
| Tumor type Melanoma | 5 Participants |
| Tumor type Other solid tumors | 14 Participants |
| Tumor type Rhabdomyosarcoma | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 23 |
| other Total, other adverse events | 5 / 23 |
| serious Total, serious adverse events | 3 / 23 |
Outcome results
Primary
Average Number of Lymph Nodes Identified Intraoperatively Per Subject
Time frame: 1 Day
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Tc99m Tilmanocept and Vital Blue Dye (Optional) | Average Number of Lymph Nodes Identified Intraoperatively Per Subject | 3.30 nodes per subject |
Primary
Subject Localization Rates
The proportion of subjects with Lymphoseek-identified lymph nodes
Time frame: 1 Day
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tc99m Tilmanocept and Vital Blue Dye (Optional) | Subject Localization Rates | 22 Participants |
Secondary
Agreement of the Number of Nodes Identified by Preoperative SPECT or SPECT/CT to Intraoperative Localization
Average difference in number of LNs identified preoperatively with SPECT/CR and number of LNs identified intraoperatively per subject
Time frame: 1 Day
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Tc99m Tilmanocept and Vital Blue Dye (Optional) | Agreement of the Number of Nodes Identified by Preoperative SPECT or SPECT/CT to Intraoperative Localization | -0.86 nodes per subject |
Secondary
Average Number of Lymph Nodes Identified Preoperatively Using SPECT or SPECT/CT Per Subject
Time frame: 1 Day
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Tc99m Tilmanocept and Vital Blue Dye (Optional) | Average Number of Lymph Nodes Identified Preoperatively Using SPECT or SPECT/CT Per Subject | 2.75 nodes per subject |
Secondary
Change in Subject Nodal Staging Before and After Surgery Based Upon Nodes Identified
Change in subject nodal staging was assessed via shift tables to show the number of subjects with each combination of presurgery and postsurgery nodal staging. Presurgery staging was based on standard-of-care clinical assessment. Postsurgery staging was based on the pathology results of the nodes identified.
Time frame: 1 Day
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tc99m Tilmanocept and Vital Blue Dye (Optional) | Change in Subject Nodal Staging Before and After Surgery Based Upon Nodes Identified | 3 Participants |
Secondary
Nodal Agreement of Central Pathology Assessment With Local Pathology Assessment of the Excised Lymph Node(s) to Confirm the Presence/Absence of Tumor Metastases
Number of nodes whose local and central pathology results agree divided by the number of nodes with nonmissing local and central pathology results
Time frame: 1 Day
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Tc99m Tilmanocept and Vital Blue Dye (Optional) | Nodal Agreement of Central Pathology Assessment With Local Pathology Assessment of the Excised Lymph Node(s) to Confirm the Presence/Absence of Tumor Metastases | 57 Nodes with nonmissing pathology |
Secondary
Nodal False Negative Rate for Nodes Identified
The number of pathology-positive lymph nodes that were missed intraoperatively by mapping agent divided by the total number of pathology-positive lymph nodes for that mapping agent. Population is all subjects with pathology-positive nodes. False negative rate represents the failure rate of the mapping agent to identify sentinel lymph nodes.
Time frame: 1 Day
Population: Subjects with pathology-positive nodes
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tc99m Tilmanocept and Vital Blue Dye (Optional) | Nodal False Negative Rate for Nodes Identified | 0 proportion |
Secondary
Nodal Sensitivity
The number of pathology-positive lymph nodes that were identified intraoperatively by mapping agent divided by the total number of pathology-positive lymph nodes for that mapping agent. Population is all subjects with pathology-positive nodes. Sensitivity rate represents the success rate of the mapping agent to identify sentinel lymph nodes.
Time frame: 1 Day
Population: Subjects with pathology-positive nodes
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tc99m Tilmanocept and Vital Blue Dye (Optional) | Nodal Sensitivity | 1.00 proportion |
Secondary
Number of Changes in Postsurgical Treatment Plan in Relation to Nodes Identified by Lymphoseek
Changes to postsurgical treatment plan will be compared to baseline treatment plan.
Time frame: 1 Day
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tc99m Tilmanocept and Vital Blue Dye (Optional) | Number of Changes in Postsurgical Treatment Plan in Relation to Nodes Identified by Lymphoseek | 2 Participants |
Secondary
Proportion of Subjects Who Underwent Preoperative SPECT or SPECT/CT
Time frame: 1 Day
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tc99m Tilmanocept and Vital Blue Dye (Optional) | Proportion of Subjects Who Underwent Preoperative SPECT or SPECT/CT | 21 Participants |
Secondary
Proportion of Subjects With a Lymph Node Identified Preoperatively Using SPECT or SPECT/CT
Time frame: 1 day
Population: Number of subjects who underwent preoperative SPECT/CT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tc99m Tilmanocept and Vital Blue Dye (Optional) | Proportion of Subjects With a Lymph Node Identified Preoperatively Using SPECT or SPECT/CT | 20 Participants |
Secondary
Upstaging
The proportion of patients with pathology-positive lymph nodes who had at least one pathology-positive lymph node that was identified by Lymphoseek and had no other pathology-positive lymph nodes (i.e., identified by any other method)
Time frame: 1 Day
Population: Number of subjects with pathology-positive nodes
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tc99m Tilmanocept and Vital Blue Dye (Optional) | Upstaging | 2 Participants |