Breast and Melanoma Trial With Lymphoseek to Identify Lymph Nodes
Data from this pivotal clinical trial will be used to support a marketing application (i.e., NDA) of Navidea's Lymphoseek for use in anatomical delineation of lymphoid tissue (nodes) in the lymphatic pathway draining the primary site of a tumor.
Multicenter, open-label, within-patient comparative study of Lymphoseek and vital blue dye in the detection of excised lymph nodes in patients with known melanoma and breast cancer. All patients will receive a single dose of 50 µg Lymphoseek radiolabeled with 0.5 or 2.0 mCi Tc 99m and vital blue dye.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
|Official Title:||A Phase 3, Prospective, Open-Label, Multicenter Comparison Study of Lymphoseek® and Vital Blue Dye as Lymphoid Tissue Targeting Agents in Patients With Known Melanoma or Breast Cancer Who Are Undergoing Lymph Node Mapping|
- Concordance of Blue Dye and Lymphoseek [ Time Frame: Surgery after injections of Lymphoseek and blue dye ] [ Designated as safety issue: No ]The proportion of lymph nodes detected intraoperatively by blue dye that were also detected by Lymphoseek.
- Reverse Concordance of Blue Dye and Lymphoseek [ Time Frame: Surgery after injections of Lymphoseek and blue dye ] [ Designated as safety issue: No ]The proportion of lymph nodes detected intraoperatively by Lymphoseek that were also detected by blue dye.
|Study Start Date:||June 2010|
|Study Completion Date:||April 2011|
|Primary Completion Date:||April 2011 (Final data collection date for primary outcome measure)|
|Experimental: Lymphoseek, Lymphatic mapping, Injection||
The total volume of Lymphoseek injection will be between 0.1 - 1.0 mL.
Other Name: technetium Tc 99m tilmanocept
In patients with primary melanoma and breast cancer, lymph node status is often a strong predictor of outcome and influences the course of treatment a patient may follow after surgery. In an effort to reduce the morbidity and costs of detection of lymph node metastases, surgical oncologists have developed a method by which the sentinel lymph node (SLN; the first node in a draining basin) is identified intraoperatively and removed. This technique, called sentinel node biopsy, has extremely high negative predictive values for melanoma metastases and breast cancer metastases. The two largest trials for melanoma, Morton, et al (2005) and Rossi, et al (2006), reported false negative rates of 6.3% and 14.7%, respectively. Morton, et al (2006), in perhaps the most mature trial reported to date, showed a false negative rate of 3.4%. There is growing evidence that sentinel node biopsy will have a significant impact on the management of melanoma. Sentinel node biopsy also has extremely high negative predictive values for breast cancer metastases; the false-negative rates range from 0% to 9%. There is growing evidence that sentinel node biopsy will have a significant impact on the management of breast cancer. Although the survival and local recurrence studies have yet to be completed, the technique has emerged into common practice.
Intraoperative lymphatic mapping (ILM) with a radiopharmaceutical is a nuclear medicine examination which identifies for the surgeon the first lymph node to receive lymphatic flow from the primary tumor site. This node is removed and analyzed for the presence of malignant cells. By locating the lymph node prior to surgery, a small incision can be used to remove the node and a smaller dissection can be employed. The high negative predictive value of the technique seems to provide an accurate staging procedure and may spare patients who are lymph node negative the morbidity of a complete lymph node dissection. Consequently, staging of melanoma by lymph node mapping and biopsy may be equivalent to regional node dissection without the attendant post surgical morbidity.
An ideal lymph node imaging agent would exhibit rapid clearance from the injection site, rapid uptake and high retention within the first draining lymph node, and low uptake by the remaining lymph nodes. The ideal agent would also have low radiation absorption; high biological safety; convenient, rapid, and stable technetium-99m labeling; and biochemical purity.
Lymphoseek (Technetium Tc 99m diethylenetriaminepentaacetic acid mannosyl dextran, [Tc 99m] DTPA Mannosyl Dextran) is a radiotracer that accumulates in lymphatic tissue by binding to a mannose binding protein that resides on the surface of dendritic cells and macrophages. Lymphoseek is a macromolecule consisting of multiple units of DTPA and mannose, each synthetically attached to a 10 kilodalton dextran backbone. The mannose acts as a substrate for the receptor, and the DTPA serves as a chelating agent for labeling with Tc 99m.
Lymphoseek has a diameter of about 5 nm, which is substantially smaller than current agents used for targeting lymphoid tissue. Lymphoseek's small diameter permits enhanced diffusion into lymph nodes and blood capillaries, resulting in a rapid injection site clearance. Upon entry into the blood, the agent binds to receptors in the liver or is filtered by the kidney and accumulates in the urinary bladder.
|United States, Alabama|
|University of Alabama, Birmingham|
|Birmingham, Alabama, United States, 35294|
|United States, California|
|UCSD Moores Cancer Center|
|La Jolla, California, United States, 92093|
|Califonia Pacific Medical Center|
|San Francisco, California, United States, 94115|
|John Wayne Cancer Institute|
|Santa Monica, California, United States, 90404|
|United States, Florida|
|H. Lee Moffitt Cancer Center|
|Tampa, Florida, United States, 33612|
|United States, Ohio|
|University Hospitals Cleveland|
|Cleveland, Ohio, United States, 44106|
|Breast Care Specialists|
|Columbus, Ohio, United States, 43081|
|The Ohio State University|
|Columbus, Ohio, United States, 43210|
|Study Director:||Simon A Blackburn||Navidea Biopharmaceuticals|