Trial of Lymphoseek in Intraoperative Localization of Lymph Nodes in Breast Cancer and Melanoma
Data from this pivotal clinical trial will be used to support a marketing application (i.e., NDA) for Navidea's Lymphoseek for use in intraoperative localization of lymph tissue (nodes) in the lymphatic pathway draining the primary site of a tumor.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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:||April 2008|
|Study Completion Date:||July 2009|
|Primary Completion Date:||June 2009 (Final data collection date for primary outcome measure)|
|Experimental: Lymphoseek, Lymphatic mapping, Injection||
Breast Cancer: Intradermal admin of Lymphoseek: Inject 0.2-0.4 mL in multiple divided injections or a single injection overlying the intact primary tumor or excision biopsy site OR periareolar administration of Lymphoseek: Inject 0.2-.04 mL in multiple divided doses at the margin of the areola OR subareolar administration of Lymphoseek: Inject 0.2-0.4 in multiple divided injections or a single injection in subareolar area as a subcutaneous injection OR peritumor administration of Lymphoseek: Inject 2.0-4.0 mL in multiple divided injections, intraparenchemally surrounding the tumor or biopsy cavity. For melanoma pts intradermal administration of Lymphoseek: Inject 0.2-0.4 mL in multiple divided injections or a single injection overlying the intact primary tumor or excision biopsy site.
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 (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.
Lymphatic mapping 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-99m-labeled diethylenetriamine pentaacetic 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.
|United States, Alabama|
|Barbara Michna, M.D|
|Alexander City, Alabama, United States, 35010|
|Helen Krontiras, M.D.|
|Birmingham, Alabama, United States, 35294|
|United States, California|
|Anne Wallace, M.D.|
|La Jolla, California, United States, 92093|
|Ken Deck, M.D.|
|Laguna Hills, California, United States, 92653|
|Steve Martinez, M.D.|
|Sacramento, California, United States, 95817|
|Mark Faries, M.D.|
|Santa Monica, California, United States, 90404|
|United States, Florida|
|Eli Avisar, M.D.|
|Miami, Florida, United States, 33101|
|Vernon Sondak, M.D.|
|Tampa, Florida, United States, 33612|
|Charles Cox, M.D.|
|Tampa, Florida, United States, 33612|
|United States, Ohio|
|Julian Kim, M.D.|
|Cleveland, Ohio, United States, 44106|
|Bruce Averbook, M.D|
|Cleveland, Ohio, United States, 44109|
|Stephen Povoski, M.D.|
|Columbus, Ohio, United States, 43210|
|United States, Pennsylvania|
|Thomas Frazier, M.D.|
|Bryn Mawr, Pennsylvania, United States, 19010|
|Ned Carp, M.D.|
|Philadelphia, Pennsylvania, United States, 19096|
|Schlomo Schneebaum, M.D.|
|Tel Aviv, Israel, 64239|
|Study Director:||Richard Orahood, M.D.||Navidea Biopharmaceuticals|