Clinical trial NCT00671918
Conditions: Breast Cancer Melanoma
Keywords: breast cancer lymph nodes melanoma surgery
Sponsor: Navidea Biopharmaceuticals
Start date: 2008-04-01; Completion date: 2009-07-01
Enrollment: 186 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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.

Detailed description:
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.

Arms: arm 1: None
Interventions: intervention 1: Lymphoseek
Intervention descriptions: intervention 1: 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.

Protocol documents: