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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

Phase 3
18 Years
Not Enrolling
Breast Cancer, Melanoma

Thank you

Trial Information

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

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

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.

Inclusion Criteria:

1. The patient has provided written informed consent with HIPAA authorization.

2. The patient is a candidate for surgical intervention, with lymph node mapping being a
part of the surgical plan.

3. The patient is at least 18 years of age at the time of consent.

4. The patient has an ECOG performance status of Grade 0 - 2 (see Appendix A).

5. The patient has a clinical negative node status at the time of study entry (i.e.
T0-4, N0, M0, see Appendix D and E).

6. If of childbearing potential, the patient has a negative pregnancy test within 72
hours prior to administration of Lymphoseek, has been surgically sterilized, or has
been postmenopausal for at least 1 year.

Melanoma Patients

7. The patient has a diagnosis of primary melanoma. Breast Cancer Patients

8. The patient has a diagnosis of primary breast cancer.

9. Patients with pure ductal carcinoma in situ (DCIS) or non-invasive carcinoma if lymph
node biopsy is part of the surgical plan.

Exclusion Criteria:

1. The patient is pregnant or lactating.

2. The patient has clinical or radiological evidence of metastatic cancer including
palpably abnormal or enlarged lymph nodes (i.e., all patients should be any T,N0,M0,
see Appendix D and E).

3. The patient has a known hypersensitivity to Lymphazurin.

4. The patient has participated in another investigational drug study within 30 days of
scheduled surgery.

Melanoma Patients

5. The patient has a tumor with a Breslow depth less than 0.75mm.

6. Patient has had preoperative chemotherapy, immunotherapy, or radiation therapy.

7. Patient has been diagnosed with a prior invasive melanoma that would occur on the
same body region or potentially draining to the same nodal basin or patients with
truncal or extremity primary melanoma who has had a prior breast cancer potentially
draining to the same axillary nodal basin.

8. Patient has undergone node basin surgery of any type or radiation to the nodal
basin(s) potentially draining the primary melanoma.

9. Patient has undergone a wide excision for their primary melanoma (>1 cm in dimension)
or complex reconstruction (rotation, free flap, or skin graft of any type).

Breast Cancer Patients

10. The patient has bilateral primary breast cancers or multiple tumors within their

11. Patient has had prior surgical procedures such as breast implants, reduction
mammoplasty, or axillary surgery.

12. Patient is scheduled for bilateral mastectomy unless for cosmetic reasons and the
contraindicated breast will not undergo lymph node mapping.

13. Patient has had preoperative radiation therapy to the affected breast or axilla.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Outcome Measure:

Concordance of Blue Dye and Lymphoseek

Outcome Description:

The proportion of lymph nodes detected intraoperatively by blue dye that were also detected by Lymphoseek.

Outcome Time Frame:

Surgery after injections of Lymphoseek and blue dye

Safety Issue:


Principal Investigator

Simon A Blackburn

Investigator Role:

Study Director

Investigator Affiliation:

Navidea Biopharmaceuticals


United States: Food and Drug Administration

Study ID:




Start Date:

June 2010

Completion Date:

April 2011

Related Keywords:

  • Breast Cancer
  • Melanoma
  • Lymphoseek
  • Breast Cancer
  • Melanoma
  • Experimental
  • Breast Neoplasms
  • Melanoma



John Wayne Cancer Institute Santa Monica, California  90404
The Ohio State University Columbus, Ohio  43210
H. Lee Moffitt Cancer Center Tampa, Florida  33612
UCSD Moores Cancer Center La Jolla, California  93093
University of Alabama, Birmingham Birmingham, Alabama  35233
University Hospitals Cleveland Cleveland, Ohio  44106
Califonia Pacific Medical Center San Francisco, California  94115
Breast Care Specialists Columbus, Ohio  43081