Trial of Lymphoseek in Intraoperative Localization of Lymph Nodes in Breast Cancer and Melanoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Navidea Biopharmaceuticals
ClinicalTrials.gov Identifier:
NCT00671918
First received: April 30, 2008
Last updated: June 6, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Melanoma
Drug: Lymphoseek
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Navidea Biopharmaceuticals:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 186
Study Start Date: April 2008
Study Completion Date: July 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lymphoseek, Lymphatic mapping, Injection Drug: Lymphoseek
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The patient has provided written informed consent with HIPAA authorization before participating in the study, as has his/her responsible caregiver, if applicable.
  • The patient is a candidate for surgical intervention, with lymph node mapping being a part of the surgical plan.
  • The patient is at least 18 years of age at the time of consent.
  • The patient has an ECOG performance status of Grade 0 - 2 [8].
  • The patient has a clinical negative node status at the time of study entry.
  • If of child bearing 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.
  • The patient is currently not participating in another investigational drug study.

Melanoma Patients

  • The patient has a diagnosis of primary melanoma.

Breast Cancer Patients

  • The patient has a diagnosis of primary breast cancer.
  • Patients with pure ductal carcinoma in situ (DCIS) or non-invasive carcinoma if lymph node biopsy is part of the surgical plan.

Exclusion Criteria:

  • The patient is pregnant or lactating;
  • 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);
  • The patient has a known hypersensitivity to Lymphazurin or Patent Bleu V.

Melanoma Patients

  • The patient has a tumor with a Breslow depth less than 0.75mm.;
  • Patients that have had preoperative chemotherapy, immunotherapy or radiation therapy;
  • Patients 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;
  • Patients who have undergone node basin surgery of any type or radiation to the nodal basin(s) potentially draining the primary melanoma;
  • Patients who have 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

  • The patient has bilateral primary breast cancers or multiple tumors within their breast;
  • Patients that have had prior surgical procedures such as breast implants, reduction mammoplasty or axillary surgery;
  • Patients scheduled for bilateral mastectomy for any reason;
  • Patients that have had preoperative radiation therapy to the affected breast or axilla
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00671918

Locations
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
Israel
Schlomo Schneebaum, M.D.
Tel Aviv, Israel, 64239
Sponsors and Collaborators
Navidea Biopharmaceuticals
Investigators
Study Director: Richard Orahood, M.D. Navidea Biopharmaceuticals
  More Information

Publications:
Krag DN. Gamma-probe-guided resection of axillary sentinel nodes. Presented at the 48th annual symposium of the Society of Surgical Oncology, March 23-25, 1995, Boston MA.
Guiliano AE. Axillary node mapping for breast cancer. Presented at the 48th annual symposium of the Society of Surgical Oncology, March 23-25, 1995, Boston MA.

Responsible Party: Navidea Biopharmaceuticals
ClinicalTrials.gov Identifier: NCT00671918     History of Changes
Other Study ID Numbers: NEO3-05
Study First Received: April 30, 2008
Results First Received: April 13, 2013
Last Updated: June 6, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Navidea Biopharmaceuticals:
breast cancer
lymph nodes
melanoma
surgery

Additional relevant MeSH terms:
Breast Neoplasms
Melanoma
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Dextrans
Technetium Tc 99m Pentetate
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Plasma Substitutes
Blood Substitutes
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Radiopharmaceuticals
Diagnostic Uses of Chemicals

ClinicalTrials.gov processed this record on August 28, 2014