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Breast CancerPhase 3NCT00671918

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

A Phase 3 study testing Lymphoseek in people with Breast Cancer and Melanoma, run by Navidea Biopharmaceuticals at 15 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer, Melanoma
What is being tested?
Lymphoseek
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
186 participants
Where
15 sitesin 2 countries
Study dates
Apr 2008to Jul 2009
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 12Show fewer
  • 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.

Who cannot join

  • 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;
Show all 14Show fewer
  • 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

Trial locations and contacts

15 sites in 2 countries.

15 sites in 2 countries

United States14 sites
  • Barbara Michna, M.D

    Alexander City, Alabama, 35010

  • Helen Krontiras, M.D.

    Birmingham, Alabama, 35294

  • Thomas Frazier, M.D.

    Bryn Mawr, Pennsylvania, 19010

  • Julian Kim, M.D.

    Cleveland, Ohio, 44106

  • Bruce Averbook, M.D

    Cleveland, Ohio, 44109

  • Stephen Povoski, M.D.

    Columbus, Ohio, 43210

  • Anne Wallace, M.D.

    La Jolla, California, 92093

  • Ken Deck, M.D.

    Laguna Hills, California, 92653

  • Eli Avisar, M.D.

    Miami, Florida, 33101

  • Ned Carp, M.D.

    Philadelphia, Pennsylvania, 19096

  • Steve Martinez, M.D.

    Sacramento, California, 95817

  • Mark Faries, M.D.

    Santa Monica, California, 90404

  • Charles Cox, M.D.

    Tampa, Florida, 33612

  • Vernon Sondak, M.D.

    Tampa, Florida, 33612

Other trials in United States

Israel1 site
  • Schlomo Schneebaum, M.D.

    Tel Aviv, 64239

Other trials in Israel

About this study

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

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.

Read the 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.

Being tested
Lymphoseek
Keywords
breast cancer, lymph nodes, melanoma, surgery
Medical subject headings
Breast Neoplasms, Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LymphoseekDrug

    Also called technetium Tc 99m tilmanocept

    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.

Study groups in NCT00671918
Study groupRoleWhat they receive
Lymphoseek, Lymphatic mapping, InjectionExperimentalNot described
Receives: Drug: Lymphoseek

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Concordance of Blue Dye and Lymphoseek

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

    Measured: Surgery after injections of Lymphoseek and blue dye

Secondary outcomes (1)
  1. Reverse Concordance of Blue Dye and Lymphoseek

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

    Measured: Surgery after injections of Lymphoseek and blue dye

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 May 2008 (estimated)
  2. Study startApr 2008
  3. Primary completionJun 2009
  4. Study completionJul 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
186 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00671918
Sponsor's protocol ID
NEO3-05
Status last verified
Jun 2013
First submitted
30 Apr 2008
Last updated
17 Jun 2013
Data monitoring committee
No

Publications

  • Morton DL, Thompson JF, Cochran AJ, Mozzillo N, Elashoff R, Essner R, Nieweg OE, Roses DF, Hoekstra HJ, Karakousis CP, Reintgen DS, Coventry BJ, Glass EC, Wang HJ; MSLT Group. Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med. 2006 Sep 28;355(13):1307-17. doi: 10.1056/NEJMoa060992.

    PubMed 17005948
  • Giuliano AE, Kirgan DM, Guenther JM, Morton DL. Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg. 1994 Sep;220(3):391-8; discussion 398-401. doi: 10.1097/00000658-199409000-00015.

    PubMed 8092905
  • Morton DL, Cochran AJ, Thompson JF, Elashoff R, Essner R, Glass EC, Mozzillo N, Nieweg OE, Roses DF, Hoekstra HJ, Karakousis CP, Reintgen DS, Coventry BJ, Wang HJ; Multicenter Selective Lymphadenectomy Trial Group. Sentinel node biopsy for early-stage melanoma: accuracy and morbidity in MSLT-I, an international multicenter trial. Ann Surg. 2005 Sep;242(3):302-11; discussion 311-3. doi: 10.1097/01.sla.0000181092.50141.fa.

    PubMed 16135917
  • Rossi CR, De Salvo GL, Trifiro G, Mocellin S, Landi G, Macripo G, Carcoforo P, Ricotti G, Giudice G, Picciotto F, Donner D, Di Filippo F, Montesco MC, Casara D, Schiavon M, Foletto M, Baldini F, Testori A. The impact of lymphoscintigraphy technique on the outcome of sentinel node biopsy in 1,313 patients with cutaneous melanoma: an Italian Multicentric Study (SOLISM-IMI). J Nucl Med. 2006 Feb;47(2):234-41.

    PubMed 16455628
  • Albertini JJ, Lyman GH, Cox C, Yeatman T, Balducci L, Ku N, Shivers S, Berman C, Wells K, Rapaport D, Shons A, Horton J, Greenberg H, Nicosia S, Clark R, Cantor A, Reintgen DS. Lymphatic mapping and sentinel node biopsy in the patient with breast cancer. JAMA. 1996 Dec 11;276(22):1818-22.

    PubMed 8946902
  • Veronesi U, Paganelli G, Galimberti V, Viale G, Zurrida S, Bedoni M, Costa A, de Cicco C, Geraghty JG, Luini A, Sacchini V, Veronesi P. Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes. Lancet. 1997 Jun 28;349(9069):1864-7. doi: 10.1016/S0140-6736(97)01004-0.

    PubMed 9217757
  • Giuliano AE, Jones RC, Brennan M, Statman R. Sentinel lymphadenectomy in breast cancer. J Clin Oncol. 1997 Jun;15(6):2345-50. doi: 10.1200/JCO.1997.15.6.2345.

    PubMed 9196149
  • Krag D, Weaver D, Ashikaga T, Moffat F, Klimberg VS, Shriver C, Feldman S, Kusminsky R, Gadd M, Kuhn J, Harlow S, Beitsch P. The sentinel node in breast cancer--a multicenter validation study. N Engl J Med. 1998 Oct 1;339(14):941-6. doi: 10.1056/NEJM199810013391401.

    PubMed 9753708
  • Krag DN, Weaver DL, Alex JC, Fairbank JT. Surgical resection and radiolocalization of the sentinel lymph node in breast cancer using a gamma probe. Surg Oncol. 1993 Dec;2(6):335-9; discussion 340. doi: 10.1016/0960-7404(93)90064-6.

    PubMed 8130940
  • 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.

  • Wallace AM, Hoh CK, Vera DR, Darrah DD, Schulteis G. Lymphoseek: a molecular radiopharmaceutical for sentinel node detection. Ann Surg Oncol. 2003 Jun;10(5):531-8. doi: 10.1245/aso.2003.07.012.

    PubMed 12794019
  • Ellner SJ, Hoh CK, Vera DR, Darrah DD, Schulteis G, Wallace AM. Dose-dependent biodistribution of [(99m)Tc]DTPA-mannosyl-dextran for breast cancer sentinel lymph node mapping. Nucl Med Biol. 2003 Nov;30(8):805-10. doi: 10.1016/j.nucmedbio.2003.10.001.

    PubMed 14698783
  • Posther KE, McCall LM, Blumencranz PW, Burak WE Jr, Beitsch PD, Hansen NM, Morrow M, Wilke LG, Herndon JE 2nd, Hunt KK, Giuliano AE. Sentinel node skills verification and surgeon performance: data from a multicenter clinical trial for early-stage breast cancer. Ann Surg. 2005 Oct;242(4):593-9; discussion 599-602. doi: 10.1097/01.sla.0000184210.68646.77.

    PubMed 16192820
  • Barnwell JM, Arredondo MA, Kollmorgen D, Gibbs JF, Lamonica D, Carson W, Zhang P, Winston J, Edge SB. Sentinel node biopsy in breast cancer. Ann Surg Oncol. 1998 Mar;5(2):126-30. doi: 10.1007/BF02303845.

    PubMed 9527265

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Lymphoseek in people with Breast Cancer and Melanoma, run by Navidea Biopharmaceuticals at 15 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States, Israel. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Jun 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Concordance of Blue Dye and Lymphoseek (time frame: Surgery after injections of Lymphoseek and blue dye). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00671918, which also lists 50 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2013.

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