Breast CancerPhase 3NCT01106040
Breast and Melanoma Trial With Lymphoseek to Identify Lymph Nodes
A Phase 3 study testing Lymphoseek in people with Breast Cancer and Melanoma, run by Navidea Biopharmaceuticals at 8 sites in United States.
Trial summary
Data from this pivotal clinical trial will be used to support a marketing application (i.e., NDA) of Navidea's Lymphoseek for use in anatomical delineation of lymphoid 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
- 163 participants
- Where
- 8 sitesUnited States
- Study dates
- Jun 2010to Apr 2011
- 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.
- 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 (see Appendix A).
- 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).
- 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.
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- 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, see Appendix D and E).
- The patient has a known hypersensitivity to Lymphazurin.
- The patient has participated in another investigational drug study within 30 days of scheduled surgery.
- Melanoma Patients
- The patient has a tumor with a Breslow depth less than 0.75mm.
Show all 15Show fewer
- Patient has had preoperative chemotherapy, immunotherapy, or radiation therapy.
- 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.
- Patient has undergone node basin surgery of any type or radiation to the nodal basin(s) potentially draining the primary melanoma.
- 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
- The patient has bilateral primary breast cancers or multiple tumors within their breast.
- Patient has had prior surgical procedures such as breast implants, reduction mammoplasty, or axillary surgery.
- Patient is scheduled for bilateral mastectomy unless for cosmetic reasons and the contraindicated breast will not undergo lymph node mapping.
- Patient has had preoperative radiation therapy to the affected breast or axilla.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
University of Alabama, Birmingham
Birmingham, Alabama, 35294
University Hospitals Cleveland
Cleveland, Ohio, 44106
Breast Care Specialists
Columbus, Ohio, 43081
The Ohio State University
Columbus, Ohio, 43210
UCSD Moores Cancer Center
La Jolla, California, 92093
Califonia Pacific Medical Center
San Francisco, California, 94115
John Wayne Cancer Institute
Santa Monica, California, 90404
H. Lee Moffitt Cancer Center
Tampa, Florida, 33612
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) of Navidea's Lymphoseek for use in anatomical delineation of lymphoid tissue (nodes) in the lymphatic pathway draining the primary site of a tumor.
Multicenter, open-label, within-patient comparative study of Lymphoseek and vital blue dye in the detection of excised lymph nodes in patients with known melanoma and breast cancer. All patients will receive a single dose of 50 µg Lymphoseek radiolabeled with 0.5 or 2.0 mCi Tc 99m and vital blue dye.
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 (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 purity.
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.
- Conditions
- Breast Cancer, Melanoma
- Being tested
- Lymphoseek
- Keywords
- Lymphoseek, Breast Cancer, Melanoma, Experimental
- 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
The total volume of Lymphoseek injection will be between 0.1 - 1.0 mL.
| Study group | Role | What they receive |
|---|---|---|
| Lymphoseek, Lymphatic mapping, Injection | Experimental | Not described Receives: Drug: Lymphoseek |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
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.
- First posted19 Apr 2010 (estimated)
- Study startJun 2010
- Primary completionApr 2011
- Study completionApr 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 163 participants (actual)
Sponsor and investigators
- Lead sponsor
- Navidea Biopharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Simon A Blackburn, Study director, Navidea Biopharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01106040
- Sponsor's protocol ID
- NEO3-09
- Status last verified
- Jun 2013
- First submitted
- 14 Apr 2010
- Last updated
- 17 Jun 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Wallace AM, Han LK, Povoski SP, Deck K, Schneebaum S, Hall NC, Hoh CK, Limmer KK, Krontiras H, Frazier TG, Cox C, Avisar E, Faries M, King DW, Christman L, Vera DR. Comparative evaluation of [(99m)tc]tilmanocept for sentinel lymph node mapping in breast cancer patients: results of two phase 3 trials. Ann Surg Oncol. 2013 Aug;20(8):2590-9. doi: 10.1245/s10434-013-2887-8. Epub 2013 Mar 17.
PubMed 23504141Sondak VK, King DW, Zager JS, Schneebaum S, Kim J, Leong SP, Faries MB, Averbook BJ, Martinez SR, Puleo CA, Messina JL, Christman L, Wallace AM. Combined analysis of phase III trials evaluating [(9)(9)mTc]tilmanocept and vital blue dye for identification of sentinel lymph nodes in clinically node-negative cutaneous melanoma. Ann Surg Oncol. 2013 Feb;20(2):680-8. doi: 10.1245/s10434-012-2612-z. Epub 2012 Oct 3.
PubMed 23054107
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01106040
- Acronym / sponsor ID
- NEO3-09
- Conditions
- Breast Cancer, Melanoma
- Keywords
- Lymphoseek, Breast Cancer, Melanoma, Experimental
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 163 participants (actual)
- Lead sponsor
- Navidea BiopharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jun 2010
- Primary completion
- Apr 2011 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 19 Apr 2010 (estimated)
- Results
- Posted 3 Jun 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Data from this pivotal clinical trial will be used to support a marketing application (i.e., NDA) of Navidea's Lymphoseek for use in anatomical delineation of lymphoid tissue (nodes) in the lymphatic pathway draining the primary site of a tumor.
Multicenter, open-label, within-patient comparative study of Lymphoseek and vital blue dye in the detection of excised lymph nodes in patients with known melanoma and breast cancer. All patients will receive a single dose of 50 µg Lymphoseek radiolabeled with 0.5 or 2.0 mCi Tc 99m and vital blue dye.
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 (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 purity.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lymphoseek, Lymphatic mapping, Injection | Experimental | Drug: Lymphoseek |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- The patient has provided written informed consent with HIPAA authorization.
- 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 (see Appendix A).
- 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).
Key exclusion criteria (15 listed)
- 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, see Appendix D and E).
- The patient has a known hypersensitivity to Lymphazurin.
- The patient has participated in another investigational drug study within 30 days of scheduled surgery.
- Melanoma Patients
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LymphoseekAlso: technetium Tc 99m tilmanoceptThe total volume of Lymphoseek injection will be between 0.1 - 1.0 mL. | Drug | Lymphoseek, Lymphatic mapping, Injection |
Primary outcome
Concordance of Blue Dye and Lymphoseek
Time frame: Surgery after injections of Lymphoseek and blue dye
The proportion of lymph nodes detected intraoperatively by blue dye that were also detected by Lymphoseek.
1 secondary outcome
Reverse Concordance of Blue Dye and Lymphoseek
Time frame: Surgery after injections of Lymphoseek and blue dye
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23504141Wallace AM, Han LK, Povoski SP, Deck K, Schneebaum S, Hall NC, Hoh CK, Limmer KK, Krontiras H, Frazier TG, Cox C, Avisar E, Faries M, King DW, Christman L, Vera DR. Comparative evaluation of [(99m)tc]tilmanocept for sentinel lymph node mapping in breast cancer patients: results of two phase 3 trials. Ann Surg Oncol. 2013 Aug;20(8):2590-9. doi: 10.1245/s10434-013-2887-8. Epub 2013 Mar 17.
- Results publication: PubMed 23054107Sondak VK, King DW, Zager JS, Schneebaum S, Kim J, Leong SP, Faries MB, Averbook BJ, Martinez SR, Puleo CA, Messina JL, Christman L, Wallace AM. Combined analysis of phase III trials evaluating [(9)(9)mTc]tilmanocept and vital blue dye for identification of sentinel lymph nodes in clinically node-negative cutaneous melanoma. Ann Surg Oncol. 2013 Feb;20(2):680-8. doi: 10.1245/s10434-012-2612-z. Epub 2012 Oct 3.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Simon A Blackburn study director
Navidea Biopharmaceuticals
8 sites in 1 country: see every site and its status.
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 8 sites in United States.
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 10 inclusion and 15 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 8 sites in United States. 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 NCT01106040, which also lists 2 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.