Lymphoseek® as Lymphoid Tissue Targeting Agents in Colon Cancer(CNC)
Lymphoseek® as Lymphoid Tissue Targeting Agents in Colon Cancer(CNC)
45 patients undergoing a colon (large bowel/intestine)removal operation for the diagnosis of
 colon cancer will be included in this study. During colon operation the affected portion of
 the colon is removed. In addition, lymph nodes are included in the specimen and evaluated by
 a pathologist. Analysis of the lymph nodes in the specimen are important because this is an
 important aspect of determining the stage of the cancer.

 Once the standard technique is used for the colon removal operation and the specimen is
 removed it will be injected with two drugs to help identify the lymph nodes. One is a blue
 dye and the other a radiotracer. The colon and ALL of the lymph nodes will then be sent for
 the standard pathologic evaluation. The patient themselves will never be injected with these
 drugs being used for research.

 Following the standard lymph node evaluation, an additional pathologist at an outside
 research facility will further examine the lymph nodes in the specimen using more in depth
 techniques which are above and beyond the standard of care.

 The results of all the pathologic tests will be conveyed to the surgeon of record to help in
 their decision making regarding further treatment.

 The study hypothesis is that radiotracer will be at least as effective as blue dye in
 identifying the lymph nodes most likely to harbor cancer cells (sentinel nodes). Once
 identified, these sentinel nodes can then undergo a more in depth review leading to improved
 staging of colorectal cancer and more accurate treatment.
This study is a single center, open-label, within patient's tissue ex vivo comparative study
 of Lymphoseek (Lymphoseek (Technetium Tc 99m Tilmanocept) is a radiotracer that accumulates
 in lymphatic tissue by binding to a mannose binding receptor that resides on the surface of
 dendritic cells and macrophages. Lymphoseek has a diameter of about 5 nm, which is
 substantially smaller than current radiolabeled 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
 bladder.)and vital blue dye (Patent Bleu V) in the detection of excised lymph nodes in
 patients with known cancer of the colon.

 The colon segment with tumor and the anticipated involved nodal bed will be removed intact.
 After the surgical procedure is completed, the specimen is instantly taken to an extra table
 in the operating room. It is performed just after the specimen is taken out. The colonic
 specimen is incised longitudinally on the antimesenteric side.

 Lymphatic mapping is employed on the specimen by using first injection Lymphoseek (50 µg/2
 mCi) in 0.1-1.0 ml, followed in 15-30 min by 1 ml 1% blue dye, each injected subserosally and
 submucosally around the tumor (peritumoral sites employed) by using tuberculin syringe. After
 5-7 minutes of massage with little circulatory movements on the lesion, the marking agents
 are moved into the lymphatic paths to the sentinel lymph nodes(SLN)in the mesentery.

 By low level diathermy, sharp dissection of lymphatic path(s) to the SLN(s) may be existent.

 Blue nodes shall be removed first by visual inspection. This inspection and dissection shall
 last not longer than 20 minutes. Each blue node will then be assessed for counts as well as
 color and the "hot" rule (3σ) applied as described below.

 Following blue node removal, each sentinel lymph node can be removed from the basin and
 marked before the specimen is submitted for pathologic appraisal.

 The Lymphoseek-designated (localized) lymph nodes are defined as lymph nodes that have a
 gamma detector count greater than the sum of 3 square roots of the mean background count
 (i.e., standard deviation) added to the mean background count. This is referred to hereafter
 as the "3σ rule" and as the "threshold criteria". If the gamma detector used cannot obtain
 gamma counts in three 2-second intervals, then one 10-second count may be used to detect
 gamma counts. Any lymph node count not meeting this threshold criterion will be considered a
 negative (non-localized) finding. The background count may be obtained by taking the 2-second
 counts or the 10 second counts with the handheld gamma probe extended at least 100 cm away
 from the injection site and the probe pointed away from anyLymphoseek source (syringes,
 injection site, isotope-contaminated materials).

 Probing of the area will be complete when all selected node counts are negative by use of the
 threshold criteria. The surgeon will continue with visualization and palpation according to
 local practice to ensure that no grossly positive lymph nodes remain at the site of
 resection. To confirm the in vivo procedure, assessment of presence of a blue hue and a set
 of three 2-second counts or one 10-second count will be recorded for the excised lymph nodes.
 The mean count of the ex vivo lymph nodes will be compared to the mean of room background
 counts, and the same threshold criteria used to determine a positive finding for the in vivo
 nodes will be applied to the ex vivo specimens.

 All removed lymph nodes will be sent to pathology for further evaluation. All lymph nodes
 will undergo enhanced pathological evaluation including serial sectioning with H&E staining
 as well as immunohistochemical (IHC) markers A- The primary objective of efficacy is the
 concordance of in vivo detection rates of Lymphoseek and VBD in excised lymph nodes as tissue
 phenotype is confirmed by histology.

 B- The primary objective is the assessment of the excised lymph node(s) to confirm the
 presence/absence of tumor metastases in all nodes and a contrast of pathology findings in per
 agent-found nodes versus all non-agent-based removed nodes.

 Secondary evaluations will include localization rates (identification of any hot and/or blue
 node), degree of localization (node number/patient's ex vivo total tissue), counts localized
 per node, and time to localization and stabilization.
Inclusion Criteria:

 -  The patient has provided written informed consent with Health Insurance Portability
 and Accountability Act (HIPAA) authorization.

 -  The patient has a diagnosis of colon cancer and is a candidate for surgical
 intervention, with ex vivo 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 Eastern Cooperative Oncology Group (ECOG) performance status of
 Grade 0 - 2.

 -  The patient has a clinical negative node status at the time of study entry (i.e.,
 Tis-4, N0, M0).

 Exclusion Criteria:

 -  The patient has clinical or radiological evidence of metastatic cancer including
 palpably abnormal or enlarged lymph nodes.

 -  The patient has undergone node basin surgery of any type or radiation to the nodal
 basin(s).

 -  The patient has undergone radiation therapy or chemotherapy treatment within the
 previous 45 days.