Lymphoseek® as Lymphoid Tissue Targeting Agents in Colon Cancer(CNC)
Condition: Colon Cancer; Rectal Cancer
MeSH terms: Rectal Neoplasms; Colonic Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Lymphoseek and VBD Sln dissection
Intervention type(s): Drug
Intervention description(s): See detailed description of study design
Other intervention name(s): SLN dissection
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Sentinel lymph nodes; colon cancer; rectal cancer; immunohistochemistry