Evaluation of Sentinel Lymph Nodes in Head and Neck Squamous Cell Carcinoma

• The secondary study objective is to determine the sensitivity, negative predictive value and overall accuracy of Lymphoseek detected SLNs relative to the pathological status of lymph nodes in the END. [ Time Frame: 30 days ] [ Designated as safety issue: No ]
• Additional secondary endpoints include the detection rate of SLNs by Lymphoseek and the rate of tumor detection in nodes sampled in the END. [ Time Frame: 30 days ] [ Designated as safety issue: No ]

The purpose of this study is to determine the false negative rate (FNR) associated with Lymphoseek-identified sentinel lymph nodes (SLNs) relative to the pathological status of non-sentinel lymph nodes in elective neck dissection (END) in head & neck SCC. NEO3-06 (this study) is a Phase 3 clinical trial designed to supplement NEO3-05, a Phase 3 clinical trial conducted in patients with breast cancer or melanoma. NEO3-05 is designed to establish Lymphoseek as an effective radio-diagnostic agent to be used in the intraoperative localization of lymph tissue (nodes) in the lymphatic pathway draining the primary site of a tumor.

Inclusion Criteria:

Subjects meeting all of the following inclusion criteria by the end of the screening phase should be considered for admission to the study:

1. The patient has provided written informed consent with HIPAA authorization before participating in the study.
2. The patient has a diagnosis of primary squamous cell carcinoma of the head and neck either cutaneous or intra-oral that is anatomically located in: mucosal lip, buccal mucosa, lower alveolar ridge, upper alveolar ridge, retromolar gingiva (retromolar trigone), floor of the mouth, hard palette or oral (mobile) tongue, stage T1-T4a, N0, M0. (See Appendix A: TNM Staging AND Inclusion tracking Figure 1, above)
3. Clinical nodal staging (N0) has been confirmed by negative results from contrast CT scan or gadolinium-enhanced MRI or lateral and central neck ultrasound. PET scan cannot be used for this evaluation.
4. Imaging of the regional nodal basin has been performed within 30 days of the planned lymphadenectomy.
5. The patient is a candidate for surgical intervention, with ILM and END included in the surgical plan.

6. Patients with prior malignancy are allowed provided the patient meets the following criteria:

   Underwent potentially curative therapy for all prior malignancies and is deemed low risk for recurrence; AND No malignancy for the past 5 years (except effectively treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix effectively treated with surgery alone, lobular carcinoma in situ of the ipsilateral or contralateral breast treated with surgery alone, or carcinoma of the mouth that is in situ or minimally invasive) and no evidence of recurrence.

7. The patient is at least 18 years of age at the time of consent.
8. The patient has an ECOG status of Grade 0 - 2 (Appendix B).
9. If the patient is a female, the patient has a confirmed negative pregnancy test within 72 hours priors to administration of Lymphoseek, OR has documentation of surgical sterilization, OR has documented evidence of postmenopausal status for at least 1 year.

Exclusion Criteria:

Patients meeting any of the following exclusion criteria at the end of the screening phase will not be enrolled in the study:

1. The patient has a diagnosis of squamous cell carcinoma of the head and neck in the following anatomical areas: non-mobile base of the tongue, oral pharynx, nasal pharynx, hypo-pharynx and larynx.
2. The patient is pregnant or lactating.
3. The patient has clinical or radiological evidence of metastatic cancer to the regional lymph nodes.
4. Patients with a history of neck dissection, or gross injury to the neck that would preclude reasonable surgical dissection for this study, or radiotherapy to the neck.
5. Patients who have had other nuclear imaging studies conducted within 15 days or consenting.
6. The patient is actively receiving systemic cytotoxic chemotherapy.
7. Patient is currently participating in another investigational drug study or participated within 30 days prior to consenting.
8. Patient is on immunosuppressive or anti-monocyte or immunomodulatory therapy.