Head and Neck Squamous Cell Carcinoma (HNSCC)
Conditions
Keywords
HNSCC
Brief summary
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 squamous cell carcinoma (HNSCC). NEO3-06 (this study) is a Phase 3 clinical trial designed to supplement NEO3-05, a completed Phase 3 clinical trial conducted in patients with breast cancer or melanoma. NEO3-05 was 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.
Interventions
DRUGLymphoseek
Single injection of 50 micrograms Lymphoseek radiolabeled with either 0.5 mCi (for same day surgery) or 2.0 mCi (for next day surgery) of Tc 99m
Sponsors
Navidea Biopharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 Health Insurance Portability and Accountability Act (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. 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 intraoperative lymphatic mapping 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 Eastern Cooperative Oncology Group (ECOG) status of Grade 0 - 2. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| False Negative Rate (FNR) | Surgery after injection of Lymphoseek | The FNR is calculated as a percentage from the ratio of false negatives to the sum of true positives plus false negatives. The FNR point estimate was the observed rate and was made on a per-patient basis relative to patients with pathology-positive nodes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Negative Predictive Value (NPV) | Surgery after injection of Lymphoseek | The NPV is calculated as a percentage from the ratio of true negatives to the sum of true negatives plus false negatives. The NPV point estimate was the observed rate and was made on a per-patient basis relative to patients predicted to be pathology-negative. |
| Overall Accuracy | Surgery after injection of Lymphoseek | The overall accuracy is calculated as a percentage from the ratio of (true positives + true negatives) / (true positives + false negatives + true negatives). The overall accuracy point estimate was the observed rate and was made on a per-patient basis relative to all patients in the intent-to-treat population. |
| Lymph Node Detection Rate | Surgery after injection of Lymphoseek | The rate of the subjects for whom Lymphoseek identified at least 1 sentinel lymph node. The detection rate point estimate was the observed rate and was made on a per-patient basis relative to all patients in the intent-to-treat population. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lymphoseek Enrolled patients who were administered any injection of Lymphoseek. | 85 |
| Total | 85 |
Baseline characteristics
| Characteristic | Lymphoseek |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 32 Participants |
| Age, Categorical Between 18 and 65 years | 53 Participants |
| Age, Continuous | 60.8 years STANDARD_DEVIATION 12.8 |
| Clinical tumor stage T1 | 26 participants |
| Clinical tumor stage T2 | 46 participants |
| Clinical tumor stage T3 | 7 participants |
| Clinical tumor stage T4 | 6 participants |
| Region of Enrollment United States | 85 participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 64 Participants |
| Tumor location Buccal mucosa | 8 participants |
| Tumor location Cutaneous | 6 participants |
| Tumor location Floor of the mouth | 20 participants |
| Tumor location Lower alveolar ridge | 3 participants |
| Tumor location Mucosal lip | 1 participants |
| Tumor location Oral tongue | 43 participants |
| Tumor location Retromolar gingiva | 4 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 85 |
| serious Total, serious adverse events | 11 / 85 |
Outcome results
Primary
False Negative Rate (FNR)
The FNR is calculated as a percentage from the ratio of false negatives to the sum of true positives plus false negatives. The FNR point estimate was the observed rate and was made on a per-patient basis relative to patients with pathology-positive nodes.
Time frame: Surgery after injection of Lymphoseek
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intent-to-treat (ITT) | False Negative Rate (FNR) | 2.56 % of pathology-positive participants |
Secondary
Lymph Node Detection Rate
The rate of the subjects for whom Lymphoseek identified at least 1 sentinel lymph node. The detection rate point estimate was the observed rate and was made on a per-patient basis relative to all patients in the intent-to-treat population.
Time frame: Surgery after injection of Lymphoseek
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intent-to-treat (ITT) | Lymph Node Detection Rate | 97.6 percentage of participants |
Secondary
Negative Predictive Value (NPV)
The NPV is calculated as a percentage from the ratio of true negatives to the sum of true negatives plus false negatives. The NPV point estimate was the observed rate and was made on a per-patient basis relative to patients predicted to be pathology-negative.
Time frame: Surgery after injection of Lymphoseek
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intent-to-treat (ITT) | Negative Predictive Value (NPV) | 97.8 % of participants predicted negative |
Secondary
Overall Accuracy
The overall accuracy is calculated as a percentage from the ratio of (true positives + true negatives) / (true positives + false negatives + true negatives). The overall accuracy point estimate was the observed rate and was made on a per-patient basis relative to all patients in the intent-to-treat population.
Time frame: Surgery after injection of Lymphoseek
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intent-to-treat (ITT) | Overall Accuracy | 98.8 percentage of participants |