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

Primary Purpose

Head and Neck Squamous Cell Carcinoma (HNSCC)

Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Lymphoseek
Sponsored by
Navidea Biopharmaceuticals
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Head and Neck Squamous Cell Carcinoma (HNSCC) focused on measuring HNSCC

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 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.

Sites / Locations

  • University of Alabama, Birmingham
  • Moores UCSD Cancer Center
  • San Diego VA Hospital
  • University of Miami, Sylvester Comprehensive Cancer Center
  • University of Kansas Medical Center
  • University of Michigan Medical Center
  • University of Mississippi
  • University of Missouri-Ellis Fischel Cancer Center
  • University of Nebraska
  • Duke University Medical Center
  • The Ohio State University Comprehensive Cancer Center
  • Thomas Jefferson University
  • MD Anderson

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
May 28, 2009
Last Updated
August 6, 2014
Sponsor
Navidea Biopharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00911326
Brief Title
Evaluation of Sentinel Lymph Nodes in Head and Neck Squamous Cell Carcinoma
Official Title
A Ph 3, Prospective, Open-Label, Multicenter Study of Lymphoseek®-Identified Sentinel Lymph Nodes (SLNs) Relative to the Path Status of Non SLN in an Elective Neck Dissection in Cutaneous Head and Neck and Intraoral Squamous Cell Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
August 2014
Overall Recruitment Status
Terminated
Why Stopped
The trial was terminated early based on an interim review by the Data and Safety Monitoring Committee for positive efficacy outcome and no safety concerns.
Study Start Date
May 2009 (undefined)
Primary Completion Date
August 2013 (Actual)
Study Completion Date
August 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Navidea Biopharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Squamous Cell Carcinoma (HNSCC)
Keywords
HNSCC

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
101 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Lymphoseek
Other Intervention Name(s)
Tc-99m Tilmanocept (Lymphoseek)
Intervention Description
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
Primary Outcome Measure Information:
Title
False Negative Rate (FNR)
Description
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
Secondary Outcome Measure Information:
Title
Negative Predictive Value (NPV)
Description
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
Title
Overall Accuracy
Description
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
Title
Lymph Node Detection Rate
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: The patient has provided written informed consent with Health Insurance Portability and Accountability Act (HIPAA) authorization before participating in the study. 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. 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. Imaging of the regional nodal basin has been performed within 30 days of the planned lymphadenectomy. The patient is a candidate for surgical intervention, with intraoperative lymphatic mapping and END included in the surgical plan. 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. The patient is at least 18 years of age at the time of consent. The patient has an Eastern Cooperative Oncology Group (ECOG) status of Grade 0 - 2. 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: 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. The patient is pregnant or lactating. The patient has clinical or radiological evidence of metastatic cancer to the regional lymph nodes. 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. Patients who have had other nuclear imaging studies conducted within 15 days or consenting. The patient is actively receiving systemic cytotoxic chemotherapy. Patient is currently participating in another investigational drug study or participated within 30 days prior to consenting. Patient is on immunosuppressive or anti-monocyte or immunomodulatory therapy.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bonnie C Abbruzzese, MS RD
Organizational Affiliation
Navidea Biopharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama, Birmingham
City
Birminham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Moores UCSD Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
San Diego VA Hospital
City
San Diego
State/Province
California
ZIP/Postal Code
92161
Country
United States
Facility Name
University of Miami, Sylvester Comprehensive Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
University of Michigan Medical Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
University of Mississippi
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Facility Name
University of Missouri-Ellis Fischel Cancer Center
City
Columbia
State/Province
Missouri
ZIP/Postal Code
65203
Country
United States
Facility Name
University of Nebraska
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
The Ohio State University Comprehensive Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
MD Anderson
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
25670018
Citation
Agrawal A, Civantos FJ, Brumund KT, Chepeha DB, Hall NC, Carroll WR, Smith RB, Zitsch RP, Lee WT, Shnayder Y, Cognetti DM, Pitman KT, King DW, Christman LA, Lai SY. [(99m)Tc]Tilmanocept Accurately Detects Sentinel Lymph Nodes and Predicts Node Pathology Status in Patients with Oral Squamous Cell Carcinoma of the Head and Neck: Results of a Phase III Multi-institutional Trial. Ann Surg Oncol. 2015 Oct;22(11):3708-15. doi: 10.1245/s10434-015-4382-x. Epub 2015 Feb 11.
Results Reference
derived
PubMed Identifier
24051744
Citation
Marcinow AM, Hall N, Byrum E, Teknos TN, Old MO, Agrawal A. Use of a novel receptor-targeted (CD206) radiotracer, 99mTc-tilmanocept, and SPECT/CT for sentinel lymph node detection in oral cavity squamous cell carcinoma: initial institutional report in an ongoing phase 3 study. JAMA Otolaryngol Head Neck Surg. 2013 Sep;139(9):895-902. doi: 10.1001/jamaoto.2013.4239.
Results Reference
derived

Learn more about this trial

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

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