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

NCT00911326 | Terminated Phase 3 Results DMC

• 1 other identifier: NEO3-06
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 13

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.

Conditions

Head and Neck Squamous Cell Carcinoma (HNSCC)

Keywords

HNSCC

Outcome Measures

Primary Outcomes (1)

• 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.

  Surgery after injection of Lymphoseek

Secondary Outcomes (3)

• Negative Predictive Value (NPV)

  Surgery after injection of Lymphoseek

• Overall Accuracy

  Surgery after injection of Lymphoseek

• Lymph Node Detection Rate

  Surgery after injection of Lymphoseek

Interventions

Lymphoseek DRUG

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

Also known as: Tc-99m Tilmanocept (Lymphoseek)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Navidea Biopharmaceuticals: lead

Study Sites (13)

University of Alabama, Birmingham

Birminham, Alabama, 35294, United States

Location

Moores UCSD Cancer Center

La Jolla, California, 92093, United States

Location

San Diego VA Hospital

San Diego, California, 92161, United States

Location

University of Miami, Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Michigan Medical Center

Ann Arbor, Michigan, 48109, United States

Location

University of Mississippi

Jackson, Mississippi, 39216, United States

Location

University of Missouri-Ellis Fischel Cancer Center

Columbia, Missouri, 65203, United States

Location

University of Nebraska

Omaha, Nebraska, 68198, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

Related Publications (2)

• 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.

  PMID: 25670018 DERIVED

• 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.

  PMID: 24051744 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

technetium-diethylenetriaminepentaacetic acid-mannosyl-dextran

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Limitations and Caveats

The study was prospectively structured to include an interim analysis at 33.3% enrollment. The trial was terminated early based on an interim review by the Data and Safety Monitoring Committee for positive efficacy outcome and lack of safety concern.

Results Point of Contact

• Title: Dr. Frederick O. Cope, Chief Scientific Officer
• Organization: Navidea Biopharmaceuticals

fcope@navidea.com

614-793-7500

Study Officials

• Bonnie C Abbruzzese, MS RD

  Navidea Biopharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2009
• First Posted: June 1, 2009
• Study Start: May 1, 2009
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: August 8, 2014
• Results First Posted: August 8, 2014

Record last verified: 2014-08

Locations

US (13)