NCT04333537

Brief Summary

This phase II/III trial studies how well sentinel lymph node biopsy works and compares sentinel lymph node biopsy surgery to standard neck dissection as part of the treatment for early-stage oral cavity cancer. Sentinel lymph node biopsy surgery is a procedure that removes a smaller number of lymph nodes from your neck because it uses an imaging agent to see which lymph nodes are most likely to have cancer. Standard neck dissection, such as elective neck dissection, removes many of the lymph nodes in your neck. Using sentinel lymph node biopsy surgery may work better in treating patients with early-stage oral cavity cancer compared to standard elective neck dissection.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
686

participants targeted

Target at P75+ for phase_2

Timeline
61mo left

Started Sep 2020

Longer than P75 for phase_2

Geographic Reach
2 countries

106 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress53%
Sep 2020Apr 2031

First Submitted

Initial submission to the registry

March 26, 2020

Completed
8 days until next milestone

First Posted

Study publicly available on registry

April 3, 2020

Completed
6 months until next milestone

Study Start

First participant enrolled

September 23, 2020

Completed
10.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 27, 2031

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 27, 2031

Last Updated

May 4, 2026

Status Verified

April 1, 2026

Enrollment Period

10.6 years

First QC Date

March 26, 2020

Last Update Submit

April 28, 2026

Conditions

Outcome Measures

Primary Outcomes (3)

  • Patient-reported neck and shoulder function (Phase II/III)

    Will be evaluated and compared using the Neck Dissection Impairment Index (NDII), a 10-item tool between the two treatment arms. It is assumed that a 7.5-point between arm difference in the 6-month post-surgery NDII scores is clinically meaningful.

    Before surgery (Baseline), 3 weeks after surgery, 3, 6, 12 months after surgery

  • Patient reported quality of life (QOL) (Phase II)

    Will be measured using 3 questionnaires over 12-15 minutes.

    Before surgery (Baseline), 3 weeks after surgery, 3, 6, 12 months after surgery

  • Disease-free survival (DFS) (phase III)

    Measured using Cox proportional hazards model and the Kaplan-Meier method. Failure includes local/regional recurrence, distant metastasis, or death due to any cause.

    From randomization to local/regional recurrence, distant metastasis, or death due to any cause, whichever comes first, assessed up to 11 years

Secondary Outcomes (11)

  • Overall survival rate

    From randomization to death due to any cause, assessed up to 11 years

  • Loco-regional failure

    From the time of randomization to the date of failure, date of precluding event, or last known follow-up date, assessed up to 11 years

  • Distant metastasis

    From the time of randomization to the date of distant metastasis, date of precluding event, or last known follow-up date, assessed up to 11 years

  • Toxicity

    Time of primary endpoint analysis

  • Patient-reported shoulder-related QOL, function impairment and disability

    Baseline, 3 weeks, 3, 6, 12 months post-surgery

  • +6 more secondary outcomes

Other Outcomes (2)

  • Quality of life

    Baseline, 3 weeks, and 3, 6, 12 months post-surgery

  • DFS for low-risk patients

    From randomization to local/regional recurrence, distant metastasis, or death due to any cause, whichever comes first, assessed up to 11 years

Study Arms (2)

Group I (SLN biopsy)

EXPERIMENTAL

Patients receive an imaging agent via injection and undergo planar imaging and SPECT/CT over 1-2 hours. Patients then undergo SLN biopsy. Patients also undergo FDG PET/CT, CT, and/or chest x-ray at screening and during follow up.

Procedure: Chest RadiographyProcedure: Computed TomographyOther: Fludeoxyglucose F-18Drug: Imaging AgentProcedure: Planar ImagingProcedure: Positron Emission TomographyOther: Questionnaire AdministrationProcedure: Sentinel Lymph Node BiopsyProcedure: Single Photon Emission Computed Tomography

Group II (END)

ACTIVE COMPARATOR

Patients undergo standard END. Patients also undergo FDG PET/CT, CT, and/or chest x-ray at screening and during follow up.

Procedure: Chest RadiographyOther: Fludeoxyglucose F-18Procedure: Neck DissectionProcedure: Positron Emission TomographyOther: Questionnaire Administration

Interventions

Undergo chest x-ray

Also known as: Chest X-ray
Group I (SLN biopsy)Group II (END)

Undergo SPECT/CT scan and FDG PET/CT or CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography
Group I (SLN biopsy)

Undergo FDG PET/CT

Also known as: 18FDG, FDG, Fludeoxyglucose (18F), fludeoxyglucose F 18, Fludeoxyglucose F18, Fluorine-18 2-Fluoro-2-deoxy-D-Glucose, Fluorodeoxyglucose F18
Group I (SLN biopsy)Group II (END)

Receive imaging agent via injection

Also known as: Image Enhancement Agent
Group I (SLN biopsy)

Undergo standard elective neck dissection

Group II (END)

Undergo planar imaging

Group I (SLN biopsy)

Undergo FDG PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT
Group I (SLN biopsy)Group II (END)

Ancillary studies

Group I (SLN biopsy)Group II (END)

Undergo SLN biopsy

Also known as: Sentinel Node Biopsy, Sentinel node biopsy alone, SLNB, SNB
Group I (SLN biopsy)

Undergo SPECT/CT scan

Also known as: Medical Imaging, Single Photon Emission Computed Tomography, Single Photon Emission Tomography, Single-Photon Emission Computed, single-photon emission computed tomography, SPECT, SPECT imaging, SPECT SCAN, SPET, ST, tomography, emission computed, single photon, Tomography, Emission-Computed, Single-Photon
Group I (SLN biopsy)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Pathologically (histologically or cytologically) proven diagnosis of squamous cell carcinoma (SCC) of the oral cavity, including the oral (mobile) tongue, floor of mouth (FOM), mucosal lip, buccal mucosa, lower alveolar ridge, upper alveolar ridge, retromolar gingiva (retromolar trigone; RMT), or hard palate prior to registration
  • Appropriate stage for study entry (T1-2N0M0; American Joint Committee on Cancer \[AJCC\] 8th edition \[ed.\]) based on the following diagnostic workup:
  • History/physical examination within 42 days prior to registration
  • Imaging of head and neck within 42 days prior to registration
  • PET/CT scan or contrast neck CT scan, or gadolinium-enhanced neck magnetic resonance imaging (MRI) or lateral and central neck ultrasound; diagnostic quality CT is preferred and highly recommended as part of the PET/CT when possible
  • Imaging of chest within 42 days prior to registration
  • Chest x-ray, CT chest scan (with or without contrast), or PET/CT (with or without contrast)
  • Surgical assessment within 42 days prior to registration. Patient must be a candidate for surgical intervention with sentinel lymph node (SLN) biopsy and potential completion neck dissection (CND) or elective neck dissection (END)
  • Surgical resection of the primary tumor will occur through a transoral approach with anticipation of resection free margins
  • Age \>= 18
  • Zubrod performance status 0-2 within 42 days prior to registration
  • For women of child-bearing potential, negative serum or urine pregnancy test within 42 days prior to registration
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
  • Only patients who are able to read and understand English or French are eligible to participate as the mandatory patient reported NDII tool is only available in these languages
  • PRIOR TO STEP 2 RANDOMIZATION:
  • +4 more criteria

You may not qualify if:

  • Definitive clinical or radiologic evidence of regional (cervical) and/or distant metastatic disease
  • Prior non-head and neck invasive malignancy (except non-melanomatous skin cancer, including effectively treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or cervix) unless disease free for ≥ 2 years
  • Diagnosis of head and neck SCC in the oropharynx, nasopharynx, hypopharynx, and larynx
  • Unable or unwilling to complete NDII (baseline only)
  • Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for different cancer(s) is allowable
  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
  • Severe, active co-morbidity that would preclude an elective or completion neck dissection
  • Pregnancy and breast-feeding mothers
  • Incomplete resection of oral cavity lesion with a positive margin; however, an excisional biopsy is permitted
  • Prior surgery involving the lateral neck, including neck dissection or gross injury to the neck that would preclude surgical dissection for this trial. Prior thyroid and central neck surgery is permissible; biopsy is permitted. Note: Borderline suspicious nodes that are \>= 1 cm with radiographic finding suggestive of NOT malignant should be biopsied using ultrasound (U/S)-guided fine-needle aspiration (FNA) biopsy
  • Underlying or documented history of hematologic malignancy (e.g., chronic lymphocytic leukemia \[CLL\]) or other active disease capable of causing lymphadenopathy (e.g., sarcoidosis or untreated mycobacterial infection)
  • Actively receiving systemic cytotoxic chemotherapy, immunosuppressive, anti-monocyte or immunomodulatory therapy
  • Currently participating in another investigational therapeutic trial

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (106)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

ACTIVE NOT RECRUITING

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

RECRUITING

Mayo Clinic Hospital in Arizona

Phoenix, Arizona, 85054, United States

RECRUITING

Banner University Medical Center - Tucson

Tucson, Arizona, 85719, United States

SUSPENDED

University of Arizona Cancer Center-North Campus

Tucson, Arizona, 85719, United States

SUSPENDED

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

RECRUITING

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

ACTIVE NOT RECRUITING

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

RECRUITING

Stanford Cancer Institute Palo Alto

Palo Alto, California, 94304, United States

RECRUITING

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

ACTIVE NOT RECRUITING

UC San Diego Medical Center - Hillcrest

San Diego, California, 92103, United States

RECRUITING

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

RECRUITING

Stanford Cancer Center South Bay

San Jose, California, 95124, United States

RECRUITING

Yale University

New Haven, Connecticut, 06520, United States

RECRUITING

Smilow Cancer Hospital Care Center-Trumbull

Trumbull, Connecticut, 06611, United States

RECRUITING

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, 33146, United States

RECRUITING

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, 33442, United States

RECRUITING

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

RECRUITING

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

RECRUITING

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

Rush MD Anderson Cancer Center

Chicago, Illinois, 60612, United States

RECRUITING

Southern Illinois University School of Medicine

Springfield, Illinois, 62702, United States

SUSPENDED

Springfield Memorial Hospital

Springfield, Illinois, 62781, United States

SUSPENDED

Heartland Oncology and Hematology LLP

Council Bluffs, Iowa, 51503, United States

SUSPENDED

Methodist Jennie Edmundson Hospital

Council Bluffs, Iowa, 51503, United States

RECRUITING

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

RECRUITING

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

RECRUITING

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, 66205, United States

RECRUITING

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

RECRUITING

The James Graham Brown Cancer Center at University of Louisville

Louisville, Kentucky, 40202, United States

SUSPENDED

LSU Health Sciences Center at Shreveport

Shreveport, Louisiana, 71103, United States

SUSPENDED

Boston Medical Center

Boston, Massachusetts, 02118, United States

SUSPENDED

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

RECRUITING

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

Henry Ford Hospital

Detroit, Michigan, 48202, United States

RECRUITING

Weisberg Cancer Treatment Center

Farmington Hills, Michigan, 48334, United States

RECRUITING

Henry Ford Medical Center-Columbus

Novi, Michigan, 48377, United States

RECRUITING

Henry Ford West Bloomfield Hospital

West Bloomfield, Michigan, 48322, United States

RECRUITING

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

SSM Health Saint Louis University Hospital

St Louis, Missouri, 63104, United States

RECRUITING

Nebraska Cancer Specialists/Oncology Hematology West PC - MECC

Omaha, Nebraska, 68114, United States

RECRUITING

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

RECRUITING

Oncology Associates PC

Omaha, Nebraska, 68114, United States

SUSPENDED

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire, 03756, United States

RECRUITING

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Saint Barnabas Medical Center

Livingston, New Jersey, 07039, United States

RECRUITING

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

RECRUITING

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

RECRUITING

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester

East White Plains, New York, 10604, United States

RECRUITING

Northwell Health/Center for Advanced Medicine

Lake Success, New York, 11042, United States

ACTIVE NOT RECRUITING

NYU Langone Hospital - Long Island

Mineola, New York, 11501, United States

RECRUITING

Long Island Jewish Medical Center

New Hyde Park, New York, 11040, United States

ACTIVE NOT RECRUITING

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

RECRUITING

Manhattan Eye Ear and Throat Hospital

New York, New York, 10065, United States

ACTIVE NOT RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Lenox Hill Hospital

New York, New York, 10075, United States

ACTIVE NOT RECRUITING

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

RECRUITING

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Sanford Broadway Medical Center

Fargo, North Dakota, 58122, United States

SUSPENDED

Sanford Roger Maris Cancer Center

Fargo, North Dakota, 58122, United States

SUSPENDED

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Clackamas Radiation Oncology Center

Clackamas, Oregon, 97015, United States

RECRUITING

Providence Newberg Medical Center

Newberg, Oregon, 97132, United States

SUSPENDED

Providence Portland Medical Center

Portland, Oregon, 97213, United States

RECRUITING

Providence Saint Vincent Medical Center

Portland, Oregon, 97225, United States

RECRUITING

Carlisle Regional Cancer Center

Carlisle, Pennsylvania, 17015, United States

RECRUITING

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

RECRUITING

UPMC Hillman Cancer Center Erie

Erie, Pennsylvania, 16505, United States

RECRUITING

UPMC Pinnacle Cancer Center/Community Osteopathic Campus

Harrisburg, Pennsylvania, 17109, United States

RECRUITING

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

RECRUITING

UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion

Mechanicsburg, Pennsylvania, 17050, United States

RECRUITING

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

ACTIVE NOT RECRUITING

UPMC-Magee Womens Hospital

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

UPMC-Shadyside Hospital

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

UPMC Memorial

York, Pennsylvania, 17408, United States

RECRUITING

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

Sanford Cancer Center Oncology Clinic

Sioux Falls, South Dakota, 57104, United States

SUSPENDED

Avera Cancer Institute

Sioux Falls, South Dakota, 57105, United States

RECRUITING

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, 57117-5134, United States

SUSPENDED

Methodist Hospital

Memphis, Tennessee, 38104, United States

RECRUITING

University of Tennessee Health Science Center

Memphis, Tennessee, 38163, United States

RECRUITING

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

RECRUITING

MD Anderson in The Woodlands

Conroe, Texas, 77384, United States

RECRUITING

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

RECRUITING

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Michael E DeBakey VA Medical Center

Houston, Texas, 77030, United States

RECRUITING

MD Anderson West Houston

Houston, Texas, 77079, United States

RECRUITING

MD Anderson League City

League City, Texas, 77573, United States

RECRUITING

MD Anderson in Sugar Land

Sugar Land, Texas, 77478, United States

RECRUITING

Central Vermont Medical Center/National Life Cancer Treatment

Berlin Corners, Vermont, 05602, United States

RECRUITING

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

RECRUITING

University of Vermont and State Agricultural College

Burlington, Vermont, 05405, United States

RECRUITING

Froedtert Menomonee Falls Hospital

Menomonee Falls, Wisconsin, 53051, United States

RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Froedtert and MCW Moorland Reserve Health Center

New Berlin, Wisconsin, 53151, United States

RECRUITING

Drexel Town Square Health Center

Oak Creek, Wisconsin, 53154, United States

RECRUITING

Froedtert West Bend Hospital/Kraemer Cancer Center

West Bend, Wisconsin, 53095, United States

RECRUITING

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and NeckMouth Neoplasms

Interventions

X-RaysFluorodeoxyglucose F18acetyl-glycyl-asparagyl-glutaminyl-glutamyl-glutaminyl-valyl-seryl-prolyl-leucyl-threonyl-leucyl-leucyl-lysyl-lysyl-tryptophyl-cysteinyl-Alexa Fluoro 680 C2C2-maleimide conjugateNeck DissectionMagnetic Resonance SpectroscopySentinel Lymph Node BiopsyPhotons

Condition Hierarchy (Ancestors)

Carcinoma, Squamous CellCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsHead and Neck NeoplasmsNeoplasms by SiteMouth DiseasesStomatognathic Diseases

Intervention Hierarchy (Ancestors)

Electromagnetic RadiationElectromagnetic PhenomenaMagnetic PhenomenaPhysical PhenomenaRadiationRadiation, IonizingDeoxyglucoseDeoxy SugarsCarbohydratesLymph Node ExcisionSurgical Procedures, OperativeOtorhinolaryngologic Surgical ProceduresSpectrum AnalysisChemistry Techniques, AnalyticalInvestigative TechniquesBiopsyCytodiagnosisCytological TechniquesClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisSpecimen HandlingDiagnostic Techniques, SurgicalElementary ParticlesLightOptical PhenomenaRadiation, Nonionizing

Study Officials

  • Stephen Y Lai

    NRG Oncology

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 26, 2020

First Posted

April 3, 2020

Study Start

September 23, 2020

Primary Completion (Estimated)

April 27, 2031

Study Completion (Estimated)

April 27, 2031

Last Updated

May 4, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will share

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

More information

Locations