Clinical trial Recruiting at 88 sites Phase2; Phase3 Interventional Ages 18 and up

Sentinel lymph node biopsy versus standard neck dissection for early-stage oral cavity cancer

Official title: Randomized Phase II/III Trial of Sentinel Lymph Node Biopsy Versus Elective Neck Dissection for Early-Stage Oral Cavity Cancer

Run by NRG Oncology · NCT04333537 · Data updated 2026-11-12

This trial tests whether removing only the sentinel lymph nodes instead of doing a full neck dissection helps people with early-stage oral cavity cancer have better neck and shoulder function while keeping cancer control the same.

Quick facts

PhasePhase2; Phase3
Study typeInterventional
Ages18 Years and up
SexAll
Enrollment686 (estimated)
SponsorNRG Oncology
Academic / other
Drugs / interventionschemotherapy, radiation
Locations107 sites (Birmingham, Alabama and 106 other locations)
StatusRecruiting
StartedSeptember 23, 2020
Main results expectedApril 27, 2031
Study endsApril 27, 2036
Registry record updatedAugust 17, 2026
Trial IDNCT04333537 on ClinicalTrials.gov

Is this trial a fit for you?

Likely a good fit

Ideal candidates are people with pathologically confirmed early-stage (T1-2N0M0) oral cavity squamous cell carcinoma who are medically fit for surgery and have completed the required diagnostic imaging.

Probably not a fit

Patients with clinically or radiographically node-positive disease, more advanced tumors, or prior head and neck treatments are unlikely to benefit from the SLN approach in this trial.

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This randomized phase II/III trial compares sentinel lymph node (SLN) biopsy to elective neck dissection (END) in patients with early-stage (cT1-2N0M0) oral cavity squamous cell carcinoma. Patients undergo preoperative imaging and SLN mapping with an imaging agent when assigned to the SLN arm, and surgeons remove either mapped sentinel nodes or perform a standard neck dissection per randomization. The phase II component focuses on patient-reported neck and shoulder function at 6 months using the Neck Dissection Impairment Index (NDII), and the phase III component tests non-inferiority for disease-free survival while also measuring quality of life, complications, and survival. Secondary endpoints include patterns of failure, overall survival, treatment toxicity, length of stay, drain use, and longitudinal patient-reported outcomes.

Why it matters

Potential benefit: If successful, patients could experience less neck and shoulder dysfunction, shorter recovery, and fewer surgical complications while maintaining the same cancer control.

How similar studies have gone: Previous single-center and multicenter studies have shown promising accuracy and reduced morbidity with SLN biopsy in early oral cavity cancers, but definitive phase III data are limited.

Who can join: the full rules

Show full inclusion / exclusion criteria
Inclusion Criteria:

* PRIOR TO STEP 1 REGISTRATION INCLUSION:
* 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:
* FDG PET/CT required prior to step 2. Note: FDG PET/CT done prior to step 1 can be submitted for central review

  * PET/CT node negative patients, determined by central read, will proceed to randomization. PET/CT node positive patients will go off study, but will be entered in a registry and data will be collected to record the pathological outcome of neck nodes for diagnostic imaging assessment and future clinical trial development

    * NOTE: All FDG PET/CT scans must be performed on an American College of Radiology (ACR) accredited scanner (or similar accrediting organization)
* The patient must complete NDII prior to step 2 registration

Exclusion Criteria:

* PRIOR TO STEP 1 REGISTRATION EXCLUSION:
* 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

Where it's running

  • Banner MD Anderson Cancer Center
    Gilbert, Arizona, United States
    Recruiting
  • Mayo Clinic Hospital in Arizona
    Phoenix, Arizona, United States
    Recruiting
  • Banner University Medical Center - Tucson
    Tucson, Arizona, United States
    Recruiting
  • University of Arizona Cancer Center-North Campus
    Tucson, Arizona, United States
    Recruiting
  • University of Arkansas for Medical Sciences
    Little Rock, Arkansas, United States
    Recruiting
  • UC San Diego Moores Cancer Center
    La Jolla, California, United States
    Recruiting
Show 44 more locations
  • Stanford Cancer Institute Palo Alto
    Palo Alto, California, United States
    Recruiting
  • UC San Diego Medical Center - Hillcrest
    San Diego, California, United States
    Recruiting
  • UCSF Medical Center-Mission Bay
    San Francisco, California, United States
    Recruiting
  • Stanford Cancer Center South Bay
    San Jose, California, United States
    Recruiting
  • Yale University
    New Haven, Connecticut, United States
    Recruiting
  • Smilow Cancer Hospital Care Center-Trumbull
    Trumbull, Connecticut, United States
    Recruiting
  • UM Sylvester Comprehensive Cancer Center at Coral Gables
    Coral Gables, Florida, United States
    Recruiting
  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach
    Deerfield Beach, Florida, United States
    Recruiting
  • University of Miami Miller School of Medicine-Sylvester Cancer Center
    Miami, Florida, United States
    Recruiting
  • Emory University Hospital Midtown
    Atlanta, Georgia, United States
    Recruiting
  • Emory University Hospital/Winship Cancer Institute
    Atlanta, Georgia, United States
    Recruiting
  • Northwestern University
    Chicago, Illinois, United States
    Recruiting
  • Rush MD Anderson Cancer Center
    Chicago, Illinois, United States
    Recruiting
  • Heartland Oncology and Hematology LLP
    Council Bluffs, Iowa, United States
    Recruiting
  • Methodist Jennie Edmundson Hospital
    Council Bluffs, Iowa, United States
    Recruiting
  • University of Iowa/Holden Comprehensive Cancer Center
    Iowa City, Iowa, United States
    Recruiting
  • University of Kansas Cancer Center
    Kansas City, Kansas, United States
    Recruiting
  • University of Kansas Hospital-Westwood Cancer Center
    Westwood, Kansas, United States
    Recruiting
  • University of Kentucky/Markey Cancer Center
    Lexington, Kentucky, United States
    Recruiting
  • University of Michigan Rogel Cancer Center
    Ann Arbor, Michigan, United States
    Recruiting
  • Wayne State University/Karmanos Cancer Institute
    Detroit, Michigan, United States
    Recruiting
  • Henry Ford Hospital
    Detroit, Michigan, United States
    Recruiting
  • Weisberg Cancer Treatment Center
    Farmington Hills, Michigan, United States
    Recruiting
  • Henry Ford Medical Center-Columbus
    Novi, Michigan, United States
    Recruiting
  • Henry Ford West Bloomfield Hospital
    West Bloomfield, Michigan, United States
    Recruiting
  • Mayo Clinic in Rochester
    Rochester, Minnesota, United States
    Recruiting
  • SSM Health Saint Louis University Hospital
    St Louis, Missouri, United States
    Recruiting
  • Nebraska Cancer Specialists/Oncology Hematology West PC - MECC
    Omaha, Nebraska, United States
    Recruiting
  • Nebraska Methodist Hospital
    Omaha, Nebraska, United States
    Recruiting
  • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
    Lebanon, New Hampshire, United States
    Recruiting
  • Memorial Sloan Kettering Basking Ridge
    Basking Ridge, New Jersey, United States
    Recruiting
  • Saint Barnabas Medical Center
    Livingston, New Jersey, United States
    Recruiting
  • Memorial Sloan Kettering Monmouth
    Middletown, New Jersey, United States
    Recruiting
  • Memorial Sloan Kettering Bergen
    Montvale, New Jersey, United States
    Recruiting
  • Rutgers Cancer Institute of New Jersey
    New Brunswick, New Jersey, United States
    Recruiting
  • Roswell Park Cancer Institute
    Buffalo, New York, United States
    Recruiting
  • Memorial Sloan Kettering Commack
    Commack, New York, United States
    Recruiting
  • Memorial Sloan Kettering Westchester
    Harrison, New York, United States
    Recruiting
  • NYU Langone Hospital - Long Island
    Mineola, New York, United States
    Recruiting
  • Laura and Isaac Perlmutter Cancer Center at NYU Langone
    New York, New York, United States
    Recruiting
  • Memorial Sloan Kettering Cancer Center
    New York, New York, United States
    Recruiting
  • Memorial Sloan Kettering Nassau
    Uniondale, New York, United States
    Recruiting
  • UNC Lineberger Comprehensive Cancer Center
    Chapel Hill, North Carolina, United States
    Recruiting
  • Cleveland Clinic Foundation
    Cleveland, Ohio, United States
    Recruiting

+57 more sites. See ClinicalTrials.gov for the full list.

Study contacts

  • Principal investigator: Stephen Y Lai — NRG Oncology

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

How to take part

  1. Review the eligibility criteria above with your treating physician.
  2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
  3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.
Last reviewed 2026-11-14 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.