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
| Phase | Phase2; Phase3 |
|---|---|
| Study type | Interventional |
| Ages | 18 Years and up |
| Sex | All |
| Enrollment | 686 (estimated) |
| Sponsor | NRG Oncology Academic / other |
| Drugs / interventions | chemotherapy, radiation |
| Locations | 107 sites (Birmingham, Alabama and 106 other locations) |
| Status | Recruiting |
| Started | September 23, 2020 |
| Main results expected | April 27, 2031 |
| Study ends | April 27, 2036 |
| Registry record updated | August 17, 2026 |
| Trial ID | NCT04333537 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
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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
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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.
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Personalized neck radiation guided by sentinel lymph node biopsy for oral cavity cancer
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Adding BMX-001, a drug that protects normal tissue from radiation damage, to standard chemoradiation for head and neck cancer
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Proton or Photon Radiotherapy Added to Pembrolizumab Before Surgery for Advanced or Recurrent Oral Cavity Cancer
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Selective neck dissection (levels I–IV) vs. modified neck dissection (levels I–V) in oral cavity cancer with a positive neck
This trial tests whether a less extensive neck surgery can control cancer as well as the standard broader surgery in patients with one involved neck node from oral cavity cancer.
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EVOLVE104 for advanced bladder and other squamous cell cancers
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Adding chemotherapy or chemo-immunotherapy to standard salvage surgery for advanced head and neck cancer
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How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.