Comparing Sentinel Lymph Node (SLN) Biopsy With Standard Neck Dissection for Patients With Early-Stage Oral Cavity Cancer

Oral Cavity Squamous Cell Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04333537
• Other study ID #: NRG-HN006
• Secondary ID: NCI-2020-01542NR
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: July 8, 2020
• Est. completion date: May 18, 2036

Study information

• Verified date: February 2024
• Source: NRG Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

PRIMARY OBJECTIVES:

I. To determine if patient-reported neck and shoulder function and related quality of life (QOL) at 6 months after surgery using the Neck Dissection Impairment Index (NDII) is superior with sentinel lymph node (SLN) biopsy compared to elective neck dissection (END) for treatment of early-stage oral cavity squamous cell carcinoma (OCSCC) (cT1-2N0). (Phase II) II. To determine if disease-free survival (DFS) is non-inferior with SLN biopsy compared to END for treatment of early-stage OCSCC (cT1-2N0). (Phase III) III. To determine if patient-reported neck and shoulder function and related QOL at 6 months after surgery using NDII is superior with SLN biopsy compared to END for treatment of early-stage OCSCC (cT1-2N0). (Phase III)

SECONDARY OBJECTIVES:

I. To compare patterns of failure (local-regional relapse and distant metastasis) between surgical arms.

II. To measure and compare overall survival (OS) between surgical arms. III. To measure and compare the toxicity of the two surgical arms.

IV. To measure longitudinal patient-reported neck and shoulder function and related QOL between surgical arms, using the following instruments:

IVa. Neck Dissection Impairment Index (NDII). IVb. Abbreviated Disabilities of the Arm, Shoulder and Hand (QuickDASH). IVc. Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N). V. To assess the length of hospitalization, post-operative drain placement, and operative morbidity between arms.

VI. To estimate the negative predictive rate of fludeoxyglucose F-18 (FDG)-positron emission tomography/computed tomography (PET/CT) for N0 neck in patients with T1 and T1-2 oral cavity squamous cell cancer (OCSCC) patients in the END arm.

VII. To assess nodal metastases rates between arms. VIII. To assess the pathologic false omission rate (FOR) in the SLN biopsy arm. IX. To determine if patient-reported neck and shoulder function and related QOL at 6 months after surgery using the NDII is superior with the SLN biopsy compared to the END in low-risk patients.

EXPLORATORY OBJECTIVES:

I. To compare changes in patient-reported outcomes (European Quality of Life Five Dimension Five Level Scale Questionnaire [EQ-5D-5L]) between surgical arms.

II. To collect biospecimens for future translational science studies. III. To assess the DFS between arms in low-risk patients.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP I: Patients receive an imaging agent via injection and undergo planar imaging and single photo emission computed tomography/computed tomography (SPECT/CT) over 1-2 hours. Patients then undergo SLN biopsy.

GROUP II: Patients undergo standard END.

After completion of study treatment, patients are followed up 3 weeks after surgery, every 3 months for year 1, every 4 months for year 2, every 6 months for year 3, then yearly thereafter.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 618
• Est. completion date: May 18, 2036
• Est. primary completion date: May 18, 2031
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• PRIOR TO STEP 1 REGISTRATION INCLUSION:

• Pathologically (histologically or cytologically) proven diagnosis of squamous cell carcinoma 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 for 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

• 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 are eligible to participate as the mandatory patient reported NDII tool is only available in this language

• 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 squamous cell carcinoma (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 a different cancer is allowable

• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields

• Patient with 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-guided (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 (sarcoidosis or untreated mycobacterial infection)

• Actively receiving systemic cytotoxic chemotherapy, immunosuppressive, anti-monocyte or immunomodulatory therapy

• Currently participating in another investigational therapeutic trial

Related Conditions & MeSH terms

• Buccal Mucosa Squamous Cell Carcinoma
• Carcinoma
• Carcinoma, Squamous Cell
• Floor of Mouth Squamous Cell Carcinoma
• Gingival Squamous Cell Carcinoma
• Hard Palate Squamous Cell Carcinoma
• Lip Neoplasms
• Lip Squamous Cell Carcinoma
• Lower Alveolar Ridge Squamous Cell Carcinoma
• Mouth Neoplasms
• Oral Cavity Squamous Cell Carcinoma
• Retromolar Trigone Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck
• Stage I Lip and Oral Cavity Cancer AJCC v8
• Stage II Lip and Oral Cavity Cancer AJCC v8
• Tongue Squamous Cell Carcinoma
• Upper Alveolar Ridge Squamous Cell Carcinoma

Intervention

Procedure:
• Computed Tomography (CT)
Undergo SPECT/CT scan

Drug:
• Imaging Agent
Receive imaging agent via injection

Procedure:
• Neck Dissection
Undergo standard elective neck dissection
• Planar Imaging
Undergo planar imaging
• Sentinel Lymph Node Biopsy
Undergo SLN biopsy
• Single Photon Emission Computed Tomography
Undergo SPECT/CT scan

Locations

Country	Name	City	State
Canada	University Health Network-Princess Margaret Hospital	Toronto	Ontario
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey
United States	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont
United States	Boston Medical Center	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of Vermont and State Agricultural College	Burlington	Vermont
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Memorial Sloan Kettering Commack	Commack	New York
United States	MD Anderson in The Woodlands	Conroe	Texas
United States	UM Sylvester Comprehensive Cancer Center at Coral Gables	Coral Gables	Florida
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	UM Sylvester Comprehensive Cancer Center at Deerfield Beach	Deerfield Beach	Florida
United States	Henry Ford Hospital	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas
United States	M D Anderson Cancer Center	Houston	Texas
United States	MD Anderson West Houston	Houston	Texas
United States	Michael E DeBakey VA Medical Center	Houston	Texas
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Northwell Health/Center for Advanced Medicine	Lake Success	New York
United States	MD Anderson League City	League City	Texas
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	The James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky
United States	Methodist Hospital	Memphis	Tennessee
United States	University of Tennessee Health Science Center	Memphis	Tennessee
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Memorial Sloan Kettering Monmouth	Middletown	New Jersey
United States	NYU Winthrop Hospital	Mineola	New York
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Yale University	New Haven	Connecticut
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	Lenox Hill Hospital	New York	New York
United States	Manhattan Eye Ear and Throat Hospital	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Cancer Specialists/Oncology Hematology West PC - MECC	Omaha	Nebraska
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Oncology Associates PC	Omaha	Nebraska
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	UPMC-Shadyside Hospital	Pittsburgh	Pennsylvania
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Stanford Cancer Center South Bay	San Jose	California
United States	LSU Health Sciences Center at Shreveport	Shreveport	Louisiana
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Memorial Medical Center	Springfield	Illinois
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	MD Anderson in Sugar Land	Sugar Land	Texas
United States	Smilow Cancer Hospital Care Center-Trumbull	Trumbull	Connecticut
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	University of Arizona Cancer Center-North Campus	Tucson	Arizona
United States	Memorial Sloan Kettering Nassau	Uniondale	New York
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
NRG Oncology	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 (change from Baseline to 6 months) between arm difference is clinically meaningful. The hypothesis of no between-arm difference in 6-month NDII scores will be tested using the ANCOVA model at one-sided significance level of 0.10. Point estimates and 95% confidence intervals (CIs) for the mean NDII scores at 6 months for each treatment arm and for the between-arm difference at 6-months based on the proposed model will be provided.	From Baseline (Before surgery) to 6 months post-surgery
Primary	Disease-Free Survival	An event for disease-free survival is local recurrence, regional recurrence, distant metastasis, or death due to any cause. Disease-free survival time is randomization date to the date of event or last known follow-up (censoring). Rates will be estimated using the Kaplan-Meier method and between-arm differences compared using the log-rank test.	From randomization to local/regional recurrence, distant metastasis, or death due to any cause, whichever comes first, assessed up to 11 years
Secondary	Overall Survival	An event for overall survival is death due to any cause. Overall survival time is randomization date to date of event or last known follow-up (censoring). Rates will be estimated using the Kaplan-Meier method and between-arm differences compared using the log-rank test.	From randomization to death due to any cause, assessed up to 11 years
Secondary	Loco-regional Failure	An event for local-regional failure is local or regional recurrence. Local-regional failure time is randomization date to date of event, precluding event, or last known follow-up (censoring). Rates will be estimated using the cumulative incidence method and between arm differences compared using cause-specific log-rank test.	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
Secondary	Distant metastasis	An event is the occurrence of distant metastasis. Distant metastasis time is randomization to date of event, precluding event, or last known follow-up (censoring). Rates will be estimated using the cumulative incidence method and between-arm differences compared using cause-specific log-rank test.	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
Secondary	Patient-reported shoulder-related QOL, function impairment and disability	Patient reported using Abbreviated Disabilities of the Arm, Shoulder, and Hand (QuickDASH) with scores of 0-100. A higher score indicates greater disability.	Baseline, 3 weeks, 3, 6, 12 months post-surgery. Analysis occurs at the same time as the primary endpoint.
Secondary	General quality of life	Will be measured using the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) to measure Functional Assessment of Cancer Therapy-Head and Neck-Trial Outcome Index (FACT-TOI) scores on a scale from 0-96. A higher score indicates better quality of life.	Baseline, 3 weeks, 3, 6, 12 months post-surgery. Analysis occurs at the same time as the primary endpoint.
Secondary	Nodal metastasis detection rate	Defined as the proportion of patients with pathologic positive nodes using the pathology results.	During surgery. Analysis occurs at the same time as the primary endpoint.
Secondary	Pathologic false omission rate	Measured within the sentinel lymph node biopsy (SLN) arm only. Defined as the proportion of patients with false negative results among negative SLN patients.	During surgery. Analysis occurs at the same time as the primary endpoint.
Secondary	Post-surgery patient-reported outcome	Measured by NDII in low-risk oral cavity squamous cell carcinoma patients using ANCOVA comparison model.	At 6 months post-surgery. Analysis occurs at the same time as the primary endpoint.