Comparing Sentinel Lymph Node (SLN) Biopsy With Standard Neck Dissection for Patients With Early-Stage Oral Cavity Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
|
Phase 2/Phase 3 |
Detailed Description
PRIMARY OBJECTIVES:
- 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)
- 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:
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To compare patterns of failure (local-regional relapse and distant metastasis) between surgical arms.
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To measure and compare overall survival (OS) between surgical arms. III. To measure and compare the toxicity of the two surgical arms.
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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.
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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.
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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:
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To compare changes in patient-reported outcomes (European Quality of Life Five Dimension Five Level Scale Questionnaire [EQ-5D-5L]) between surgical arms.
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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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Sentinel Lymph Node (SLN) Biopsy Patients receive an imaging agent via injection and undergo planar imaging and SPECT/CT over 1-2 hours. Patients then undergo SLN biopsy. |
Procedure: Computed Tomography (CT)
Undergo SPECT/CT scan
Other Names:
Drug: Imaging Agent
Receive imaging agent via injection
Other Names:
Procedure: Planar Imaging
Undergo planar imaging
Procedure: Sentinel Lymph Node Biopsy
Undergo SLN biopsy
Other Names:
Procedure: Single Photon Emission Computed Tomography
Undergo SPECT/CT scan
Other Names:
|
| Active Comparator: Elective Neck Dissection (END) Patients undergo standard END. |
Procedure: Computed Tomography (CT)
Undergo SPECT/CT scan
Other Names:
Procedure: Neck Dissection
Undergo standard elective neck dissection
|
Outcome Measures
Primary Outcome Measures
- Patient-reported neck and shoulder function (Phase II/III) [From Baseline (Before surgery) to 6 months post-surgery]
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.
- Disease-Free Survival [From randomization to local/regional recurrence, distant metastasis, or death due to any cause, whichever comes first, assessed up to 11 years]
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.
Secondary Outcome Measures
- Overall Survival [From randomization to death due to any cause, assessed up to 11 years]
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.
- 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]
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.
- 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]
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.
- Patient-reported shoulder-related QOL, function impairment and disability [Baseline, 3 weeks, 3, 6, 12 months post-surgery. Analysis occurs at the same time as the primary endpoint.]
Patient reported using Abbreviated Disabilities of the Arm, Shoulder, and Hand (QuickDASH) with scores of 0-100. A higher score indicates greater disability.
- General quality of life [Baseline, 3 weeks, 3, 6, 12 months post-surgery. Analysis occurs at the same time as the primary endpoint.]
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.
- Nodal metastasis detection rate [During surgery. Analysis occurs at the same time as the primary endpoint.]
Defined as the proportion of patients with pathologic positive nodes using the pathology results.
- Pathologic false omission rate [During surgery. Analysis occurs at the same time as the primary endpoint.]
Measured within the sentinel lymph node biopsy (SLN) arm only. Defined as the proportion of patients with false negative results among negative SLN patients.
- Post-surgery patient-reported outcome [At 6 months post-surgery. Analysis occurs at the same time as the primary endpoint.]
Measured by NDII in low-risk oral cavity squamous cell carcinoma patients using ANCOVA comparison model.
Eligibility Criteria
Criteria
Inclusion Criteria:
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PRIOR TO STEP 1 REGISTRATION INCLUSION:
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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
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Appropriate stage for study entry (T1-2N0M0; American Joint Committee on Cancer [AJCC] 8th edition [ed.]) based on the following diagnostic workup:
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History/physical examination within 42 days prior to registration
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Imaging of head and neck within 42 days prior to registration
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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.
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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)
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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)
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Surgical resection of the primary tumor will occur through a transoral approach with anticipation of resection free margins
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Zubrod performance status 0-2 within 42 days prior to registration
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For women of child-bearing potential, negative serum or urine pregnancy test within 42 days prior to registration
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The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
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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
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PRIOR TO STEP 2 RANDOMIZATION:
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FDG PET/CT required prior to step 2. Note: FDG PET/CT done prior to step 1 can be submitted for central review.
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PET/CT node negative patients, determined by central read, will proceed to randomization.
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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
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NOTE: All FDG PET/CT scans must be performed on an American College of Radiology (ACR) accredited scanner (or similar accrediting organization)
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The patient must complete NDII prior to step 2 registration
Exclusion Criteria:
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PRIOR TO STEP 1 REGISTRATION EXCLUSION:
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Definitive clinical or radiologic evidence of regional (cervical) and/or distant metastatic disease
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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
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Diagnosis of head and neck squamous cell carcinoma (SCC) in the oropharynx, nasopharynx, hypopharynx, and larynx
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Unable or unwilling to complete NDII (baseline only)
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Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
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Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
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Patient with severe, active co-morbidity that would preclude an elective or completion neck dissection
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Pregnancy and breast-feeding mothers
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Incomplete resection of oral cavity lesion with a positive margin; however, an excisional biopsy is permitted
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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
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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)
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Actively receiving systemic cytotoxic chemotherapy, immunosuppressive, anti-monocyte or immunomodulatory therapy
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Currently participating in another investigational therapeutic trial
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Banner University Medical Center - Tucson | Tucson | Arizona | United States | 85719 |
| 2 | University of Arizona Cancer Center-North Campus | Tucson | Arizona | United States | 85719 |
| 3 | University of Arkansas for Medical Sciences | Little Rock | Arkansas | United States | 72205 |
| 4 | City of Hope Comprehensive Cancer Center | Duarte | California | United States | 91010 |
| 5 | UC San Diego Moores Cancer Center | La Jolla | California | United States | 92093 |
| 6 | Stanford Cancer Institute Palo Alto | Palo Alto | California | United States | 94304 |
| 7 | University of California Davis Comprehensive Cancer Center | Sacramento | California | United States | 95817 |
| 8 | UM Sylvester Comprehensive Cancer Center at Coral Gables | Coral Gables | Florida | United States | 33146 |
| 9 | UM Sylvester Comprehensive Cancer Center at Deerfield Beach | Deerfield Beach | Florida | United States | 33442 |
| 10 | University of Miami Miller School of Medicine-Sylvester Cancer Center | Miami | Florida | United States | 33136 |
| 11 | Emory University Hospital Midtown | Atlanta | Georgia | United States | 30308 |
| 12 | Emory University Hospital/Winship Cancer Institute | Atlanta | Georgia | United States | 30322 |
| 13 | Northwestern University | Chicago | Illinois | United States | 60611 |
| 14 | Rush University Medical Center | Chicago | Illinois | United States | 60612 |
| 15 | Southern Illinois University School of Medicine | Springfield | Illinois | United States | 62702 |
| 16 | Memorial Medical Center | Springfield | Illinois | United States | 62781 |
| 17 | University of Iowa/Holden Comprehensive Cancer Center | Iowa City | Iowa | United States | 52242 |
| 18 | University of Kansas Cancer Center | Kansas City | Kansas | United States | 66160 |
| 19 | University of Kansas Hospital-Westwood Cancer Center | Westwood | Kansas | United States | 66205 |
| 20 | University of Kentucky/Markey Cancer Center | Lexington | Kentucky | United States | 40536 |
| 21 | The James Graham Brown Cancer Center at University of Louisville | Louisville | Kentucky | United States | 40202 |
| 22 | LSU Health Sciences Center at Shreveport | Shreveport | Louisiana | United States | 71103 |
| 23 | University of Michigan Comprehensive Cancer Center | Ann Arbor | Michigan | United States | 48109 |
| 24 | Wayne State University/Karmanos Cancer Institute | Detroit | Michigan | United States | 48201 |
| 25 | Henry Ford Hospital | Detroit | Michigan | United States | 48202 |
| 26 | Weisberg Cancer Treatment Center | Farmington Hills | Michigan | United States | 48334 |
| 27 | Nebraska Cancer Specialists/Oncology Hematology West PC - MECC | Omaha | Nebraska | United States | 68114 |
| 28 | Nebraska Methodist Hospital | Omaha | Nebraska | United States | 68114 |
| 29 | Oncology Associates PC | Omaha | Nebraska | United States | 68114 |
| 30 | Memorial Sloan Kettering Basking Ridge | Basking Ridge | New Jersey | United States | 07920 |
| 31 | Saint Barnabas Medical Center | Livingston | New Jersey | United States | 07039 |
| 32 | Memorial Sloan Kettering Monmouth | Middletown | New Jersey | United States | 07748 |
| 33 | Memorial Sloan Kettering Bergen | Montvale | New Jersey | United States | 07645 |
| 34 | Rutgers Cancer Institute of New Jersey | New Brunswick | New Jersey | United States | 08903 |
| 35 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14263 |
| 36 | Memorial Sloan Kettering Commack | Commack | New York | United States | 11725 |
| 37 | Memorial Sloan Kettering Westchester | Harrison | New York | United States | 10604 |
| 38 | Laura and Isaac Perlmutter Cancer Center at NYU Langone | New York | New York | United States | 10016 |
| 39 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
| 40 | Memorial Sloan Kettering Nassau | Uniondale | New York | United States | 11553 |
| 41 | Sanford Broadway Medical Center | Fargo | North Dakota | United States | 58122 |
| 42 | Sanford Roger Maris Cancer Center | Fargo | North Dakota | United States | 58122 |
| 43 | Cleveland Clinic Foundation | Cleveland | Ohio | United States | 44195 |
| 44 | Ohio State University Comprehensive Cancer Center | Columbus | Ohio | United States | 43210 |
| 45 | University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | United States | 73104 |
| 46 | Clackamas Radiation Oncology Center | Clackamas | Oregon | United States | 97015 |
| 47 | Providence Newberg Medical Center | Newberg | Oregon | United States | 97132 |
| 48 | Providence Portland Medical Center | Portland | Oregon | United States | 97213 |
| 49 | Providence Saint Vincent Medical Center | Portland | Oregon | United States | 97225 |
| 50 | Geisinger Medical Center | Danville | Pennsylvania | United States | 17822 |
| 51 | Penn State Milton S Hershey Medical Center | Hershey | Pennsylvania | United States | 17033-0850 |
| 52 | Thomas Jefferson University Hospital | Philadelphia | Pennsylvania | United States | 19107 |
| 53 | Fox Chase Cancer Center | Philadelphia | Pennsylvania | United States | 19111 |
| 54 | University of Pittsburgh Cancer Institute (UPCI) | Pittsburgh | Pennsylvania | United States | 15232 |
| 55 | UPMC-Shadyside Hospital | Pittsburgh | Pennsylvania | United States | 15232 |
| 56 | Sanford Cancer Center Oncology Clinic | Sioux Falls | South Dakota | United States | 57104 |
| 57 | Avera Cancer Institute | Sioux Falls | South Dakota | United States | 57105 |
| 58 | Sanford USD Medical Center - Sioux Falls | Sioux Falls | South Dakota | United States | 57117-5134 |
| 59 | Vanderbilt University/Ingram Cancer Center | Nashville | Tennessee | United States | 37232 |
| 60 | MD Anderson in The Woodlands | Conroe | Texas | United States | 77384 |
| 61 | Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center | Houston | Texas | United States | 77030 |
| 62 | M D Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 63 | Michael E DeBakey VA Medical Center | Houston | Texas | United States | 77030 |
| 64 | MD Anderson West Houston | Houston | Texas | United States | 77079 |
| 65 | MD Anderson League City | League City | Texas | United States | 77573 |
| 66 | MD Anderson in Sugar Land | Sugar Land | Texas | United States | 77478 |
| 67 | Central Vermont Medical Center/National Life Cancer Treatment | Berlin | Vermont | United States | 05602 |
| 68 | University of Vermont Medical Center | Burlington | Vermont | United States | 05401 |
| 69 | University of Vermont and State Agricultural College | Burlington | Vermont | United States | 05405 |
| 70 | University Health Network-Princess Margaret Hospital | Toronto | Ontario | Canada | M5G 2M9 |
Sponsors and Collaborators
- NRG Oncology
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Stephen Y Lai, NRG Oncology
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NRG-HN006
- NCI-2020-01542
- NRG-HN006
- NRG-HN006
- U10CA180868