Buccal Mucosa Squamous Cell Carcinoma, Floor of Mouth Squamous Cell Carcinoma, Gingival Squamous Cell Carcinoma, Hard Palate Squamous Cell Carcinoma, Lip Squamous Cell Carcinoma, Lower Alveolar Ridge Squamous Cell Carcinoma, Oral Cavity Squamous Cell Carcinoma, Retromolar Trigone Squamous Cell Carcinoma, 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
Conditions
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.
Detailed 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 (PET)/computed tomography (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 using the NDII and related QOL at 6 months after surgery with SLN biopsy is superior to the END in low-risk patients. X. To compare the diagnostic performance of planar only versus (vs.) single photon emission computed tomography (SPECT)/CT plus planar for SLN mapping (phase II only). 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 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. GROUP II: Patients undergo standard END. Patients also undergo FDG PET/CT, CT, and/or chest x-ray at screening and during follow up. 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.
Interventions
PROCEDUREChest Radiography
Undergo chest x-ray
PROCEDUREComputed Tomography
Undergo SPECT/CT scan and FDG PET/CT or CT
OTHERFludeoxyglucose F-18
Undergo FDG PET/CT
DRUGImaging Agent
Receive imaging agent via injection
PROCEDURENeck Dissection
Undergo standard elective neck dissection
PROCEDUREPlanar Imaging
Undergo planar imaging
PROCEDUREPositron Emission Tomography
Undergo FDG PET/CT
OTHERQuestionnaire Administration
Ancillary studies
PROCEDURESentinel Lymph Node Biopsy
Undergo SLN biopsy
PROCEDURESingle Photon Emission Computed Tomography
Undergo SPECT/CT scan
Sponsors
NRG Oncology
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patient-reported neck and shoulder function (Phase II/III) | Before surgery (Baseline), 3 weeks after surgery, 3, 6, 12 months after 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 between arm difference in the 6-month post-surgery NDII scores is clinically meaningful. |
| Patient reported quality of life (QOL) (Phase II) | Before surgery (Baseline), 3 weeks after surgery, 3, 6, 12 months after surgery | Will be measured using 3 questionnaires over 12-15 minutes. |
| Disease-free survival (DFS) (phase III) | From randomization to local/regional recurrence, distant metastasis, or death due to any cause, whichever comes first, assessed up to 11 years | Measured using Cox proportional hazards model and the Kaplan-Meier method. Failure includes local/regional recurrence, distant metastasis, or death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival rate | From randomization to death due to any cause, assessed up to 11 years | 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 | The cumulative incidence estimator will be used to estimate time to event distributions with between arm differences 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 | The cumulative incidence estimator will be used to estimate event distributions with between arm differences tested using cause-specific log-rank test. |
| Toxicity | Time of primary endpoint analysis | Measured by the Common Terminology Criteria for Adverse Events version 5.0. The proportion of patients with at least 1 grade 3 or higher adverse event will be compared between treatment arms. |
| Patient-reported shoulder-related QOL, function impairment and disability | Baseline, 3 weeks, 3, 6, 12 months post-surgery | 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 | Will be measured using the Functional Assessment of Cancer Therapy-Head and Neck to measure Functional Assessment of Cancer Therapy-Head and Neck-Trial Outcome Index scores on a scale from 0-96. A higher score indicates better quality of life. |
| Nodal metastasis detection rate | At time of surgery | Defined as the proportion of patients with pathologic positive nodes using the pathology results. |
| Pathologic false omission rate | At time of surgery | Measured within the sentinel lymph node biopsy (SLN) arm only. Defined as the proportion of patients with false negative results among negative SLN patients. |
| Length of hospital stay | Prior to surgery, at time of discharge from surgery | Length of hospital stay due to surgical procedure will be compared between arms using the Mann-Whitney test. |
| Post-surgery patient-reported outcome | At 6 months post-surgery | Measured by NDII in low-risk oral cavity squamous cell carcinoma patients using analysis of covariance comparison model. |
| Diagnostic performance (Phase II only) | Up to 11 years | Descriptive statistics (minimum, maximum, mean, standard deviation, and coefficient of variation) of the number of detected SLNs will be calculated by modality and neck sublevel. The difference of the number of SLNs between single photon emission computed tomography/computed tomography plus planar and planar only will be computed and summarized by neck sublevel, reader, and overall. Pairwise absolute differences of the number of detected SLNs among readers will be computed and summarized by modality and neck sublevel. |
Countries
Canada, United States
Contacts
PRINCIPAL_INVESTIGATORStephen Y Lai
NRG Oncology
Outcome results
None listed