Comparing Sentinel Lymph Node (SLN) Biopsy With Standard Neck Dissection for Patients With 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

Overview

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

• Procedure Chest Radiography
  Undergo chest x-ray
• Procedure Computed Tomography
  Undergo SPECT/CT scan and FDG PET/CT or CT
• Other Fludeoxyglucose F-18
  Undergo FDG PET/CT
• Drug Imaging Agent
  Receive imaging agent via injection
• Procedure Neck Dissection
  Undergo standard elective neck dissection
• Procedure Planar Imaging
  Undergo planar imaging
• Procedure Positron Emission Tomography
  Undergo FDG PET/CT
• Other Questionnaire Administration
  Ancillary studies
• Procedure Sentinel Lymph Node Biopsy
  Undergo SLN biopsy
• Procedure Single Photon Emission Computed Tomography
  Undergo SPECT/CT scan

Primary outcome measures

• Patient-reported neck and shoulder function (Phase II/III) [Time frame: Before surgery (Baseline), 3 weeks after surgery, 3, 6, 12 months after surgery]
• Patient reported quality of life (QOL) (Phase II) [Time frame: Before surgery (Baseline), 3 weeks after surgery, 3, 6, 12 months after surgery]
• Disease-free survival (DFS) (phase III) [Time frame: From randomization to local/regional recurrence, distant metastasis, or death due to any cause, whichever comes first, assessed up to 11 years]

Secondary outcome measures (11)

• Overall survival rate [Time frame: From randomization to death due to any cause, assessed up to 11 years]
• Loco-regional failure [Time frame: 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]
• Distant metastasis [Time frame: 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]
• Toxicity [Time frame: Time of primary endpoint analysis]
• Patient-reported shoulder-related QOL, function impairment and disability [Time frame: Baseline, 3 weeks, 3, 6, 12 months post-surgery]
• General quality of life [Time frame: Baseline, 3 weeks, 3, 6, 12 months post-surgery]
• Nodal metastasis detection rate [Time frame: At time of surgery]
• Pathologic false omission rate [Time frame: At time of surgery]
• Length of hospital stay [Time frame: Prior to surgery, at time of discharge from surgery]
• Post-surgery patient-reported outcome [Time frame: At 6 months post-surgery]
• Diagnostic performance (Phase II only) [Time frame: Up to 11 years]

Eligibility 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 106 centers

• University of Alabama at Birmingham Cancer Center — Birmingham
• Banner MD Anderson Cancer Center — Gilbert
• Mayo Clinic Hospital in Arizona — Phoenix
• Banner University Medical Center - Tucson — Tucson
• University of Arizona Cancer Center-North Campus — Tucson
• University of Arkansas for Medical Sciences — Little Rock
• City of Hope Comprehensive Cancer Center — Duarte
• UC San Diego Moores Cancer Center — La Jolla
• … and 98 more centers

Canada · 1 center

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT04333537 · NRG-HN006 · NCI-2020-01542 · NRG-HN006 · NRG-HN006 · U10CA180868

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗