Phase II Treatment Stratification Trial Using Neck Dissection-Driven Selection to Improve Quality of Life for Low Risk Patients With HPV+ Oropharyngeal Squamous Cell Cancer

Study Overview
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Brief Summary
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Investigators will determine whether a treatment paradigm of up-front neck dissection, to more accurately pathologically stage patients, minimizing the number of treatment modalities in patients with low risk oropharyngeal squamous cell carcinoma, can improve quality of life.

Detailed Description
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After enrollment, all patients will undergo neck dissection and primary site biopsy. Pathology will be reviewed, and patients will proceed into one of three standard-of-care (SOC) treatment groups. The treatments themselves are not the focus of this study; the focus of this study is quality of life in this population, after a pathology-based treatment plan, to assess the utility of the investigational neck dissection first paradigm. The SOC treatment plans are as follows: Patients with a single lymph node that measures less than six centimeters, have no extracapsular extension in the lymph node, and have no perineural or perivascular invasion of the primary biopsy will undergo transoral surgery of the primary site. Patients who have 2 positive nodes with no extracapsular extension, or have perineural or perivascular invasion of the primary biopsy will undergo radiation. Patients who have extracapsular extension in any number of lymph nodes or in those patients in whom negative margins are unable to be obtained after the completion of transoral surgery will undergo chemoradiation. After completion of therapy (surgical, radiation, or combined modality) patients will be followed closely on an outpatient basis including regular exams, quality of life questionnaires, and interval surveillance imaging as clinically indicated. Swallowing function will also be addressed by videofluoroscopy one year after completion of therapy. Blood/plasma and oral rinses for correlative studies will be collected at 3-month intervals during 3 years of follow up. This study was initially registered as if it were an inter-group comparison; however, the original and consistent intent has been to determine whether a treatment paradigm of neck dissection guided staging as a whole can minimize the number of standard treatment methods used, leading to improved quality of life in low risk patients with HPV+ oropharyngeal squamous cell cancer. Though certain groups are expected to need multimodal definitive treatment downstream of the experimental neck dissection first paradigm, the population must be assessed as one group in this trial to assess the utility of the paradigm.

Official Title
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Phase II Treatment Stratification Trial Using Neck Dissection-Driven Selection to Improve Quality of Life for Low Risk Patients With HPV+ Oropharyngeal Squamous Cell Cancer

Conditions
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Oropharyngeal Squamous Cell Cancer

Intervention / Treatment
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* Procedure: Neck Dissection
* Procedure: Standard-of-Care (SOC) Transoral Surgery of Primary Site
* Radiation: SOC Radiation
* Drug: SOC Carboplatin
* Drug: SOC Paclitaxel
* Procedure: Videofluoroscopy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have pathologically-confirmed, previously untreated, p16-positive oropharyngeal squamous cell carcinoma Patients must have pretreatment neck and chest imaging Tumors must be potentially surgically resectable via a transoral approach, at the discretion of the treating surgeon Patients with T stage T1-3 Patients with N stage N0-N2c ECOG (Eastern Cooperative Oncology Group Performance Status: an attempt to quantify cancer patients' general well-being and activities of daily life. The score ranges from 0 to 5 where 0 is asymptomatic and 5 is death.) Performance status 0-2 Patients are adults (Age >18) Patients must agree to biospecimen submission for tissue and serum processing and storage for secondary biomarker studies Patients must give documented informed consent to participate in this study. Patients must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry, for the duration of chemoradiation (treatment) and for 3 months after discontinuing treatment. Women of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to starting treatment. Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing and for 30 days after study treatment. Women not of childbearing potential will be defined as all women older than age 50 and anovulatory for 12 months. Sexually active males must use a condom during intercourse while receiving chemoradiation and for 90 days after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid. Likewise, male subjects should not donate sperm during the time they are receiving chemoradiation and for 90 days after stopping treatment. Exclusion Criteria: Prior head and neck radiation or prior chemotherapy for HNSCC (Head and Neck Squamous Cell Carcinoma) Patients with T4 disease Patients with N3 disease FNA evidence of squamous cell carcinoma involving 3 or more lymph nodes Patients with matted lymph nodes, defined as three nodes abutting one another with loss of intervening fat plane that is a replaced with radiologic evidence of extracapsular spread Patients with an outside primary site biopsy showing perineural or perivascular invasion Documented evidence of distant metastases. Active infection Patients residing in prison. Age < 18 years Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification Unstable angina or a history of myocardial ischemia within prior 6 months Patients with any of the following laboratory values at baseline: Absolute neutrophil count (ANC) < 1,000/mm3 Platelets < 75,000/mm3 Hemoglobin < 9.0 gm/dL Calculated or measured creatinine clearance (method determined by the prescribing physicians) < 50 ml/min Bilirubin > 1.5 x ULN (Upper Limit of Normal), except for patients with known Gilbert syndrome who are excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN Aspartate transaminase (AST) > 3.0 x ULN Alanine transaminase (ALT) > 3.0 x ULN Pregnancy or breastfeeding female. Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neck Dissection<br>Patients undergo up-front neck dissection of the cervical lymph nodes to determine stratification into one of three standard-of-care treatment groups: transoral surgery of the primary site, radiation or chemoradiation. | Procedure: Neck Dissection<br>* All patients will undergo neck dissection of the cervical lymph nodes<br>Procedure: Standard-of-Care (SOC) Transoral Surgery of Primary Site<br>* Patients with a single lymph node that measures less than six centimeters, have no extracapsular extension in the lymph node, and have no perineural or perivascular invasion of the primary biopsy will undergo transoral surgery of the primary site.<br>Radiation: SOC Radiation<br>* Patients who have 2 positive nodes with no extracapsular extension, or have perineural or perivascular invasion of the primary biopsy will undergo radiation.<br>Drug: SOC Carboplatin<br>* Patients who have extracapsular extension in any number of lymph nodes or in those patients in whom negative margins are unable to be obtained after the completion of transoral surgery will undergo chemoradiation (Radiation, Carboplatin and Paclitaxel).<br>Drug: SOC Paclitaxel<br>* Patients who have extracapsular extension in any number of lymph nodes or in those patients in whom negative margins are unable to be obtained after the completion of transoral surgery will undergo chemoradiation (Radiation, Carboplatin and Paclitaxel).<br>Procedure: Videofluoroscopy<br>* All patients undergo a videofluoroscopy procedure one year after completion of therapy to assess swallowing function.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Change in Quality of Life (QOL) From Baseline to 12 Months Post Treatment | Four QOL instruments will be administered: the University of Washington Quality of Life (UWQOL), University of Michigan Head and Neck Quality of Life Instrument (HN-QOL), the University of Michigan Voice Related Quality of Life Measure (V-RQOL), and the FACT Head and Neck (version 4) (FACT H&N). Results of each of the 4 surveys will be reported in separate rows in the results table. The difference in scores from baseline to 12 months after completion of study treatment is calculated for each participant, with the median across all participants reported for each survey. Higher scores indicate better QOLs. Range for Questionnaires: HN QOLs: -100 to +100 VR QOLs: -100 to +100 UW QOLs: -100 to +100 FACTHN Physical: -28 to +28 FACTHN Social: -28 to +28 FACTHN Emotional: -24 to +24 FACTHN Functional: -28 to +28 FACTHN subscale: -40 to +40 FACTHN Total: -148 to +148 | Baseline to 12 Months post-treatment (up to approximately 15 months post neck dissection). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of Neck Dissection on Shoulder Function Using the Neck Dissection Impairment Index | The neck dissection impairment index will be scored and summarized for all patients who receive neck dissection. Scores ranging from 0-100 with higher scores indicating better function | 2 years post-treatment (up to approximately 27 months post neck dissection) | 
| Median Change in Quality of Life (QOL) From Baseline to 24 Months Post Treatment | Four QOL instruments will be administered: the University of Washington Quality of Life (UWQOL), University of Michigan Head and Neck Quality of Life Instrument (HN-QOL), the University of Michigan Voice Related Quality of Life Measure (V-RQOL), and the FACT Head and Neck (version 4) (FACT H&N). Results of each of the 4 surveys will be reported in separate rows in the results table. The difference in scores from baseline to 24 months after completion of study treatment is calculated for each participant, with the median across all participants reported for each survey. Higher scores indicate better QOLs. Range for Questionnaires: HN QOLs: -100 to +100 VR QOLs: -100 to +100 UW QOLs: -100 to +100 FACTHN Physical: -28 to +28 FACTHN Social: -28 to +28 FACTHN Emotional: -24 to +24 FACTHN Functional: -28 to +28 FACTHN subscale: -40 to +40 FACTHN Total: -148 to +148 | 2 years post-treatment (up to approximately 27 months post neck dissection) | 
| Disease Specific Survival (DSS) | Proportion of patients alive at 3 years from date of neck dissection. Death from OPSCC (Oropharyngeal Squamous Cell Cancer) will be considered an event for DSS. Death from other causes will be censored at time of death. | 3 Years | 
| Progression Free Survival (PFS) | Proportion of patients alive and free of disease persistence, progression or recurrence at 3 years from the date of completion of study treatment. Persistent disease at completion of treatment, post-treatment recurrence or disease specific death will be defined events for progression free survival (PFS). | 3 Years | 
| Overall Survival (OS) | Proportion of patients alive at 3 years from date of neck dissection. Death from any cause will be considered an event for overall survival. | 3 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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head and neck neoplasms, HPV, human papilloma virus, de-escalation, low-risk, oropharyngeal cancer