Dexamethasone in Reducing Oral Pain and Dry Mouth After Surgery in Patients With Oropharyngeal Cancer

Study Overview
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Brief Summary
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This randomized pilot clinical trial studies dexamethasone in reducing oral pain and dry mouth after surgery in patients with oropharyngeal cancer. Dexamethasone may help lower pain and dry mouth caused by surgery.

Detailed Description
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PRIMARY OBJECTIVES: I. To prospectively determine if a longer 4-day course of dexamethasone (or equivalent) for the management of postoperative pain and dysphagia following transoral robotic surgery (TORS) is superior to the current standard of a single injection of dexamethasone 10 mg. SECONDARY OBJECTIVES: I. Determine the effect of postoperative corticosteroids on postoperative dysphagia following TORS. II. Determine the effect of postoperative corticosteroids on length of hospital stay following TORS. III. Determine the complications associated with postoperative corticosteroid use after TORS. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive dexamethasone intravenously (IV) at the time of surgery and orally (PO) every 8 hours for up to 4 days following surgery. ARM II: Patients receive dexamethasone IV at the time of surgery and placebo PO every 8 hours for up to 4 days following surgery. After completion of study treatment, patients are followed up for up to 12 months.

Official Title
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A Randomized, Placebo Controlled, Double Blinded Study of Corticosteroid Treatment for the Reduction of Postoperative Pain Following Transoral Robotic Surgery

Conditions
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Dysphagia, Pain, Stage I Oropharyngeal Squamous Cell Carcinoma, Stage II Oropharyngeal Squamous Cell Carcinoma, Stage III Oropharyngeal Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Dexamethasone
* Drug: Dexamethasone
* Other: Placebo
* Procedure: Quality-of-Life Assessment
* Other: Questionnaire Administration
* Procedure: Transoral Robotic Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be diagnosed with oropharyngeal squamous cell carcinoma (SCC) that are surgical candidates Macroscopic resection of the tumor via TORS must be planned with curative intent Patient must be willing to remain on corticosteroid therapy for 4 days postoperatively Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Patients with known distant metastases or other malignancies Patients with a history of allergy or adverse reaction to corticosteroids Patients with a history of diabetes Patients with fasting capillary blood glucose of > 140 on the day of surgery Patients on chronic corticosteroids Chronic alcohol abuse (> 6 alcoholic beverages daily) Patients with a history of severe chronic pain on high dose narcotics (> 25 mg of oxycodone or equivalent daily) preceding diagnosis of cancer Patients taking significant cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors or inducers, i.e. protease inhibitors (ritonavir, nelfinavir, etc), clarithromycin, ketoconazole, fluconazole, verapamil, diltiazem, carbamazepine, phenytoin, phenobarbital, Rifampin, efavirenz, nevirapine Patients who have received any investigational medication within 6 weeks of enrollment, or who are scheduled to receive an investigational drug during the course of the study Patients who will undergo complex head and neck surgery in addition to the TORS procedure requiring reconstruction with a free flap Patients who have had any previous head and neck surgery that has affected swallowing, voice or speech or who have had previous radiation to the head or neck Patients who have any confounding medical or neurological conditions that have the potential to affect cognition, speech or swallowing function; i.e. stroke, neurodegenerative disease, neuromuscular movement disorders, head injury, etcetera Psychiatric illness/social situations that would limit compliance with study requirements Excluded patients will be allowed to participate in the trial on an observational basis only

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (treatment)<br>Patients receive dexamethasone IV at the time of surgery and PO every 8 hours for up to 4 days following surgery. | Drug: Dexamethasone<br>* Given IV<br>* Other names: Visumetazone;Drug: Dexamethasone<br>* Given PO<br>* Other names: Visumetazone;Procedure: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>Procedure: Transoral Robotic Surgery<br>* Undergo TORS<br>* Other names: TORS;|
| Active Comparator: Arm II (control)<br>Patients receive dexamethasone IV at the time of surgery and placebo PO every 8 hours for up to 4 days following surgery. | Drug: Dexamethasone<br>* Given IV<br>* Other names: Visumetazone;Other: Placebo<br>* Given PO<br>* Other names: sham therapy;Procedure: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>Procedure: Transoral Robotic Surgery<br>* Undergo TORS<br>* Other names: TORS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Visual Analogue Scale (VAS) Score Measured at 10-point Scale | Visual Analog Scale (VAS) is a 0-10 scale for patients to indicate intensity level of pain with 0 indicating No pain and 10 indicating Worst possible, unbearable, excruciating pain. A descriptive time plot of VAS scores will be produced for all enrolled subjects, with loess curve fitted separately for the experimental and control groups. A linear mixed effects model will be used to compare the pain VAS scores between the experimental and control groups. | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complications Associated With Postoperative Corticosteroid Use After TORS | A descriptive statistical analysis will be conducted on complications. | Up to 30 days | 
| Eating Assessment Tool (EAT)-10 Scores | Statistical Analysis between placebo and steroid cohorts to assess differences. The Eating Assessment Tool (EAT-10) is a 10 item questionnaire that evaluates swallowing and the extent of how problematic with certain eating activities. Questions are answered using a five point (0-4) plus Not Applicable scale with 0 = No problem and 4= Severe problem. A descriptive time plot will be produced for EAT-10 scores using baseline and postoperative measurements on days 3 and day 7-21. Descriptive statistical analyses will be conducted for a summary of EAT-10 scores at baseline, days 3 and day 7-21 after surgery. A linear mixed effects model will be used to compare the EAT-10 scores between the two groups. | Up to 12 months | 
| Length of Hospital Stay (Number of Days Between the Date of Surgery and Date of Discharge) | Kaplan-Meier functions will be fitted to compare the length of hospital stay between the experimental and control groups. | Up to 21 days | 
| PSS Normalcy of Diet | Performance Status Score (PSS) - Normalcy of Diet score is a 0-100 scale that measures diet restrictions with 0= Non-oral feeding (tube fed) and 100 = Full diet (no restrictions) | 30 days | 
| Opioid Use |  | 3 days | 
| UM-QOL Eating | The University of Michigan Head and Neck Quality of Life Questionnaire (UM-QOL) is 20 item, 1-5 scale, questionnaire that measures how much the patient has been bothered during various activities as a result of head and neck condition or treatment in the past four weeks with 1= Not at all and 5=Extremely. The scores are calculated using a Likert Scale, which transforms the 1-5 choices into a 0-100 scale with 100 being normal and 0 being poor quality of life. This test contains separate domains (eating, etc.) that can be scored independently. Scores were analyzed between cohorts pre and post operatively. | 21 days | 
| Days With Feeding Tube |  | 12 months |