Dysphagia, Pain, Stage I Oropharyngeal Squamous Cell Carcinoma, Stage II Oropharyngeal Squamous Cell Carcinoma, Stage III Oropharyngeal Squamous Cell Carcinoma
Conditions
Brief summary
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
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.
Interventions
DRUGDexamethasone
Given IV
OTHERPlacebo
Given PO
PROCEDUREQuality-of-Life Assessment
Ancillary studies
OTHERQuestionnaire Administration
Ancillary studies
PROCEDURETransoral Robotic Surgery
Undergo TORS
Sponsors
National Cancer Institute (NCI)
OHSU Knight Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Visual Analogue Scale (VAS) Score Measured at 10-point Scale | 21 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Eating Assessment Tool (EAT)-10 Scores | Up to 12 months | 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. |
| Length of Hospital Stay (Number of Days Between the Date of Surgery and Date of Discharge) | Up to 21 days | Kaplan-Meier functions will be fitted to compare the length of hospital stay between the experimental and control groups. |
| PSS Normalcy of Diet | 30 days | 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) |
| Complications Associated With Postoperative Corticosteroid Use After TORS | Up to 30 days | A descriptive statistical analysis will be conducted on complications. |
| UM-QOL Eating | 21 days | 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. |
| Days With Feeding Tube | 12 months | — |
| Opioid Use | 3 days | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Treatment) Patients receive dexamethasone IV at the time of surgery and PO every 8 hours for up to 4 days following surgery.
Dexamethasone: Given IV
Dexamethasone: Given PO
Quality-of-Life Assessment: Ancillary studies
Questionnaire Administration: Ancillary studies
Transoral Robotic Surgery: Undergo TORS | 35 |
| Arm II (Control) Patients receive dexamethasone IV at the time of surgery and placebo PO every 8 hours for up to 4 days following surgery.
Dexamethasone: Given IV
Placebo: Given PO
Quality-of-Life Assessment: Ancillary studies
Questionnaire Administration: Ancillary studies
Transoral Robotic Surgery: Undergo TORS | 33 |
| Total | 68 |
Baseline characteristics
| Characteristic | Arm II (Control) | Arm I (Treatment) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 3 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants | 32 Participants | 60 Participants |
| Age, Continuous | 60 years | 56 years | 58 years |
| EAT-10 score | 3.5 units on a scale STANDARD_DEVIATION 6.2 | 5.9 units on a scale STANDARD_DEVIATION 7.6 | 4.6 units on a scale STANDARD_DEVIATION 6.9 |
| PSS normalcy of diet | 94.2 units on a scale STANDARD_DEVIATION 15 | 92.3 units on a scale STANDARD_DEVIATION 16.4 | 93.8 units on a scale STANDARD_DEVIATION 15.4 |
| Region of Enrollment United States | 33 participants | 35 participants | 68 participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 29 Participants | 32 Participants | 61 Participants |
| Tumor stage T1 | 15 Participants | 21 Participants | 36 Participants |
| Tumor stage T2 | 18 Participants | 14 Participants | 32 Participants |
| UM-QOL eating score | 93.75 units on a scale STANDARD_DEVIATION 12.7 | 89.6 units on a scale STANDARD_DEVIATION 17.8 | 89.6 units on a scale STANDARD_DEVIATION 17.8 |
| VAS pain score | 0.6 units on a scale STANDARD_DEVIATION 1.3 | 1.1 units on a scale STANDARD_DEVIATION 1.8 | 0.9 units on a scale STANDARD_DEVIATION 1.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 35 | 0 / 33 |
| serious Total, serious adverse events | 10 / 35 | 7 / 33 |
Outcome results
Primary
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.
Time frame: 21 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm I (Treatment) | Pain Visual Analogue Scale (VAS) Score Measured at 10-point Scale | Postoperative day #3 | 5.3 units on a scale | Standard Deviation 2 |
| Arm I (Treatment) | Pain Visual Analogue Scale (VAS) Score Measured at 10-point Scale | Postoperative day #1 | 7.4 units on a scale | Standard Deviation 2 |
| Arm I (Treatment) | Pain Visual Analogue Scale (VAS) Score Measured at 10-point Scale | Postoperative day #7-21 | 3.0 units on a scale | Standard Deviation 1.8 |
| Arm I (Treatment) | Pain Visual Analogue Scale (VAS) Score Measured at 10-point Scale | Postoperative day #2 | 6.0 units on a scale | Standard Deviation 2 |
| Arm II (Control) | Pain Visual Analogue Scale (VAS) Score Measured at 10-point Scale | Postoperative day #7-21 | 2.5 units on a scale | Standard Deviation 1.9 |
| Arm II (Control) | Pain Visual Analogue Scale (VAS) Score Measured at 10-point Scale | Postoperative day #1 | 6.8 units on a scale | Standard Deviation 2.3 |
| Arm II (Control) | Pain Visual Analogue Scale (VAS) Score Measured at 10-point Scale | Postoperative day #3 | 6.7 units on a scale | Standard Deviation 1.9 |
| Arm II (Control) | Pain Visual Analogue Scale (VAS) Score Measured at 10-point Scale | Postoperative day #2 | 6.4 units on a scale | Standard Deviation 2.1 |
p-value: 0.25Mixed Models Analysis
Secondary
Complications Associated With Postoperative Corticosteroid Use After TORS
A descriptive statistical analysis will be conducted on complications.
Time frame: Up to 30 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm I (Treatment) | Complications Associated With Postoperative Corticosteroid Use After TORS | complication present | 10 Participants |
| Arm I (Treatment) | Complications Associated With Postoperative Corticosteroid Use After TORS | no complication | 25 Participants |
| Arm II (Control) | Complications Associated With Postoperative Corticosteroid Use After TORS | complication present | 7 Participants |
| Arm II (Control) | Complications Associated With Postoperative Corticosteroid Use After TORS | no complication | 26 Participants |
Secondary
Days With Feeding Tube
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Treatment) | Days With Feeding Tube | 4 days |
| Arm II (Control) | Days With Feeding Tube | 11 days |
p-value: 0.15Log Rank
Secondary
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.
Time frame: Up to 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Treatment) | Eating Assessment Tool (EAT)-10 Scores | 20.0 units on a scale | Standard Deviation 8.3 |
| Arm II (Control) | Eating Assessment Tool (EAT)-10 Scores | 20.2 units on a scale | Standard Deviation 10.7 |
Secondary
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.
Time frame: Up to 21 days
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Arm I (Treatment) | Length of Hospital Stay (Number of Days Between the Date of Surgery and Date of Discharge) | 5 days | Standard Deviation 1.9 |
| Arm II (Control) | Length of Hospital Stay (Number of Days Between the Date of Surgery and Date of Discharge) | 4 days | Standard Deviation 1.2 |
p-value: <0.001Log Rank
Secondary
Opioid Use
Time frame: 3 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Treatment) | Opioid Use | 137.1 mg of oxycodone equivalent | Standard Deviation 115.2 |
| Arm II (Control) | Opioid Use | 147.3 mg of oxycodone equivalent | Standard Deviation 90.4 |
p-value: 0.33Wilcoxon (Mann-Whitney)
Secondary
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)
Time frame: 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Treatment) | PSS Normalcy of Diet | 51.7 units on a scale | Standard Deviation 24.4 |
| Arm II (Control) | PSS Normalcy of Diet | 36.7 units on a scale | Standard Deviation 23.4 |
p-value: 0.009Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: 21 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Treatment) | UM-QOL Eating | 59.3 units on a scale | Standard Deviation 19.5 |
| Arm II (Control) | UM-QOL Eating | 60.1 units on a scale | Standard Deviation 19.4 |
p-value: 0.96Wilcoxon (Mann-Whitney)