Oropharynx Cancer
Conditions
Brief summary
Strategies to minimize and mitigate external beam radiation therapy related mucositis and pain during the treatment of head and neck cancer remain limited. The investigators hypothesize that gabapentin could be used to delay or reduce treatment-related pain, reliance on opioid medication, and improve the quality of life for these patients.
Detailed description
The specific aims of this proposed study include the following: * Evaluate the reduction or delay of mucositis related pain and morbidity with the use of gabapentin in patients with stage III or IV oropharyngeal squamous cell carcinoma undergoing definitive radiation with concurrent chemotherapy as part of their cancer management, compared to standard supportive side effect mitigation - using patient reported quality of life endpoints such as the Patient-Reported Oral Mucositis Symptoms (PROMS) scale. * Assess morphine-equivalent opioid use in both treatment arms by collecting the patient's narcotic use in the previous 24-hour period at each weekly evaluation during radiation treatment. * Report on change in Speech and swallow performance, as measured by the Performance Status Scale (PSS) for Head and Neck Cancer Patients * Evaluate changes in weight from baseline throughout treatment between the two arms. * Assess feeding tube requirements during treatment. * Evaluate the adverse events associated with gabapentin. * Evaluate the severity of radiation mucositis (grade 3-4, CTCAE, v. 4)
Interventions
DRUGGabapentin
Gabapentin is an anticonvulsant and has been used to manage neuropathic pain and is FDA-approved for the treatment of post-herpetic neuralgia and partial onset seizures
DRUGPlacebo Oral Capsule
Placebo
Sponsors
Henry Ford Health System
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Patients being treated with combination chemotherapy and radiation therapy daily for locally advanced (stage III-IV) squamous cell carcinoma of the oropharynx. * Age ≥ 18. * ECOG performance status ≤ 1. * Patients must provide study specific informed consent prior to study entry and be able to fill out toxicity and quality of life related questionnaires.
Exclusion criteria
* Patients may not be receiving gabapentin, any other investigational agents, or other anticonvulsants. * Patients with metastatic disease are excluded from this clinical trial. * Patient with allergies or hypersensitivity to gabapentin. * Patients receiving surgery as part of their definitive management. * Patients who have received prior chemotherapy or radiation therapy. * Patients unable to complete the required forms; however, verbal completion is adequate if recorded on the form daily. * Uncontrolled serious illness including, but not limited to, ongoing or serious active infection requiring IV antibiotics for over 30 days, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia other than chronic, stable atrial fibrillation, or psychiatric illness/social situations that would limit compliance with study requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Quality of Life From Mucositis-related Pain Measured by the Patient-Reported Oral Mucositis Symptoms (PROMS) Scale From Baseline to Follow-up | Evaluated change in scores from baseline to 6 weeks post-treatment, approximately 13 weeks | Scale tile: Patient Reported Oral Mucositis Symptoms scale, range 0-1000, higher scores indicate worse outcomes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Total FACT-HN Scores From Baseline to Follow-up | Administered at baseline and at 6-week follow-up endpoint, approximately 13 weeks | Scale: Functional Assessment of Cancer Therapy-Trial Outcome (FACT-HN), range 0-148, higher scores indicate better outcomes |
| Average Opioid Use, Measured in Morphine Equivalents Per Day. | Over the entire study period from baseline to follow-up, approximately 13 weeks | — |
| Change in PRO-CTCAE Scores From Baseline to Follow-up | Evaluated change in scores from baseline to 6 weeks post-treatment, approximately 13 weeks | Scale: Patient-reported outcomes of Common Terminology Criteria for Adverse Events (PRO-CTCAE), 5-point Likert scale, higher scores indicate worse outcomes. Range of scores 0-40 (min-max). |
| Percent Weight Lost | Percent change from baseline to week 7 of treatment | Percent weight lost from baseline to week 7 of treatment (end of treatment) |
| Feeding Tube Placement | Evaluated placement of feeding tube from baseline (start of radiation) to 6 weeks post-treatment, approximately 13 weeks | Measure of number of patients who required feeding tube placement at any time during the study period |
Countries
United States
Participant flow
Pre-assignment details
After 65 patients were enrolled, 7 more were excluded from analysis, leaving 58 patients analyzed. These patients were excluded because they received immunotherapy (n=1), pursued treatment elsewhere (n=2), developed acute kidney injury (n=1), and refused to take medication during the first two weeks of treatment (n=3).
Participants by arm
| Arm | Count |
|---|---|
| Control Arm Standard supportive care during definitive treatment plus placebo
Placebo Oral Capsule: Placebo | 29 |
| Experimental Arm Gabapentin plus standard supportive care
Gabapentin: Gabapentin is an anticonvulsant and has been used to manage neuropathic pain and is FDA-approved for the treatment of post-herpetic neuralgia and partial onset seizures | 29 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 4 | 3 |
Baseline characteristics
| Characteristic | Experimental Arm | Total | Control Arm |
|---|---|---|---|
| Age, Continuous | 60.2 years STANDARD_DEVIATION 10.4 | 59.8 years STANDARD_DEVIATION 9.5 | 59.4 years STANDARD_DEVIATION 8.5 |
| Clinical N Stage 0 | 2 Participants | 2 Participants | 0 Participants |
| Clinical N Stage 1 | 15 Participants | 32 Participants | 17 Participants |
| Clinical N Stage 2 | 6 Participants | 13 Participants | 7 Participants |
| Clinical N Stage 2a | 1 Participants | 1 Participants | 0 Participants |
| Clinical N Stage 2b | 1 Participants | 4 Participants | 3 Participants |
| Clinical N Stage 2c | 1 Participants | 3 Participants | 2 Participants |
| Clinical N Stage 3 | 3 Participants | 3 Participants | 0 Participants |
| Clinical T Stage 1 | 6 Participants | 14 Participants | 8 Participants |
| Clinical T Stage 2 | 10 Participants | 21 Participants | 11 Participants |
| Clinical T Stage 3 | 7 Participants | 12 Participants | 5 Participants |
| Clinical T Stage 4 | 4 Participants | 6 Participants | 2 Participants |
| Clinical T Stage 4a | 1 Participants | 2 Participants | 1 Participants |
| Clinical T Stage 4b | 0 Participants | 1 Participants | 1 Participants |
| Clinical T Stage Tx or T0 | 1 Participants | 2 Participants | 1 Participants |
| Gross Tumor Volume of Primary Tumor | 21.5 cubic centimeter (cc) STANDARD_DEVIATION 18.5 | 21.8 cubic centimeter (cc) STANDARD_DEVIATION 17.9 | 22.0 cubic centimeter (cc) STANDARD_DEVIATION 17.2 |
| Gross Tumor Volume Total (cc) | 49.2 cc STANDARD_DEVIATION 31.5 | 49.8 cc STANDARD_DEVIATION 36.2 | 50.3 cc STANDARD_DEVIATION 40.8 |
| HPV Status Negative | 3 Participants | 8 Participants | 5 Participants |
| HPV Status Positive | 26 Participants | 49 Participants | 23 Participants |
| HPV Status Unknown | 0 Participants | 1 Participants | 1 Participants |
| Opioid Use at Baseline | 4 Participants | 7 Participants | 3 Participants |
| Primary Site Oropharynx-base of tongue | 11 Participants | 21 Participants | 10 Participants |
| Primary Site Oropharynx-not specified | 1 Participants | 4 Participants | 3 Participants |
| Primary Site Oropharynx-soft palate | 0 Participants | 1 Participants | 1 Participants |
| Primary Site Oropharynx-tonsil | 17 Participants | 29 Participants | 12 Participants |
| Primary Site Oropharynx-vallecula | 0 Participants | 2 Participants | 2 Participants |
| Primary Site Unknown primary | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 25 Participants | 50 Participants | 25 Participants |
| Sex: Female, Male Female | 5 Participants | 9 Participants | 4 Participants |
| Sex: Female, Male Male | 24 Participants | 49 Participants | 25 Participants |
| Smoking Status | 9 Participants | 16 Participants | 7 Participants |
| Type of Chemotherapy Carboplatin-based | 4 Participants | 7 Participants | 3 Participants |
| Type of Chemotherapy Cisplatin every 3 weeks | 16 Participants | 32 Participants | 16 Participants |
| Type of Chemotherapy Cisplatin weekly | 9 Participants | 19 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 29 |
| other Total, other adverse events | 0 / 29 | 0 / 29 |
| serious Total, serious adverse events | 0 / 29 | 0 / 29 |
Outcome results
Primary
Change in Quality of Life From Mucositis-related Pain Measured by the Patient-Reported Oral Mucositis Symptoms (PROMS) Scale From Baseline to Follow-up
Scale tile: Patient Reported Oral Mucositis Symptoms scale, range 0-1000, higher scores indicate worse outcomes
Time frame: Evaluated change in scores from baseline to 6 weeks post-treatment, approximately 13 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Arm | Change in Quality of Life From Mucositis-related Pain Measured by the Patient-Reported Oral Mucositis Symptoms (PROMS) Scale From Baseline to Follow-up | 20.1 score on a scale | Standard Deviation 16.8 |
| Experimental Arm | Change in Quality of Life From Mucositis-related Pain Measured by the Patient-Reported Oral Mucositis Symptoms (PROMS) Scale From Baseline to Follow-up | 29.1 score on a scale | Standard Deviation 22.5 |
p-value: 0.11ANOVA
Secondary
Average Opioid Use, Measured in Morphine Equivalents Per Day.
Time frame: Over the entire study period from baseline to follow-up, approximately 13 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Control Arm | Average Opioid Use, Measured in Morphine Equivalents Per Day. | 15.6 Daily morphine equivalents |
| Experimental Arm | Average Opioid Use, Measured in Morphine Equivalents Per Day. | 22.2 Daily morphine equivalents |
p-value: 0.32Wilcoxon (Mann-Whitney)
Secondary
Change in PRO-CTCAE Scores From Baseline to Follow-up
Scale: Patient-reported outcomes of Common Terminology Criteria for Adverse Events (PRO-CTCAE), 5-point Likert scale, higher scores indicate worse outcomes. Range of scores 0-40 (min-max).
Time frame: Evaluated change in scores from baseline to 6 weeks post-treatment, approximately 13 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Control Arm | Change in PRO-CTCAE Scores From Baseline to Follow-up | 1.0 units on a scale |
| Experimental Arm | Change in PRO-CTCAE Scores From Baseline to Follow-up | 6.5 units on a scale |
p-value: <0.01Wilcoxon (Mann-Whitney)
Secondary
Change in Total FACT-HN Scores From Baseline to Follow-up
Scale: Functional Assessment of Cancer Therapy-Trial Outcome (FACT-HN), range 0-148, higher scores indicate better outcomes
Time frame: Administered at baseline and at 6-week follow-up endpoint, approximately 13 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Control Arm | Change in Total FACT-HN Scores From Baseline to Follow-up | -15.0 units on a scale |
| Experimental Arm | Change in Total FACT-HN Scores From Baseline to Follow-up | -20.0 units on a scale |
p-value: 0.08Wilcoxon (Mann-Whitney)
Secondary
Feeding Tube Placement
Measure of number of patients who required feeding tube placement at any time during the study period
Time frame: Evaluated placement of feeding tube from baseline (start of radiation) to 6 weeks post-treatment, approximately 13 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control Arm | Feeding Tube Placement | 6 Participants |
| Experimental Arm | Feeding Tube Placement | 18 Participants |
p-value: <0.01Chi-squared
Secondary
Percent Weight Lost
Percent weight lost from baseline to week 7 of treatment (end of treatment)
Time frame: Percent change from baseline to week 7 of treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Control Arm | Percent Weight Lost | -10.7 Percent change |
| Experimental Arm | Percent Weight Lost | -11.4 Percent change |
p-value: 0.81Wilcoxon (Mann-Whitney)