Malignant Head and Neck Neoplasm, Mucositis, Radiation-Induced Disorder
Conditions
Brief summary
This randomized phase III trial studies how well gabapentin plus standard of care work compares to standard of care without Gabapentin in preventing inflammation of the mucous membranes (mucositis) in patients with stage III-IV head and neck cancer that are undergoing primary or subsequent (adjuvant) chemoradiation therapy. Radiation therapy to the head and neck may cause a burn involving the inside of the mouth, throat, and nasal passages, resulting in pain. Gabapentin may help prevent (or minimize) pain associated with radiation-induced mucositis in patients with head and neck cancer.
Detailed description
Primary Objectives: \- To determine whether gabapentin used as a preventive measure during chemoradiation can reduce radiation-induced mucositis associated pain in head and neck cancer patients as measured by: 1) pain scores on the Vanderbilt Head and Neck Symptom Survey (VHNSS version 2.), and 2) analgesic use. Secondary Objectives: * To assess the safety (grade 3 or 4 adverse events) and tolerability of using gabapentin (discontinuation of drug due to side effects - yes or no) * To correlate pain severity with frequency and severity of general systemic symptoms. Exploratory Objectives: \- To determine whether pain control is associated with weight loss (in pounds) and duration of use of percutaneous endoscopic gastrostomy utilization (in days). OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Standard of Care (usual care) - Patients receive consisting of oral health measures, oral rinsing, miracle mouthwash, nonsteroidal anti-inflammatories, and opioid analgesics. Patients also undergo an education session at the beginning of chemoradiation treatment to review foundations of oral care and pain management. ARM II: Standard of Care plus Gabapentin - Patients receive standard of care and undergo an education session as in Arm I. Patients also receive gabapentin orally (PO) three times a day throughout chemoradiation treatment (approximately 5-7 weeks) and until mucositis resolves and pain subsides. After completion of study treatment, patients are followed up monthly for 3 months.
Interventions
OTHEREducational Intervention
Undergo oral care and pain management education session
DRUGGabapentin
Given PO
OTHERPain Therapy
Receive usual oral health care
OTHERQuality-of-Life Assessment
Ancillary studies
OTHERQuestionnaire Administration
Ancillary studies
Analgesia
Analgesia
DRUGFentanyl
Transdermal Analgesia
DRUGIbuprofen
NSAID Analgesia
DRUGMagic Mouthwash
Oral Solution to treat mucositis
Sponsors
National Cancer Institute (NCI)
Vanderbilt-Ingram Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically proven cancer of the head and neck cancer * Stage 3 or 4 * Planned primary or adjuvant chemoradiation therapy * Willing and able to provide informed consent * English speaking
Exclusion criteria
* Currently on gabapentin * Prior non-tolerance of gabapentin * History of seizure disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pain Associated With Radiation-induced Mucositis, (Pain Subscale of the Vanderbilt Head and Neck Symptom Survey (VHNSS)) | Up to 3 months post-treatment | The pain subscale is composed of 4 items of the Vanderbilt Head and Neck Symptom Survey. The subscale score was calculated by taking the first non-negative principle component of the 4 items. The scale was scores range from 0 to 10 with 10 representing the worst pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Grade 3 or 4 Adverse Events, (Graded Using Common Terminology Criteria for Adverse Events Criteria 4.0) | Up to 3 months post-treatment | Graphical and descriptive statistical summaries will be generated. Mixed-level general linear modeling will be used. All tests of statistical significance will maintain maximum Type I error of 0.05 (p \< 0.05). Frequency distributions will summarize the safety outcome. |
| Frequency and Severity of General Systemic Symptoms (Surveys Such as the Neurotoxicity Scale, Profile of Mood States, and Quality of Life Form) | Up to 3 months post-treatment | Pain severity will be correlated with frequency and severity of general systemic symptoms. Graphical and descriptive statistical summaries will be generated. Mixed-level general linear modeling will be used. All tests of statistical significance will maintain maximum Type I error of 0.05 (p \< 0.05). Baseline pain scores will be included as a covariate in the analyses of the outcome. The General Symptom Survey is a ten item patient reported outcome measure and outcomes were averaged as there is only one item per symptom category. 0 represented no presence of the symptom with a score of 10 representing the most severe symptom. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at Vanderbilt Medical Center in Nashville, TN from July 2015 to May 2019. 79 participants were recruited and 8 of those withdrew.
Participants by arm
| Arm | Count |
|---|---|
| Arm I Standard of Care Patients receive standard of care consisting of oral health measures, oral rinsing, miracle mouthwash, nonsteroidal anti-inflammatories, and opioid analgesics. Patients also undergo an education session at the beginning of treatment to review foundations of oral care and pain management.
Educational Intervention: Undergo oral care and pain management education session
Pain Therapy: Receive usual oral health care
Quality-of-Life Assessment: Ancillary studies
Questionnaire Administration: Ancillary studies
Oxycodone/Acetaminophen: Analgesia
Hydrocodone/Acetaminophen: Analgesia
Fentanyl: Transdermal Analgesia
Ibuprofen: NSAID Analgesia
Magic Mouthwash: Oral Solution to treat mucositis | 38 |
| Arm II Standard of Care Plus Gabapentin Patients receive standard of care and undergo an education session as in Arm I. Patients also receive gabapentin PO three times a day throughout chemoradiation treatment (approximately 5-7 weeks) and until mucositis resolves and pain subsides.
Educational Intervention: Undergo oral care and pain management education session
Gabapentin: Given PO
Pain Therapy: Receive usual oral health care
Quality-of-Life Assessment: Ancillary studies
Questionnaire Administration: Ancillary studies
Oxycodone/Acetaminophen: Analgesia
Hydrocodone/Acetaminophen: Analgesia
Fentanyl: Transdermal Analgesia
Ibuprofen: NSAID Analgesia
Magic Mouthwash: Oral Solution to treat mucositis | 41 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Disease progression | 3 | 0 |
| Overall Study | Improper completion of survey | 1 | 1 |
| Overall Study | Not completing surveys | 3 | 2 |
| Overall Study | Not eligible | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 4 |
Baseline characteristics
| Characteristic | Arm II Standard of Care Plus Gabapentin | Total | Arm I Standard of Care |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 13 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 34 Participants | 66 Participants | 32 Participants |
| Age, Continuous | 61 Years | 61 Years | 61.5 Years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 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 | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 39 Participants | 72 Participants | 33 Participants |
| Region of Enrollment United States | 41 participants | 79 participants | 38 participants |
| Sex: Female, Male Female | 14 Participants | 26 Participants | 12 Participants |
| Sex: Female, Male Male | 27 Participants | 53 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 0 / 41 |
| other Total, other adverse events | 0 / 38 | 2 / 41 |
| serious Total, serious adverse events | 0 / 38 | 0 / 41 |
Outcome results
Primary
Change in Pain Associated With Radiation-induced Mucositis, (Pain Subscale of the Vanderbilt Head and Neck Symptom Survey (VHNSS))
The pain subscale is composed of 4 items of the Vanderbilt Head and Neck Symptom Survey. The subscale score was calculated by taking the first non-negative principle component of the 4 items. The scale was scores range from 0 to 10 with 10 representing the worst pain.
Time frame: Up to 3 months post-treatment
Population: Longitudinal analysis was completed including all patients in both arms of the study. Although some patients stopped filling out surveys part way through the study and therefore are not marked as 'complete' in the patient flow section, the data they did provide was still used for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I Standard of Care | Change in Pain Associated With Radiation-induced Mucositis, (Pain Subscale of the Vanderbilt Head and Neck Symptom Survey (VHNSS)) | 4.26 score on a scale |
| Arm II Standard of Care Plus Gabapentin | Change in Pain Associated With Radiation-induced Mucositis, (Pain Subscale of the Vanderbilt Head and Neck Symptom Survey (VHNSS)) | 3.68 score on a scale |
p-value: 0.00495% CI: [0.364, 0.827]Proportional Odds Regression
Secondary
Frequency and Severity of General Systemic Symptoms (Surveys Such as the Neurotoxicity Scale, Profile of Mood States, and Quality of Life Form)
Pain severity will be correlated with frequency and severity of general systemic symptoms. Graphical and descriptive statistical summaries will be generated. Mixed-level general linear modeling will be used. All tests of statistical significance will maintain maximum Type I error of 0.05 (p \< 0.05). Baseline pain scores will be included as a covariate in the analyses of the outcome. The General Symptom Survey is a ten item patient reported outcome measure and outcomes were averaged as there is only one item per symptom category. 0 represented no presence of the symptom with a score of 10 representing the most severe symptom.
Time frame: Up to 3 months post-treatment
Population: Although some patients stopped filling out surveys part way through the study and therefore are not marked as 'complete' in the patient flow section, the data they did provide was still used for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I Standard of Care | Frequency and Severity of General Systemic Symptoms (Surveys Such as the Neurotoxicity Scale, Profile of Mood States, and Quality of Life Form) | 1.91 score on a scale |
| Arm II Standard of Care Plus Gabapentin | Frequency and Severity of General Systemic Symptoms (Surveys Such as the Neurotoxicity Scale, Profile of Mood States, and Quality of Life Form) | 1.23 score on a scale |
p-value: <0.00195% CI: [0.244, 0.597]Proportional Odds Regression
Secondary
Number of Participants With Grade 3 or 4 Adverse Events, (Graded Using Common Terminology Criteria for Adverse Events Criteria 4.0)
Graphical and descriptive statistical summaries will be generated. Mixed-level general linear modeling will be used. All tests of statistical significance will maintain maximum Type I error of 0.05 (p \< 0.05). Frequency distributions will summarize the safety outcome.
Time frame: Up to 3 months post-treatment
Population: All patients in both arms were analyzed. Although some patients stopped filling out surveys part way through the study and therefore are not marked as 'complete' in the patient flow section, the data they did provide was still used for analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I Standard of Care | Number of Participants With Grade 3 or 4 Adverse Events, (Graded Using Common Terminology Criteria for Adverse Events Criteria 4.0) | 0 Participants |
| Arm II Standard of Care Plus Gabapentin | Number of Participants With Grade 3 or 4 Adverse Events, (Graded Using Common Terminology Criteria for Adverse Events Criteria 4.0) | 0 Participants |
p-value: 1Fisher Exact