Gabapentin Compared to Standard of Care in Preventing Mucositis in Patients With Stage III-IV Head and Neck Cancer Undergoing Primary or Adjuvant Chemoradiation Therapy

Phase 3

Completed

Conditions: Malignant Head and Neck Neoplasm
Mucositis
Radiation-Induced Disorder

Interventions: Other: Educational Intervention
Other: Pain Therapy
Drug: Gabapentin
Other: Quality-of-Life Assessment
Other: Questionnaire Administration
Drug: Oxycodone/Acetaminophen
Drug: Hydrocodone/Acetaminophen
Drug: Fentanyl
Drug: Ibuprofen
Drug: Magic Mouthwash

Registration Number: NCT02480114

Lead Sponsor: Vanderbilt-Ingram Cancer Center

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 79

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I Standard of Care	Educational Intervention	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.
Arm I Standard of Care	Pain Therapy	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.
Arm I Standard of Care	Quality-of-Life Assessment	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.
Arm I Standard of Care	Questionnaire Administration	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.
Arm I Standard of Care	Oxycodone/Acetaminophen	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.
Arm I Standard of Care	Hydrocodone/Acetaminophen	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.
Arm I Standard of Care	Ibuprofen	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.
Arm I Standard of Care	Magic Mouthwash	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.
Arm II Standard of Care Plus Gabapentin	Educational Intervention	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.
Arm II Standard of Care Plus Gabapentin	Pain Therapy	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.
Arm II Standard of Care Plus Gabapentin	Quality-of-Life Assessment	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.
Arm II Standard of Care Plus Gabapentin	Questionnaire Administration	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.
Arm II Standard of Care Plus Gabapentin	Oxycodone/Acetaminophen	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.
Arm II Standard of Care Plus Gabapentin	Hydrocodone/Acetaminophen	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.
Arm II Standard of Care Plus Gabapentin	Magic Mouthwash	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.
Arm I Standard of Care	Fentanyl	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.
Arm II Standard of Care Plus Gabapentin	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.
Arm II Standard of Care Plus Gabapentin	Fentanyl	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.
Arm II Standard of Care Plus Gabapentin	Ibuprofen	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.