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

A Randomized Phase III Trial of Gabapentin Versus Standard of Care for Prevention and Treatment of Mucositis in Locally Advanced Head and Neck Cancer Patients Undergoing Primary or Adjuvant Chemoradiation

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.

Study Overview

• Status: Completed
• Conditions: Mucositis; Malignant Head and Neck Neoplasm; Radiation-Induced Disorder
• Intervention / Treatment: Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Gabapentin; Other: Educational Intervention; Other: Pain Therapy; Drug: Oxycodone/Acetaminophen; Drug: Hydrocodone/Acetaminophen; Drug: Fentanyl; Drug: Ibuprofen; Drug: Magic Mouthwash

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.

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University/Ingram Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Other: Educational Intervention; Undergo oral care and pain management education session; Other Names: Education for Intervention; Other: Pain Therapy; Receive usual oral health care; Other Names: Analgesia; Pain Control; Pain Management; Pain; Drug: Oxycodone/Acetaminophen; Analgesia; Other Names: Percocet; Drug: Hydrocodone/Acetaminophen; Analgesia; Other Names: Vicodin; Lortab; Drug: Fentanyl; Transdermal Analgesia; Other Names: Duragesic; Drug: Ibuprofen; NSAID Analgesia; Other Names: Advil; Motrin; Drug: Magic Mouthwash; Oral Solution to treat mucositis; Other Names: Miracle Mouthwash; First-Mouthwash BLM; First-BXN Mouthwash
Experimental: 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.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Drug: Gabapentin; Given PO; Other Names: Gralise; Neurontin; 1-(aminomethyl) cyclohexaneacetic Acid, 60142-96-3,; Other: Educational Intervention; Undergo oral care and pain management education session; Other Names: Education for Intervention; Other: Pain Therapy; Receive usual oral health care; Other Names: Analgesia; Pain Control; Pain Management; Pain; Drug: Oxycodone/Acetaminophen; Analgesia; Other Names: Percocet; Drug: Hydrocodone/Acetaminophen; Analgesia; Other Names: Vicodin; Lortab; Drug: Fentanyl; Transdermal Analgesia; Other Names: Duragesic; Drug: Ibuprofen; NSAID Analgesia; Other Names: Advil; Motrin; Drug: Magic Mouthwash; Oral Solution to treat mucositis; Other Names: Miracle Mouthwash; First-Mouthwash BLM; First-BXN Mouthwash

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 3 months post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 3 months post-treatment
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.	Up to 3 months post-treatment

Collaborators and Investigators

• Sponsor: Vanderbilt-Ingram Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Derek Smith, DDS,PhD, Vanderbilt University/Ingram Cancer Center

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): September 1, 2019
• Study Completion (Actual): January 1, 2020

Study Registration Dates

• First Submitted: June 16, 2015
• First Submitted That Met QC Criteria: June 21, 2015
• First Posted (Estimate): June 24, 2015

Study Record Updates

• Last Update Posted (Actual): February 18, 2021
• Last Update Submitted That Met QC Criteria: January 28, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Diseases; Gastroenteritis; Stomatognathic Diseases; Mouth Diseases; Head and Neck Neoplasms; Mucositis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antipyretics; Analgesics, Opioid; Narcotics; Tranquilizing Agents; Psychotropic Drugs; Adjuvants, Anesthesia; Anti-Anxiety Agents; Anticonvulsants; Antimanic Agents; Respiratory System Agents; Antitussive Agents; Fentanyl; Gabapentin; Acetaminophen; Ibuprofen; Oxycodone; Hydrocodone; Acetaminophen, hydrocodone drug combination
• Other Study ID Numbers: VICC HN 1541 (Other Identifier: Vanderbilt University/Ingram Cancer Center); P30CA068485 (U.S. NIH Grant/Contract); NCI-2015-00750 (Registry Identifier: CTRP (Clinical Trial Reporting Program))