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

• Sponsor: Vanderbilt-Ingram Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02480114
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 79
• Location: 1
• Arms: 2
• Duration (Months): 54
• Patients Per Site Per Month: 1.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Malignant Head and Neck Neoplasm; Mucositis; Radiation-Induced Disorder	Other: Educational Intervention; Drug: Gabapentin; Other: Pain Therapy; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Oxycodone/Acetaminophen; Drug: Hydrocodone/Acetaminophen; Drug: Fentanyl; Drug: Ibuprofen; Drug: Magic Mouthwash	Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 79 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: 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
• Study Start Date: Jul 1, 2015
• Actual Primary Completion Date: Sep 1, 2019
• Actual Study Completion Date: Jan 1, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee	United States	37232

Sponsors and Collaborators

• Vanderbilt-Ingram Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Derek Smith, DDS,PhD, Vanderbilt University/Ingram Cancer Center

Study Documents (Full-Text)

• Informed Consent Form - Jan 23, 2019
• Study Protocol and Statistical Analysis Plan - Nov 28, 2017

More Information

Publications

None provided.

• Responsible Party: Derek Smith, Principal Investigator, Vanderbilt-Ingram Cancer Center
• ClinicalTrials.gov Identifier: NCT02480114
• Other Study ID Numbers: VICC HN 1541; NCI-2015-00750; VICC HN 1541; P30CA068485
• First Posted: Jun 24, 2015
• Last Update Posted: Feb 18, 2021
• Last Verified: Jan 1, 2021

• Additional relevant MeSH terms: Head and Neck Neoplasms; Mucositis; Acetaminophen; Ibuprofen; Acetaminophen, hydrocodone drug combination; Fentanyl; Oxycodone; Hydrocodone; Gabapentin

Study Results

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.

Arm/Group Title	Arm II Standard of Care Plus Gabapentin	Arm I Standard of Care
Arm/Group Description	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	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.
Period Title: Overall Study
STARTED	41	38
COMPLETED	32	30
NOT COMPLETED	9	8

Baseline Characteristics

Arm/Group Title	Arm I Standard of Care	Arm II Standard of Care Plus Gabapentin	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	38	41	79
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	32 84.2%	34 82.9%	66 83.5%
>=65 years	6 15.8%	7 17.1%	13 16.5%
Age (Years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Years]	61.5	61	61
Sex: Female, Male (Count of Participants)
Female	12 31.6%	14 34.1%	26 32.9%
Male	26 68.4%	27 65.9%	53 67.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 2.4%	1 1.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 7.9%	1 2.4%	4 5.1%
White	33 86.8%	39 95.1%	72 91.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 5.3%	0 0%	2 2.5%
Region of Enrollment (participants) [Number]
United States	38 100%	41 100%	79 100%

Outcome Measures

1. Primary Outcome

Title	Change in Pain Associated With Radiation-induced Mucositis, (Pain Subscale of the Vanderbilt Head and Neck Symptom Survey (VHNSS))
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Arm I Standard of Care	Arm II Standard of Care Plus Gabapentin
Arm/Group Description	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	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
Measure Participants	32	39
Median (Inter-Quartile Range) [score on a scale]	4.26	3.68

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I Standard of Care, Arm II Standard of Care Plus Gabapentin
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	Proportional Odds Regression
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.549
	Confidence Interval	(2-Sided) 95%; 0.364 to 0.827
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Participants With Grade 3 or 4 Adverse Events, (Graded Using Common Terminology Criteria for Adverse Events Criteria 4.0)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Arm I Standard of Care	Arm II Standard of Care Plus Gabapentin
Arm/Group Description	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	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
Measure Participants	32	39
Count of Participants [Participants]	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I Standard of Care, Arm II Standard of Care Plus Gabapentin
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Frequency and Severity of General Systemic Symptoms (Surveys Such as the Neurotoxicity Scale, Profile of Mood States, and Quality of Life Form)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Arm I Standard of Care	Arm II Standard of Care Plus Gabapentin
Arm/Group Description	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	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
Measure Participants	32	39
Median (Inter-Quartile Range) [score on a scale]	1.91	1.23

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I Standard of Care, Arm II Standard of Care Plus Gabapentin
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Proportional Odds Regression
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.371
	Confidence Interval	(2-Sided) 95%; 0.244 to 0.597
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Approximately 3 months after completion of treatment
Arm/Group Title	Arm I Standard of Care		Arm II Standard of Care Plus Gabapentin
Arm/Group Description	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		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
All Cause Mortality
	Arm I Standard of Care		Arm II Standard of Care Plus Gabapentin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/41 (0%)
Serious Adverse Events
	Arm I Standard of Care		Arm II Standard of Care Plus Gabapentin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/41 (0%)
Other (Not Including Serious) Adverse Events
	Arm I Standard of Care		Arm II Standard of Care Plus Gabapentin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		2/41 (4.9%)
General disorders
Fatigue	0/38 (0%)	0	2/41 (4.9%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.