Gabapentin for the Reduction of Radiation Therapy Induced Pain During the Treatment of Oropharyngeal Cancer

Randomized Phase III, Double-Blind, Placebo Controlled Study of Prophylactic Gabapentin for the Reduction of Radiation Therapy Induced Pain During the Treatment of Oropharyngeal Squamous Cell Carcinoma

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.

Study Overview

• Status: Completed
• Conditions: Oropharynx Cancer
• Intervention / Treatment: Drug: Placebo Oral Capsule; Drug: Gabapentin

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)

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control Arm; Standard supportive care during definitive treatment plus placebo	Drug: Placebo Oral Capsule; Placebo
Experimental: Experimental Arm; Gabapentin plus standard supportive care	Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Evaluated change in scores from baseline to 6 weeks post-treatment, approximately 13 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Administered at baseline and at 6-week follow-up endpoint, approximately 13 weeks
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	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).	Evaluated change in scores from baseline to 6 weeks post-treatment, approximately 13 weeks
Percent Weight Lost	Percent weight lost from baseline to week 7 of treatment (end of treatment)	Percent change from baseline to week 7 of treatment
Feeding Tube Placement	Measure of number of patients who required feeding tube placement at any time during the study period	Evaluated placement of feeding tube from baseline (start of radiation) to 6 weeks post-treatment, approximately 13 weeks

Collaborators and Investigators

• Sponsor: Henry Ford Health System
• Investigators: Study Chair: Farzan Siddiqui, MD PhD, Henry Ford Hospital

Publications and helpful links

General Publications

• Cook A, Modh A, Ali H, Sheqwara J, Chang S, Ghanem T, Momin S, Wu V, Tam S, Money S, Han X, Fakhoury L, Movsas B, Siddiqui F. Randomized Phase 3, Double-Blind, Placebo-Controlled Study of Prophylactic Gabapentin for the Reduction of Oral Mucositis Pain During the Treatment of Oropharyngeal Squamous Cell Carcinoma. Int J Radiat Oncol Biol Phys. 2022 Mar 15;112(4):926-937. doi: 10.1016/j.ijrobp.2021.11.012. Epub 2021 Nov 20.

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2017
• Primary Completion (Actual): December 9, 2020
• Study Completion (Actual): December 9, 2020

Study Registration Dates

• First Submitted: June 5, 2017
• First Submitted That Met QC Criteria: August 30, 2017
• First Posted (Actual): August 31, 2017

Study Record Updates

• Last Update Posted (Actual): January 26, 2022
• Last Update Submitted That Met QC Criteria: January 19, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Oropharyngeal Neoplasms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Anti-Anxiety Agents; Anticonvulsants; Antimanic Agents; Gabapentin
• Other Study ID Numbers: HFHS-Gabapentin/RT Study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No