Gabapentin, Methadone Hydrochloride, and Oxycodone Hydrochloride in Improving Quality of Life in Patients With Stage II-IV Head and Neck Cancer During Chemoradiation

Analysis of Analgesia Regimens During Concurrent Chemoradiation for Head and Neck Cancer: A Pilot Study

This randomized pilot clinical trial studies the side effects of gabapentin and how well it works when given together with methadone hydrochloride and oxycodone hydrochloride in improving quality of life in patients with stage II-IV head and neck cancer during chemoradiation. Gabapentin, methadone hydrochloride, and oxycodone hydrochloride may help relieve moderate or severe pain caused by head and neck cancer during and after chemoradiation therapy.

Study Overview

• Status: Completed
• Conditions: Pain; Stomatitis; Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Gabapentin; Drug: Methadone Hydrochloride; Drug: Oxycodone Hydrochloride

Detailed Description

PRIMARY OBJECTIVES:

I. Collect preliminary data on the safety and efficacy of two analgesic regimens that can be used to design larger studies for comparing such regimens.

SECONDARY OBJECTIVES:

I. Examine effects of the treatment regimens on pain control, oral mucositis, and quality-of-life ratings scores during and after chemoradiation therapy (CRT).

TERTIARY OBJECTIVES:

I. To assess treatment regimen effect on patient nutrition and hydration status during and after CRT (weight loss, vitals, oral [PO] tolerance, etc.).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive gabapentin PO thrice daily (TID) for up to 7 weeks during radiotherapy.

ARM II: Patients receive gabapentin PO TID, methadone hydrochloride PO twice daily (BID), and oxycodone hydrochloride PO every 8 hours (Q8H) as needed (PRN) for up to 7 weeks during radiotherapy.

All patients may continue to receive treatment for pain throughout their course of chemoradiation therapy (and up to 24 months following CRT if continuing on a pain regimen).

After completion of study, patients are followed up at 30 days, and at 3, 6, 9, and 12 months. Patients requiring prolonged analgesic therapy may be followed up every 6 months for 24 months.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who are eligible for chemoradiation therapy of the head and neck
• Baseline creatinine (Cr) no greater than 1.5 times the upper limit of normal
• Have a clinical stage II-IV head and neck carcinoma
• Have a pathologic diagnosis of squamous cell carcinoma of the head and neck region
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
• Ability to swallow and retain oral medication or take through a feeding tube
• Patients of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

• Patients who have previously been treated with surgery or radiation for head and neck cancer and/or are being treated for recurrent head and neck cancer
• Patients with known brain metastases will be excluded from this clinical trial
• Any patients prescribed medications for chronic pain and/or neuropathy will be excluded, including patients under treatment of a pain specialist or substance-abuse programs
• Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant or nursing female patients
• Unwilling or unable to follow protocol requirements
• Any condition which in the Investigator's opinion deems the patient an unsuitable candidate to receive study drug
• Received an investigational agent within 30 days prior to enrollment
• Patients on medications that prolong QT interval
• Patients on dialysis or with transplanted organs
• Patients already enrolled on other studies of systemic pain control agents

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
Experimental: Arm I (gabapentin); Patients receive gabapentin PO TID for up to 7 weeks during radiotherapy. All patients may continue to receive treatment for pain throughout their course of chemoradiation therapy (and up to 24 months following CRT if continuing on a pain regimen).	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
Experimental: Arm II (gabapentin, methadone, oxycodone); Patients receive gabapentin PO TID, methadone hydrochloride PO BID, and oxycodone hydrochloride PO Q8H PRN for up to 7 weeks during radiotherapy. All patients may continue to receive treatment for pain throughout their course of chemoradiation therapy (and up to 24 months following CRT if continuing on a pain regimen).	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; Drug: Methadone Hydrochloride; Given PO; Other Names: Dolophine; Methadose; Adanon; Althose; Drug: Oxycodone Hydrochloride; Given PO; Other Names: Oxecta; OxyContin; Roxicodone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pain levels via Oral Mucositis Daily Questionnaire (OMDQ), European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30, Head and Neck Quality of Life Survey, and physical evaluations	Evaluated using a repeated measures model. Tested using a two-sided 0.05 significance level. Post hoc analyses will be done with multiple comparisons adjusted for using the Bonferroni method. Assumptions of normality and equal variance will be examined, and transformations will be used as appropriate.	Baseline to up to 24 months
Incidence of side effects or drug intolerance	Will be graded and recorded. Tested using a two-sided 0.05 significance level. Post hoc analyses will be done with multiple comparisons adjusted for using the Bonferroni method. Assumptions of normality and equal variance will be examined, and transformations will be used as appropriate. The frequency of toxicities will be tabulated by grade by treatment arm.	Up to 24 months
Proportion of patients who require higher equivalents of narcotic support added to their analgesia regimen in each arm	Each patient requiring rescue medication for breakthrough or refractory pain will be counted as a failure for that specific regimen. At the end of the trial, number of failures will be compared between the two treatment arms using Fisher's exact test. Total amount of opioid intake mean will be compared using a t-test between the two arms. Tested using a two-sided 0.05 significance level. Post hoc analyses will be done with multiple comparisons adjusted for using the Bonferroni method. Assumptions of normality and equal variance will be examined, and transformations will be used as appropriate	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in oral mucositis rating scores during and after CRT, using the OMDQ	The total score of the OMDQ questionnaire will be recorded after each follow-up visit. Tested using a two-sided 0.05 significance level. Post hoc analyses will be done with multiple comparisons adjusted for using the Bonferroni method. Assumptions of normality and equal variance will be examined, and transformations will be used as appropriate.	Baseline to up to 24 months
Change in quality of life rating scores during and after CRT, using the EORTC QLQ-C30 and H&N35	The total score of the EORTC questionnaires will be recorded after each follow-up visit. Tested using a two-sided 0.05 significance level. Post hoc analyses will be done with multiple comparisons adjusted for using the Bonferroni method. Assumptions of normality and equal variance will be examined, and transformations will be used as appropriate.	Baseline to up to 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in patient hydration and nutrition using the OMDQ	Tested using a two-sided 0.05 significance level. Post hoc analyses will be done with multiple comparisons adjusted for using the Bonferroni method. Assumptions of normality and equal variance will be examined, and transformations will be used as appropriate.	Baseline to up to 24 months

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start: April 24, 2015
• Primary Completion (Actual): June 14, 2018
• Study Completion (Actual): June 14, 2018

Study Registration Dates

• First Submitted: August 19, 2015
• First Submitted That Met QC Criteria: August 24, 2015
• First Posted (Estimate): August 25, 2015

Study Record Updates

• Last Update Posted (Actual): July 25, 2022
• Last Update Submitted That Met QC Criteria: July 20, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Stomatognathic Diseases; Mouth Diseases; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck; Stomatitis; 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; Analgesics, Opioid; Narcotics; Tranquilizing Agents; Psychotropic Drugs; Anti-Anxiety Agents; Anticonvulsants; Antimanic Agents; Respiratory System Agents; Antitussive Agents; Gabapentin; Oxycodone; Methadone
• Other Study ID Numbers: I 262314 (Other Identifier: Roswell Park Cancer Institute); NCI-2015-01338 (Registry Identifier: CTRP (Clinical Trial Reporting Program))