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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Pain, Head and Neck Squamous Cell Carcinoma, Stomatitis

Intervention / Treatment
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* Drug: Gabapentin
* Drug: Methadone Hydrochloride
* Drug: Oxycodone Hydrochloride
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (gabapentin)<br>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). | Drug: Gabapentin<br>* Given PO<br>* Other names: Neurontin;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Experimental: Arm II (gabapentin, methadone, oxycodone)<br>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). | Drug: Gabapentin<br>* Given PO<br>* Other names: Neurontin;Drug: Methadone Hydrochloride<br>* Given PO<br>* Other names: Methadose;Drug: Oxycodone Hydrochloride<br>* Given PO<br>* Other names: Roxicodone;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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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 |