Gabapentin, Methadone, and Oxycodone With or Without Venlafaxine Hydrochloride in Managing Pain in Participants With Stage II-IV Squamous Cell Head and Neck Cancer Undergoing Chemoradiation Therapy

April 13, 2026 updated by: Roswell Park Cancer Institute

A Randomized, Open-Label Study to Assess the Pain, Toxicity, and Quality of Life Effects of Adding Venlafaxine to the Pain Management Regimen for Patients Treated With Chemoradiation for Head and Neck Cancer

This trial studies how well gabapentin, methadone, and oxycodone with or without venlafaxine hydrochloride work in managing pain in participants with stage II-IV squamous cell head and neck cancer undergoing chemoradiation therapy. Gabapentin may reduce the need for these pain medications if given at the start of radiation therapy. Methadone and oxycodone may help relieve pain caused by cancer. Venlafaxine hydrochloride may prevent or improve pain caused by cancer. It is now yet known whether giving gabapentin, methadone, and oxycodone with venlafaxine hydrochloride will work better in managing pain in participants with squamous cell head and neck cancer undergoing chemoradiation therapy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the pain-reduction effects of adding venlafaxine to a regimen of gabapentin and methadone to control pain during and after chemoradiation.

SECONDARY OBJECTIVES:

I. To assess the effect of venlafaxine hydrochloride (venlafaxine) of the rate of toxicities possibly or probably related to the pain control regimen.

TERTIARY OBJECTIVES:

I. The effect of venlafaxine on other quality of life scores, patient nutrition, hydration status, and opioid requirements during and after chemoradiotherapy (CRT).

OUTLINE: Participants are randomized to 1 of 2 arms.

ARM I: Participants receive gabapentin orally (PO) daily or 3 times a day (TID). Participants may also receive methadone PO TID and oxycodone PO every 8 hours as needed. Treatment continues for up to 12 months in the absence of disease progression or unacceptable toxicity.

ARM II: Participants receive gabapentin, methadone, and oxycodone as in Arm I and venlafaxine PO twice daily (BID) or venlafaxine hydrochloride extended release daily for up to 12 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up at 4 weeks, 3, 6, 9, and 12 months, and then every 6 months for up to 24 months.

Study Type

Interventional

Enrollment (Actual)

62

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients who are eligible for chemoradiation therapy of the head and neck.
  • Patients must have adequate renal function to undergo platinum based chemotherapy. This will mean a baseline creatinine level (Cr) no greater than 1.5 times the upper limit of normal.
  • 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/or retain oral or per tube medication.
  • 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 because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • Any patients prescribed medications for chronic and/or long term pain and/or neuropathy will be excluded, including patients under treatment of a pain specialist or substance-abuse programs. Acute post-op medications are allowed if the patient has discontinued them prior to initiating study.
  • Any patients prescribed a selective serotonin reuptake inhibitor (SSRI), serotonin and norepinephrine reuptake inhibitor (SNRI), tricyclic antidepressant (TCA), monoamine oxidase inhibitors (MAOIs), dextromethorphan, triptan, tryptophan supplements, IV methylene blue, linezolid or any other medication that may increase risk of serotonin syndrome, as deemed by the investigator?s opinion.
  • Any patients with suspected or known, current or recent (within last 5 years) use of cocaine, amphetamines, lysergic acid diethylamide (LSD), 3,4- methylenedioxymethamphetamine (MDMA), or any other drug of abuse that may increase risk of serotonin syndrome, as deemed by the Investigator?s opinion.
  • Any patients with history of suicide-related events, or those exhibiting a significant degree of suicidal ideation.
  • Patients with acute narrow-angle glaucoma.
  • 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 dialysis or with transplanted organs.
  • Patients already enrolled on other studies of systemic pain control agents.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm I (gabapentin, methadone, oxycodone)
Participants receive gabapentin PO daily or TID. Participants may also receive methadone PO TID and oxycodone PO every 8 hours as needed. Treatment continues for up to 12 months in the absence of disease progression or unacceptable toxicity.
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
Given PO
Drug: Oxycodone
Given PO
Other Names:
  • Oxycodone SR
Experimental: Arm II (gabapentin, methadone, oxycodone, venlafaxine)
Participants receive gabapentin, methadone, and oxycodone as in Arm I and venlafaxine PO BID or venlafaxine hydrochloride extended release daily for up to 12 months in the absence of disease progression or unacceptable toxicity.
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
Given PO
Drug: Oxycodone
Given PO
Other Names:
  • Oxycodone SR
Drug: Venlafaxine
Given PO
Drug: Venlafaxine Hydrochloride Extended Release
Given PO
Other Names:
  • Effexor XR
  • Venlafaxine HCl ER

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pain-reduction Effects of Adding Venlafaxine to a Regimen of Gabapentin and Methadone to Control Pain During and After Chemoradiation
Time Frame: Participants were assessed up to 24 months after enrollment, change in score from baseline at week 7 reported
To assess the pain-reduction effects of adding venlafaxine to a regimen of gabapentin and methadone to control pain during and after chemoradiation, per European Organization for Research and Treatment of Cancer (EORTC) Head and Neck Cancer Module (EORTC QLQ-H and N35). The pain scores range between 0 and 100, with higher values represent worse outcomes. The pain scores (mean/standard deviation) of baseline and end of treatment (week 7) are reported.
Participants were assessed up to 24 months after enrollment, change in score from baseline at week 7 reported

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Adverse Events of Pain Regimen Per Cancer Therapy Evaluation Program (CTEP) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE Version 4.0)
Time Frame: Up to 24 months
Toxicities will be tabulated by treatment arm using the maximum grade observed by participant. Possible differences by treatment will be described using odds ratio and 95% confidence interval estimates derived use Mantel?Haenszel methods to account for laterality of the radiation treatment.
Up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Roswell Park Cancer Institute

Investigators

  • Principal Investigator: Anurag Singh, Roswell Park Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 3, 2018

Primary Completion (Actual)

April 19, 2021

Study Completion (Actual)

November 11, 2021

Study Registration Dates

First Submitted

June 11, 2018

First Submitted That Met QC Criteria

June 20, 2018

First Posted (Actual)

July 2, 2018

Study Record Updates

Last Update Posted (Actual)

April 16, 2026

Last Update Submitted That Met QC Criteria

April 13, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • I 61117 (Other Identifier: Roswell Park Cancer Institute)
  • NCI-2018-01055 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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