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High-dose gabapentin versus placebo to prevent opioid use for mouth pain during chemoradiation for head and neck cancer

High-Dose Prophylactic Gabapentin (HOPE) to Prevent Opioid Use for Oral Mucositis Pain During Head and Neck Chemoradiotherapy: A Phase III Clinical Trial

Phase 3 Interventional Alliance for Clinical Trials in Oncology · NCT06992427

This will test whether taking high-dose gabapentin during cisplatin chemoradiation for head and neck cancer helps people avoid needing opioid pain medicine for painful mouth sores.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment228 (estimated)
Ages18 Years and up
SexAll
SponsorAlliance for Clinical Trials in Oncology Academic / other
Drugs / interventionschemotherapy, immunotherapy, radiation
Locations200 sites (Gilbert, Arizona and 199 other locations)
Trial IDNCT06992427 on ClinicalTrials.gov

What this trial studies

This is a randomized, phase III trial comparing prophylactic high-dose gabapentin (titrated to 3600 mg per day) versus placebo in patients receiving cisplatin-based chemoradiation for squamous cell carcinoma of the head and neck. Participants are randomized to receive gabapentin or matching placebo while undergoing standard radiation and chemotherapy, with opioid use, time to first opioid, and patient-reported pain tracked prospectively. The primary outcome is the proportion of patients who do not require opioid medications during treatment; secondary outcomes include time to first opioid use and changes in pain scores through four weeks after treatment. Exploratory analyses examine duration of opioid use and quality-of-life and symptom trajectories over months following therapy.

Who should consider this trial

Good fit: People with squamous cell carcinoma of the head and neck (stages I–IV) who have not had prior head and neck treatment and who are planned for cisplatin-based chemoradiation, can swallow capsules whole, and have no contraindications to gabapentin are ideal candidates.

Not a fit: Patients who are already using opioids recently, cannot take gabapentin (for example due to allergy, dialysis, or organ transplant), have brain metastases, or are not receiving cisplatin-based chemoradiation are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could let more patients avoid starting opioid pain medicines during treatment, reducing opioid side effects and risk of persistent use.

How similar studies have performed: Smaller single-arm and retrospective studies have suggested gabapentin can reduce opioid use and pain in this setting, but large randomized phase III evidence has been limited until now.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Histologic documentation of disease: Squamous cell carcinoma of the head and neck region.

  \* Stage: I-IV
* No prior treatment for head and neck cancer
* Planned treatment with cisplatin-based chemoradiation therapy (weekly or once every 3 weeks \[q 3 week\])
* Able to swallow capsules whole
* No known hypersensitivity to gabapentin or its ingredients
* No patients on dialysis or with transplanted organs
* No prior surgery or radiation for head and neck cancer and/or are being treated for recurrent head and neck cancer. Patients with a history of surgery and radioactive iodine for the treatment of thyroid cancer are eligible. Concurrent cancer therapy for other cancers is not allowed
* No planned surgery or chemotherapy or immunotherapy following 7 weeks of standard chemoradiation treatment
* No known brain metastases
* No nonprescribed use of any opioids (including heroin) within 6 months prior to registration
* No prescribed medications for chronic and/or long-term pain and/or neuropathy, including patients under treatment of a pain specialist or substance abuse programs. Acute post-biopsy medications are allowed if the patient has discontinued them 3 days prior to study registration
* No current treatment with mefloquine
* Age ≥ 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
* Creatinine ≤ 1.5 x upper limit of normal (ULN)
* Not pregnant and not nursing, because this study involves both radiation and chemotherapy. In addition, the genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential, a negative pregnancy test done \< 7 days prior to registration is required. Women must agree to using contraception for the duration of receiving study drugs and for 6 months after completing chemoradiation
* Not taking medications for a psychotic psychiatric illness
* No existing diagnosis of sleep apnea
* No acute narrow-angle glaucoma
* No 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
* No investigational agent within 30 days prior to registration
* No enrollment on other studies of systemic pain control agents
* Language: In order to complete the mandatory patient-completed measures, participants must be able to speak and read English or Spanish
* Patients with impaired decision making are not eligible for study

Exclusion Criteria:

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Where this trial is running

Gilbert, Arizona and 199 other locations

+150 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Head and Neck Squamous Cell CarcinomaStage I Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8Stage II Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8Stage III Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8Stage IV Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.