Clinical trial NCT06992427: High-dose Prophylactic Gabapentin (HOPE) vs. Placebo to Prevent Opioid Use for Oral Mucositis Pain During Concurrent Chemoradiation for Head and Neck Cancer
Official title: High-Dose Prophylactic Gabapentin (HOPE) to Prevent Opioid Use for Oral Mucositis Pain During Head and Neck Chemoradiotherapy: A Phase III Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Head and Neck Squamous Cell Carcinoma
Stage I Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8
Stage II Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8
Stage III Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8
Stage IV Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2025-05-28
Enrollment: 228
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: This phase III trial tests if gabapentin can prevent the need for opiate pain medication for mouth sores (oral mucositis) in patients undergoing treatment with chemotherapy and radiation for squamous cell carcinoma of the head and neck region. Oral mucositis is a common side effect of radiation treatment and can cause severe pain, dysphagia, and weight loss resulting in feeding tube placement, worse health-related quality of life, treatment interruptions, unplanned hospitalizations, and significant financial burden. Mucositis pain is often treated with opioid pain medications which do provide pain relief but have many known side effects not limited to mental clouding, constipation, fatigue, endocrinopathy, neurotoxicity, sleep-disordered breathing, and most distressingly persistent opioid use. Gabapentin may help relieve pain from oral mucositis caused by radiation while also reducing the need for opiate pain medications for patients receiving chemotherapy and radiation for squamous cell carcinoma of the head and neck region

Detailed description: PRIMARY OBJECTIVE:

I. To determine whether prophylactic high dose gabapentin, titrated to a dose of 3600 mg (1200 mg three times per day \[TID\]), is superior to placebo in increasing the proportion of patients not needing opiates while undergoing chemoradiation therapy.

SECONDARY OBJECTIVES:

I. To determine whether prophylactic high dose gabapentin is superior to placebo in prolonging the time to first opioid use while undergoing chemoradiation therapy.

II. To determine whether prophylactic high dose gabapentin is superior to placebo in improving patient reported pain scores using the 0-10 numerical rating scale (NRS) from baseline to 4 weeks after the end of chemoradiation therapy.

EXPLORATORY OBJECTIVES:

I. To explore the duration of opioid use from the time of initiation to cessation by arm as well as describe the proportion of patients remaining on opioids at 3 months, 6 months, and 1 year by arm.

II. To explore the trajectory of patient reported symptom and quality of life outcomes using the Oral Mucositis Weekly Questionnaire (OMWQ) by arm.

III. To explore the trajectory of patient reported symptom and quality of life outcomes using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-30 (EORTC QLQ-30) by arm.

IV. To explore the trajectory of patient reported symptom and quality of life outcomes using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck-43 (EORTC QLQ-H\&N43) by arm.

V. To evaluate the adverse event profiles of prophylactic high dose gabapentin versus placebo.

VI. To assess the tolerance of high dose gabapentin. VII. To explore the trajectory of patient health using patient body mass index (BMI) and creatinine, absolute neutrophil count (ANC) as routinely obtained by arm.

VIII. To describe the incidence of feeding tube requirement during and after chemoradiation therapy by arm.

IX. To describe the dose of prescribed opioids standardized using the Morphine Milligram Equivalent calculator by arm.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Starting by radiation treatment 8, patients receive placebo orally (PO) once daily (QD) on day 1, twice daily (BID) on day 2, then three times daily (TID) starting day 3 onward. Patients also receive standard of care radiation, chemotherapy and pain medications. Treatment with placebo continues in the absence of disease progression or unacceptable toxicity, until the symptoms of oral mucositis and other treatment effects begin to resolve and other pain medications has been stopped. Patients then continue to receive placebo TID for 9 additional days, at sequentially smaller doses, then BID for 1 day and QD for one day before stopping. Patients undergo blood sample collection throughout the study.

ARM II: Starting by radiation treatment 8, patients receive gabapentin PO QD on day 1, BID on day 2, then TID starting day 3 onward. Patients also receive standard of care radiation, chemotherapy and pain medications. Treatment with gabapentin continues in the absence of disease progression or unacceptable toxicity, until the symptoms of oral mucositis and other treatment effects begin to resolve and other pain medications has been stopped. Patients then continue to receive gabapentin TID for 9 additional days, at sequentially smaller doses, then BID for 1 day and QD for one day before stopping. Patients undergo blood sample collection throughout the study.

After completion of study treatment, patients are followed up at 4 weeks, 3 months and 6 months after the last dose of chemoradiation therapy.

Eligibility 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:

-

Primary outcomes:
measure: Need to use opioids during chemoradiation therapy (CRT)
timeFrame: Up to 7 weeks
Secondary outcomes:
measure: Time to first opioid use
timeFrame: Up to 9 weeks
measure: Patient-reported pain scores
timeFrame: Through 4 weeks post CRT (up to 14 weeks)
Other outcomes:
measure: Need to use opioids during CRT by sex
timeFrame: Up to 7 weeks
measure: Need to use opioids during CRT by race
timeFrame: Up to 7 weeks
measure: Need to use opioids during CRT by ethnicity
timeFrame: Up to 7 weeks
measure: Duration of opioid use
timeFrame: Though 4 weeks post CRT (up to 14 weeks)
measure: Global health
timeFrame: Through 4 weeks post CRT (up to 14 weeks)
measure: Patient reported oral mucositis symptoms.
timeFrame: Through 4 weeks post CRT (up to 14 weeks)
measure: Mouth and throat soreness
timeFrame: Through 4 weeks post CRT (up to 14 weeks)
measure: Impact of mouth and throat soreness on patient function
timeFrame: Through 4 weeks post CRT (up to 14 weeks)
measure: Incidence of symptoms or problems
timeFrame: Through 4 weeks post CRT (up to 14 weeks)
measure: Incidence of adverse events (AE)
timeFrame: Up to approximately 2 years
measure: Tolerance of gabapentin
timeFrame: Up to the 9 weeks
measure: Body mass index
timeFrame: Up to the 9 weeks
measure: Creatinine
timeFrame: Up to the 9 weeks
measure: Absolute neutrophil count
timeFrame: From baseline to the completion of CRT
measure: Dose of prescribed opioids
timeFrame: Up to 7 weeks.
measure: Incidence of Feeding Tube
timeFrame: Through 4 weeks post CRT (up to 14 weeks)
Locations:
Study officials:
References: