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
Brief Title
High-dose Prophylactic Gabapentin (HOPE) vs. Placebo to Prevent Opioid Use for Oral Mucositis Pain During Concurrent Chemoradiation for Head and Neck Cancer
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.
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.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
773-702-9171
Central Contact Email
cancercontrolprotocols@alliancenctn.org
Completion Date
Completion Date Type
Estimated
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
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:
\-
* 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:
\-
Inclusion 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
* 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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT06992427
Org Class
Other
Org Full Name
Alliance for Clinical Trials in Oncology
Org Study Id
A222301
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
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
Primary Outcomes
Outcome Description
Will be tested using a two-sample test of proportions. Will report the proportion of patients not using opioids within the 7 weeks of CRT in the two arms and the 95% confidence interval (CI) of the difference in the proportions.
Outcome Measure
Need to use opioids during chemoradiation therapy (CRT)
Outcome Time Frame
Up to 7 weeks
Secondary Ids
Secondary Id
NCI-2025-00501
Secondary Outcomes
Outcome Description
Time to first opioid use, defined as the time from randomization to the first occurrence of opioid use during CRT, censoring patients alive and opioid free at CRT completion. Death or disease progression before first opioid use during CRT will be treated as competing events. Cumulative incidence functions will be used to estimate the percentage of patients who experience the competing events within the arms. Differences between the cumulative incidence functions between the arms will be tested for statistical significance using the procedure of Gray. The cumulative incidence percentage at the end of CRT by arm will be reported.
Outcome Time Frame
Up to 9 weeks
Outcome Measure
Time to first opioid use
Outcome Description
Pain score responses of question #5 on the Oral Mucositis Weekly Questionnaire-Head and Neck Cancer (OMWQ-HN) survey at each collected timepoint for each arm. This NRS item asks a respondent to rate their overall mouth and throat soreness during the past week from 0 (no soreness) to 10 (worst possible soreness). Will apply longitudinal modeling of the patient-reported pain scores through four weeks post CRT treatment. Will report each time-specific comparison between arms with a 95% CI.
Outcome Time Frame
Through 4 weeks post CRT (up to 14 weeks)
Outcome Measure
Patient-reported pain scores
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Rafi Kabarriti
Investigator Email
RKABARRI@MONTEFIORE.ORG
Investigator Department
Radiation Oncology
Investigator Sponsor Organization
External
Study Department
Radiation Oncology
Study Division
Radiation Oncology
Categories Mesh Debug
Cancer --- CARCINOMA
Lung & Chest Cancers --- NEOPLASMS, GLANDULAR AND EPITHELIAL
Blood & Bone Marrow Cancers --- NEOPLASMS BY HISTOLOGIC TYPE
Cancer --- NEOPLASMS
Endocrine System Cancers --- NEOPLASMS
Gastrointestinal (GI) Cancers --- NEOPLASMS
Gynecologic Cancers --- NEOPLASMS
Lung & Chest Cancers --- NEOPLASMS
Prostate Cancer --- NEOPLASMS
Endocrine System Cancers --- HEAD AND NECK NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Prostate Cancer --- NEOPLASMS BY SITE
MeSH Terms
SQUAMOUS CELL CARCINOMA OF HEAD AND NECK
CARCINOMA, SQUAMOUS CELL
CARCINOMA
NEOPLASMS, GLANDULAR AND EPITHELIAL
NEOPLASMS BY HISTOLOGIC TYPE
NEOPLASMS
HEAD AND NECK NEOPLASMS
NEOPLASMS BY SITE
GABAPENTIN
COUNTERFEIT DRUGS
RADIOTHERAPY
ACETAMINOPHEN
AMINES
ORGANIC CHEMICALS
GAMMA-AMINOBUTYRIC ACID
AMINOBUTYRATES
BUTYRATES
ACIDS, ACYCLIC
CARBOXYLIC ACIDS
CYCLOHEXANECARBOXYLIC ACIDS
ACIDS, CARBOCYCLIC
CYCLOHEXANES
CYCLOPARAFFINS
HYDROCARBONS, ALICYCLIC
HYDROCARBONS, CYCLIC
HYDROCARBONS
AMINO ACIDS
AMINO ACIDS, PEPTIDES, AND PROTEINS
SUBSTANDARD DRUGS
PHARMACEUTICAL PREPARATIONS
THERAPEUTICS
ACETANILIDES
ANILIDES
AMIDES
ANILINE COMPOUNDS