PROGRESS Trial - Prophylactic Gabapentin for Relief of Symptoms and Improved Swallowing

Study Overview
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Brief Summary
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Enrollment is only available to patients enrolled on the Optima II study (NCT03107182). The purpose of this trial is to compare rates of opioid use at completion of radiation for patients with Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 2 oral mucositis after receiving definitive nonoperative locoregional therapy with or without prophylactic gabapentin as part of best supportive care for locoregionally-advanced, HPV-related oropharyngeal cancer. Secondary purposes include comparison of total equivalent opioid dosage above baseline opioid use at end of treatment, quality of life metrics, swallowing function, feeding tube dependence, and protocol compliance in patients managed with best support care with or without prophylactic gabapentin. Rates of gabapentin-related side effects and discontinuation will also be investigated.

Detailed Description
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Enrollment is only available to patients enrolled on the Optima II study (NCT03107182). Primary objective: To compare rates of opioid requirement as a function of supportive care in patients experiencing CTCAE grade ≥2 oral mucositis at completion of radiation or chemoradiation as part of OPTIMA II Secondary objectives: To compare total opioid equivalent dose above baseline opioid requirement at end of radiation, quality of life metrics, swallowing function, feeding-tube dependence, and protocol compliance in patients managed with best supportive care with or without prophylactic gabapentin. To investigate rates of gabapentin-related toxicity and discontinuation for patients treated on protocol.

Official Title
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A Phase II Randomized Trial of Prophylactic Gabapentin Plus Best Supportive Care Versus Best Supportive Care Alone for Patients Receiving Induction Chemotherapy Followed by Response-Stratified Locoregional Therapy for Locoregionally-Advanced, HPV-Related Oropharyngeal Cancer: An Optima II Secondary Study

Conditions
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Oropharyngeal Cancer, HPV-Related Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Gabapentin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Enrollment to OPTIMA II trial (NCT03107182) Exclusion Criteria: Ineligible for enrollment to OPTIMA II trial (NCT03107182) Prior gabapentin therapy Creatinine clearance of < 45 mL/minute Documented intolerance, allergy, or hypersensitivity to gabapentin Hemodialysis or peritoneal dialysis

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
Interventional Model Description: Participants receiving radiation therapy as part of the OPTIMA II trial (NCT03107182) will be randomized to receive prophylactic gabapentin plus best supportive care versus best supportive care alone.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gabapentin<br>Participants randomized to this arm will receive gabapentin beginning on evening of the first day of radiation treatment at a dose of 600 mg. Gabapentin will continue to be taken twice a day (morning and evening) for the next 4 days of radiation treatment at increasing doses (up to 900 mg). Participants will continue to receive standard best supportive care medications as per their treating physician's recommendation. | Drug: Gabapentin<br>* Gabapentin taken as follows: Day 1 (evening): 600 mg Day 2 (morning): 600 mg Day 2 (evening): 600 mg Day 3 (morning): 600 mg Day 3 (evening): 900 mg Day 4 (morning): 900 mg Day 4 (evening): 900 mg Day 5 (morning): 900 mg Day 5 (noon): 900 mg Day 5 (evening): 900 mg<br>* Other names: Neurontin;|
| No Intervention: Supportive Care Only<br>Participants will receive standard best supportive care medications as per their treating physician's recommendation. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of opioid use at end of radiation treatment | Comparison of opioid use as part of best supportive care in patients with CTCAE grade ≥ 2 oral mucositis at the end of radiation treatment given as part of OPTIMA II study. | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total opioid dosage during radiation treatment | Comparison of total opioid dosage given as part of best supportive care in patients with CTCAE grade ≥ 2 oral mucositis at the end of radiation treatment given as part of OPTIMA II study. | 5 days | 
| Differences in head and neck symptoms | Measured by changes in patient reported head and neck specific symptoms | 24 months | 
| Differences in overall quality of life | Measured by changes in patient reported symptoms | 24 months | 
| Differences in chemotherapy-induced peripheral neuropathy symptoms | Measured by patient reported symptoms | 24 months | 
| Swallowing Function | Normal Within functional limits: abnormal oral or pharyngeal stage but able to eat regular diet; no modifications or swallowing precautions Mild impairment: mild dysfunction in oral or pharyngeal stage, requires modified diet; no therapeutic swallowing precautions Mild-moderate impairment: mild dysfunction in oral and pharyngeal stage, requires modified diet and therapeutic swallowing precautions Moderate impairment: moderate dysfunction in oral or pharyngeal stage, aspiration noted on exam, requires modified diet and swallowing precautions Moderate-severe dysfunction: moderate dysfunction in oral or pharyngeal stage, aspiration noted on exam, requires modified diet and swallowing precautions; requires primary enteral feeding support Severe impairment: severe dysfunction with significant aspiration or inadequate oropharyngeal transit to esophagus, NPO, requires primary enteral feeding support | 12 weeks | 
| Feeding Tube Dependence | Assessment of rates of feeding tube dependence during and after radiation treatment | 24 months | 
| Treatment Delays | Determine rate of unplanned radiation treatment delays. | 7 weeks | 
| Side Effects | Determine rate of gabapentin related side effects as per CTCAE v4. | 13 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HPV-related oropharyngeal cancer, oropharyngeal cancer, HPV-related squamous cell carcinoma, prophylactic gabapentin, Optima II study