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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Oropharyngeal Cancer; HPV-Related Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Gabapentin

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gabapentin; 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; 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; Other Names: Neurontin
No Intervention: Supportive Care Only; Participants will receive standard best supportive care medications as per their treating physician's recommendation.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: Daniel Haraf, MD, University of Chicago

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2018
• Primary Completion (Actual): November 8, 2022
• Study Completion (Actual): November 8, 2022

Study Registration Dates

• First Submitted: January 26, 2018
• First Submitted That Met QC Criteria: February 5, 2018
• First Posted (Actual): February 6, 2018

Study Record Updates

• Last Update Posted (Actual): July 31, 2024
• Last Update Submitted That Met QC Criteria: July 29, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: oropharyngeal cancer; HPV-related oropharyngeal cancer; HPV-related squamous cell carcinoma; prophylactic gabapentin; Optima II study
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Oropharyngeal Neoplasms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Anti-Anxiety Agents; Anticonvulsants; Antimanic Agents; Gabapentin
• Other Study ID Numbers: IRB17-1550

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.: No