Gabapentin in Preventing Nausea and Vomiting in Patients Receiving Chemotherapy

Study Overview
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Brief Summary
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RATIONALE: Gabapentin may prevent or reduce delayed nausea and vomiting caused by chemotherapy. It is not yet known whether gabapentin is more effective than a placebo in preventing nausea and vomiting. PURPOSE: This randomized phase III trial is studying the side effects of gabapentin and to see how well it works compared with a placebo in preventing nausea and vomiting in patients receiving chemotherapy.

Detailed Description
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OBJECTIVES: To evaluate the effectiveness of gabapentin in controlling delayed chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy as defined by the percentage of complete responders (no emetic episodes and no rescue medication) on days 2 through 6 (five days after receipt of highly emetogenic chemotherapy) compared to an effective prophylactic regimen. To evaluate the effectiveness of gabapentin in controlling delayed CINV in patients receiving highly emetogenic chemotherapy as defined by the percentage of complete responders (no emetic episodes, no more than mild nausea, and no rescue medication) on days 2 through 6 compared to an effective prophylactic regimen. To compare the effectiveness of these regimens in controlling acute CINV on day 1 of treatment in these patients. To compare the use of rescue agents in these patients. To determine the tolerability of gabapentin in these patients. To evaluate the effect of gabapentin for delayed chemotherapy-induced nausea and vomiting on symptom distress and functional abilities in these patients. To compare alternative endpoints and methods for assessing nausea and vomiting and to determine how these measures compare to patient's satisfaction with symptom control, distress and function. OUTLINE: This is a multicenter study. Patients are stratified according to gender, age (< 50 years vs > 50 years), history of alcoholism (yes vs no), and history of motion sickness or history of pregnancy induced nausea/vomiting (yes vs no). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral dexamethasone with 5HT3 receptor antagonist and oral gabapentin once daily on day 1 of chemotherapy. Patients then receive oral dexamethasone twice daily with or without 5HT3 receptor antagonist on days 2-4, and oral gabapentin either two or three times daily on days 2-5 of chemotherapy. Arm II: Patients receive oral dexamethasone with 5HT3 receptor antagonist and oral placebo once daily on day 1 of chemotherapy. Patients then receive oral dexamethasone twice daily with or without 5HT3 receptor antagonist on days 2-4, and oral placebo either two or three times daily on days 2-5 of chemotherapy. Patients complete a Functional Living Index - Emesis questionnaire, an overall satisfaction survey, and a side effect experience diary at baseline and on day 6. Patients also complete a nausea and vomiting diary at baseline and periodically during study therapy.

Official Title
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Phase III Double-Blind, Placebo-Controlled Study of Gabapentin for the Prevention of Delayed CINV (Chemotherapy Induced Nausea and Vomiting) in Patients Receiving Highly Emetogenic Chemotherapy

Conditions
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Nausea and Vomiting, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: dexamethasone
* Drug: gabapentin
* Other: placebo


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Scheduled to receive highly emetogenic chemotherapy May be scheduled to receive prophylactic treatment for acute nausea and vomiting with a 5HT3 antagonist and dexamethasone 20 mg on day 1 of chemotherapy treatment May be scheduled to receive multiple day chemotherapy regimens as long as the chemotherapy drugs given on the subsequent days have mild or no emetogenic potential Chemotherapy schedules must allow at least 7 days rest between courses involving administration of highly emetogenic chemotherapy No primary CNS malignancy and/or CNS metastasis PATIENT CHARACTERISTICS: Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Life expectancy ≥ 3 months Creatinine ≤ 1.5 times upper limit of normal within the past 30 days Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Ability to complete questionnaire(s) by his/herself or with assistance Able to swallow pills No epilepsy or seizure history No gastrointestinal obstruction, active peptic ulcer disease, or uncontrolled heartburn No history of nausea and/or vomiting related to any kind of chemotherapy No nausea or vomiting within the past 3 days No history of allergic or other adverse reaction to gabapentin or pregabalin PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior moderate or highly emetogenic chemotherapy No prior or concurrent aprepitant or any other NK-1 receptor antagonist At least 1 months since prior and no concurrent gabapentin, pregabalin, or other anticonvulsants At least 7 days since prior and no concurrent pelvic or abdominal radiotherapy At least 3 days since prior antiemetics No concurrent or planned use of lorazepam, diphenhydramine, eszopiclone, and/or dronabinol during the 6 days of this study, except for treatment of breakthrough nausea and vomiting

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive oral dexamethasone with 5HT3 receptor antagonist and oral gabapentin once daily on day 1 of chemotherapy. Patients then receive oral dexamethasone twice daily with or without 5HT3 receptor antagonist on days 2-4, and oral gabapentin either two or three times daily on days 2-5 of chemotherapy. | Drug: dexamethasone<br>* Given orally<br>Drug: gabapentin<br>* Given orally<br>|
| Experimental: Arm II<br>Patients receive oral dexamethasone with 5HT3 receptor antagonist and oral placebo once daily on day 1 of chemotherapy. Patients then receive oral dexamethasone twice daily with or without 5HT3 receptor antagonist on days 2-4, and oral placebo either two or three times daily on days 2-5 of chemotherapy. | Drug: dexamethasone<br>* Given orally<br>Other: placebo<br>* Given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of Percentage of Complete Responders | Complete response being defined as no emetic episodes and no use of rescue therapy for days 2 through 6. If a patient does not complete the study or does not provide complete data, they will be assumed to be a non-responder. | Days 2 through 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response | The primary analysis described above was repeated using a slightly different alternate definition of complete response: no emetic episodes, no more than a mean of 2.5 on the nausea numeric analogue scale (0 - 10 (As bad as it could be)), and no rescue agents. | Days 2-6 | 
| Comparison of Percentages of Complete Responders on Day 1, vs. Days 1 Through 6 vs. Days 2 Through 6. | The percentages of complete responders on day 1, vs. days 1 through 6 vs. days 2 through 6 will be compared between arms. Complete response being defined as no emetic episodes and no use of rescue therapy. If a patient does not complete the study or does not provide complete data, they will be assumed to be a non-responder. | Days 1 through 6 | 
| Comparison of the Percentage of Patients Experiencing Emetic Episodes and the Percentage Needing Rescue Agents | The percentage of patients experiencing emetic episodes and the percentage needing rescue agents was compared between groups. | Days1 through 6 | 
| Comparison of Sum of the Daily Distress Questions as Well as the Individual Daily Responses | The sum of the daily distress questions as well as the individual daily responses from the Nausea and Vomiting Diary (NVD) on a 0-10 scale (Lower score is better) will be compared. | Days 1 through 6 | 
| Level of Satisfaction for the Control of Nausea. | Level of satisfaction for the control of nausea with the mean severity of nausea over the six days in the diary (on a 0 - 10 scale, higher the better) as well as the nausea subscale on the Functional Living Index - Emesis (FLIE) questionnaire ( 1-7 scale, lower the better) | Days 1 through 6 | 
| Comparison of Daily Complete Response Endpoints | Daily complete response is defined as no emetic episodes and no use of rescue therapy. | Days 1 through 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nausea and vomiting, unspecified adult solid tumor, protocol specific