Gabapentin in Preventing Nausea and Vomiting in Patients Receiving Chemotherapy

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 3

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

Treatments: Drug: gabapentin; Drug: dexamethasone; Other: placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00880191

NCCTG-N08C3

NCI-2009-01110 (Registry Identifier)

CDR0000634077 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 430 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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430 participants in 2 patient groups

Arm I

Experimental group

Description:

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.

Treatment:

Drug: gabapentin

Drug: dexamethasone

Arm II

Experimental group

Description:

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.

Treatment:

Other: placebo

Drug: dexamethasone