Effect of Aprepitant on Cyclophosphamide Pharmacokinetics in Patients With Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Antiemetic drugs, such as aprepitant, may help lessen or prevent nausea and vomiting in patients undergoing chemotherapy. PURPOSE: This randomized clinical trial is studying aprepitant to see how well it works compared to placebo in preventing nausea and vomiting in patients undergoing chemotherapy for breast cancer.

Detailed Description
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OBJECTIVES: Primary To evaluate the effect of aprepitant on cyclophosphamide and 4-hydroxycyclophosphamide pharmacokinetics as measured by plasma AUC in patients with breast cancer. Secondary To evaluate total control of nausea and vomiting, as defined by no vomiting episodes and no use of rescue medication, 72 hours after courses 1 and 2 of chemotherapy. OUTLINE: Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive aprepitant 125 mg orally once daily on day 1 and 80 mg orally once daily on days 2 and 3. Beginning 1 hour after receiving aprepitant, patients receive an infusion of cyclophosphamide on day 1. During course 2, patients crossover and receive treatment (placebo) as in arm II. Arm II: Patients receive a placebo 125 mg orally once daily on day 1 and 80 mg orally once daily on days 2 and 3. Beginning 1 hour after receiving the placebo, patients will receive an infusion of cyclophosphamide infusion on day 1. During course 2, patients crossover and receive treatment (aprepitant) as in arm I. Patients complete a diary documenting nausea and vomiting on days 1, 2, and 3 of both courses. Patients also complete The Functional Living Index-Emesis (FLIE) questionnaire documenting compliance, rescue antiemetic therapy, and any adverse effects and record them in the diary for each course. Information in the patient's diary is obtained by the coordinator via telephone on day 4 of each course. Patients undergo blood sample collection periodically for pharmacokinetic studies via high performance liquid chromatography.

Official Title
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Evaluating the Effect of Aprepitant on Cyclophosphamide Pharmacokinetics

Conditions
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Breast Cancer, Nausea and Vomiting

Intervention / Treatment
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* Drug: aprepitant
* Drug: cyclophosphamide
* Other: placebo


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of breast cancer Planning to receive cyclophosphamide 600 mg/m²-1,000 mg/m² IV infusion No cyclophosphamide dose change between courses 1 and 2 PATIENT CHARACTERISTICS: Life expectancy ≥ 2 months ANC ≥ 1,500/μL Platelet count ≥ 100 x 10^9/L Hemoglobin ≥ 9.0 g/dL Serum creatinine ≤ 1.5 mg/dL AST/ALT ≤ 2 times upper limit of normal Not pregnant or nursing No contraindication to aprepitant PRIOR CONCURRENT THERAPY: See Disease Characteristics No concurrent medications that are CYP3A4 substrates, inhibitors, and/or inducers, with the exception of the dexamethasone contained as part of the standard antiemetic regimen

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive aprepitant 125 mg orally once daily on day 1 and 80 mg orally once daily on days 2 and 3. Beginning 1 hour after receiving aprepitant, patients receive an infusion of cyclophosphamide on day 1. During course 2, patients crossover and receive treatment as in arm II. | Drug: aprepitant<br>* Given orally<br>Drug: cyclophosphamide<br>* Given IV<br>Other: placebo<br>* Given orally<br>|
| Experimental: Arm II<br>Patients receive a placebo 125 mg orally once daily on day 1 and 80 mg orally once daily on days 2 and 3. Beginning 1 hour after receiving the placebo, patients will receive an infusion of cyclophosphamide infusion on day 1. During course 2, patients crossover and receive treatment as in arm I. | Drug: aprepitant<br>* Given orally<br>Drug: cyclophosphamide<br>* Given IV<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 |
| --- | --- | --- |
| Effect of aprepitant on cyclophosphamide and 4-hydroxycyclophosphamide pharmacokinetics as measured by plasma AUC | Cyclophosphamide, 4-OH cyclophosphamide, and DCE PK with and without aprepitant | 05/2005 to 10/2010 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nausea and vomiting, breast cancer