Effect of Aprepitant on Cyclophosphamide Pharmacokinetics in Patients With Breast Cancer

Phase 1CompletedNCT00719173

UNC Lineberger Comprehensive Cancer Center19 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Breast Cancer Nausea and Vomiting

Interventions

aprepitantDRUG

Given orally

cyclophosphamideDRUG

Given IV

placeboOTHER

Given orally

Eligibility

Sex: ALLMin age: 18 YearsMax age: 120 Years

Medical Language ↔ Plain English

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

Locations (1)

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States

Outcomes

Primary Outcomes

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

Time frame: 05/2005 to 10/2010

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.