Clinical trial NCT00719173: Effect of Aprepitant on Cyclophosphamide Pharmacokinetics in Patients With Breast Cancer
Official title: Evaluating the Effect of Aprepitant on Cyclophosphamide Pharmacokinetics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Nausea and Vomiting
Keywords: nausea and vomiting
breast cancer
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-07-21
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Effect of aprepitant on cyclophosphamide and 4-hydroxycyclophosphamide pharmacokinetics as measured by plasma AUC
timeFrame: 05/2005 to 10/2010
Secondary outcomes:
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
Study officials:
affiliation: UNC Lineberger Comprehensive Cancer Center
name: Christine M. Walko, PharmD, BCOP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Walko CM, Combest AJ, Spasojevic I, Yu AY, Bhushan S, Hull JH, Hoskins J, Armstrong D, Carey L, Collicio F, Dees EC. The effect of aprepitant and race on the pharmacokinetics of cyclophosphamide in breast cancer patients. Cancer Chemother Pharmacol. 2012 May;69(5):1189-96. doi: 10.1007/s00280-011-1815-5. Epub 2012 Jan 15.