NRR: Effect of Aprepitant on Cyclophosphamide Pharmacokinetics in Patients With Breast Cancer

Sponsor

UNC Lineberger Comprehensive Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00719173

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arms

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Nausea and Vomiting	Drug: aprepitant Drug: cyclophosphamide Other: placebo	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

19 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Evaluating the Effect of Aprepitant on Cyclophosphamide Pharmacokinetics

Study Start Date :

Aug 1, 2005

Actual Primary Completion Date :

Oct 1, 2010

Actual Study Completion Date :

Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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 as in arm II.	Drug: aprepitant Given orally Drug: cyclophosphamide Given IV Other: placebo Given orally
Experimental: 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 as in arm I.	Drug: aprepitant Given orally Drug: cyclophosphamide Given IV Other: placebo Given orally

Arm

Intervention/Treatment

Experimental: 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 as in arm II.

Drug: aprepitant

Given orally

Drug: cyclophosphamide

Given IV

Other: placebo

Given orally

Experimental: 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 as in arm I.

Drug: aprepitant

Given orally

Drug: cyclophosphamide

Given IV

Other: placebo

Given orally

Outcome Measures

Primary Outcome Measures

Effect of aprepitant on cyclophosphamide and 4-hydroxycyclophosphamide pharmacokinetics as measured by plasma AUC [05/2005 to 10/2010]
Cyclophosphamide, 4-OH cyclophosphamide, and DCE PK with and without aprepitant

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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