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

UNC Lineberger Comprehensive Cancer Center

Status and phase: Completed; Phase 1

Conditions: Breast Cancer; Nausea and Vomiting

Treatments: Drug: aprepitant; Other: placebo; Drug: cyclophosphamide

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00719173

UNC-GCRC-2411-ORC

UNC-05-2917

CDR0000600836 (Other Identifier)

LCCC 0514

P30CA016086 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 19 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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19 participants in 2 patient groups

Arm I

Experimental group

Description:

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.

Treatment:

Drug: cyclophosphamide

Other: placebo

Drug: aprepitant

Arm II

Experimental group

Description:

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.

Treatment:

Drug: cyclophosphamide

Other: placebo

Drug: aprepitant