Fosaprepitant Dimeglumine and Granisetron Transdermal System in Preventing Nausea and Vomiting in Patients With Breast Cancer Undergoing Chemotherapy

PRIMARY OBJECTIVE:

I. To evaluate the efficacy of the combination of fosaprepitant (fosaprepitant dimeglumine)
and granisetron transdermal system in the prevention of acute and delayed chemotherapy
induced nausea and vomiting in breast cancer patients undergoing adjuvant or neoadjuvant
chemotherapy.

SECONDARY OBJECTIVE:

I. To evaluate the safety of the combination of fosaprepitant and granisetron transdermal
system in breast cancer patients undergoing adjuvan or neoadjuvant chemotherapy.

EXPLORATORY OBJECTIVE:

I. To explore the use of single nucleotide polymorphisms (SNPs) in the 5âhydroxytryptamine-3
(5HT3) and neurokinin-1 (NK-1) receptors as potential markers of efficacy.

OUTLINE: Patients receive granisetron transdermal system patch 24-48 hrs before the
initiation of chemotherapy. Patients wear the granisetron transdermal system patch for 7
days. Patients receive fosaprepitant dimeglumine intravenously (IV) over 15 minutes on day 1
of chemotherapy. Treatment repeats every 2 or 3 weeks for up to 4 courses in the absence of
unacceptable toxicity.

Inclusion Criteria:

- Patients with histologically confirmed breast cancer scheduled to receive chemotherapy
with doxorubicin and cyclophosphamide (adjuvant or neoadjuvant)

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

- Projected life expectancy of at least 3 months

- Provision of informed consent prior to any study-related procedures

- Negative pregnancy test for women of childbearing potential

- Absolute neutrophil count (ANC) >= 1500/mm^3

- Platelet count >= 100,000 cells/mm^3

- Hemoglobin >= 9.0g/dL

- Serum creatinine =< 1.5 mg/dl

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 X upper
limit of normal (ULN)

- Alkaline phosphatase =< 2.5 X upper limit of normal; in patients with bone metastasis
and no evidence of liver metastasis and bilirubin =< upper limit of normal an alkaline
phosphatase =< 5 ULN will be allowed

- Serum bilirubin =< 1.0 mg/dL

- No other concomitant therapy directed at the cancer is allowed

Exclusion Criteria:

- Allergy or intolerance to 5HT3 or NK-1 antagonists and dexamethasone

- Use of another antiemetic agent (5HT3 antagonists, phenothiazines, butyrophenones,
cannabinoids, metoclopramide, or corticosteroids) within 72 hours prior to day 1 of
the study

- Use of anticoagulant agent (Warfarin, Coumadin, Jantoven, Marevan, Lawarin, Waran, or
Warfant)

- An episode of vomiting or retching within 24 hours before the start of the initial
treatment with chemotherapy

- Severe concurrent illness other than neoplasia

- Gastrointestinal obstruction or an active peptic ulcer

- Patients who are pregnant or breast feeding because aprepitant may be harmful to the
developing fetus and newborn