Aprepitant in Preventing Nausea and Vomiting in Patients Undergoing Chemotherapy and Radiation Therapy for Pancreatic Cancer

PRIMARY OBJECTIVES:

I. Discern the gastrointestinal toxicities associated with 5-FU (fluorouracil)/Gemcitabine
(gemcitabine hydrochloride) chemotherapy when combined with upper abdominal radiation
therapy.

II. Determine if the addition of prophylactic Aprepitant/5HT-3/Dexamethasone therapy to
standard chemoradiation for patients with pancreatic cancer results in less nausea and
vomiting when compared to historical controls.

SECONDARY OBJECTIVES:

I. To determine the impact of prophylactic Aprepitant/5HT-3/Dexamethasone therapy on the
impact of emesis on daily living, as measured using the MASCC Antiemesis (MAT) tool.

OUTLINE:

CHEMORADIOTHERAPY: Patients undergo radiation therapy once daily on days 1-5 for 5.5 weeks.
Patients also receive gemcitabine hydrochloride intravenously (IV) over 30 minutes once
weekly and either fluorouracil IV continuously or capecitabine orally (PO) twice daily on
days 1-5.

PROPHYLACTIC THERAPY: Beginning 1 hour before chemoradiotherapy, patients receive aprepitant
PO on days 1-3. Treatment repeats every 7 days for 5.5 weeks in the absence of disease
progression or unacceptable toxicity.

CONSOLIDATION CHEMOTHERAPY: Two to four weeks after completion of chemoradiotherapy and
prophylactic therapy, patients without disease progression or a declining performance status
receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every
21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

Inclusion Criteria:

- Histologic or cytologic diagnosis of carcinoma arising from the pancreas

- Resected or unresectable pancreatic cancer, potentially resectable, or resectable
(neoadjuvant) disease (stage II and III); stage IV patients with symptomatic back pain
requiring palliation are also eligible at the discretion of the Principal Investigator
(PI); resected patients, i.e. - "Whipple" of biliary ductal cancers are also eligible
at the discretion of the PI

- Performance status 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale

- Evidence of disease; this can be measurable, evaluable, or nonmeasurable

- Estimated life expectancy of at least 12 weeks

- Absolute neutrophil (segmented and bands) count (ANC) >= 1.5 X 10^9/L

- Platelets >= 100 X 10^9/L

- Hemoglobin >= 9 g/dL

- Bilirubin =< 1.5 times upper limit of normal (ULN)

- Alkaline phosphatase (AP) =< 3.0 ULN ( AP =< 5 x ULN is acceptable if liver has tumor
involvement)

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 ULN (AST
and ALT =< 5 x ULN is acceptable if liver has tumor involvement)

- Albumin >= 3.0 g/dL

- Signed informed consent from patient

- Male and female patients with reproductive potential must use an approved
contraceptive method (e.g., intrauterine device, birth control pills, or barrier
device) during and for 3 months after the study

Exclusion Criteria:

- Active infection (at the discretion of the investigator)

- Neuroendocrine tumor of the pancreas

- Documented brain metastasis; brain imaging in symptomatic patients is required to rule
out metastases, but not required in asymptomatic patients

- Pregnancy

- Breast feeding

- Serious concomitant systemic disorders incompatible with the study (at the discretion
of the investigator)

- Use of any investigational agent within 4 weeks before enrollment into the study

- Significant cardiovascular disease in the form of abnormal electrocardiogram (ECG)
coupled with clinical features of recent or recurrent cardiac disease (including
myocardial infarction, angina or hypertension)

- Prior treatment with chemotherapy for pancreatic cancer

- Clinically significant effusions (pleural or peritoneal) that cannot be drained