Gemcitabine Pharmacokinetics After Preoperative Chemoradiation Therapy

Surgery:

If you agree to take part in this study, your surgery will be performed in the same way as it
would be even if you were not taking part in this study. You will sign a separate consent
form for surgery. The length of the surgery and the time you are under anesthesia will not be
changed by taking part in the study.

During surgery, you will have routine procedures to learn if the disease has spread to other
areas. If the disease has spread beyond the pancreas, surgical removal will not be possible.

If there are no signs of spread or other reasons the cancer cannot be removed, the surgeon
will begin the process of removing the disease.

Study Drug Administration:

You will receive gemcitabine by vein during surgery. Gemcitabine will be given through an
infusion catheter that is placed in your arm or chest in the operating room after you are
asleep.

The infusion catheter is a standard-of-care procedure for all participants who are having
this surgery. You will be asked to sign a separate consent form for the infusion catheter.

The infusion will take either 50 or 75 minutes, depending upon when you joined the study. The
first 5 participants will receive gemcitabine over 50 minutes and the rest of the
participants will receive gemcitabine over 75 minutes.

Blood and Tissue Collection:

Up to 8 blood samples (about 1 tablespoon each time) will be drawn over 70-95 minutes for
pharmacokinetic (PK) testing on the day of surgery. PK testing measures the levels of study
drug in your blood at different time points. The blood will also be used for biomarker
testing. Biomarkers are chemical markers found in the blood and tissue that may be related to
your reaction to the study drug.

Some of the tumor tissue and normal tissue removed during surgery will be collected to learn
if gemcitabine is able to enter the tissue cells and for biomarker testing.

Length of Participation:

If for any reason during the surgery the surgeon decides that removal of the pancreas is not
possible, you will not receive gemcitabine and your participation in this study will end.

Your active participation in this study will be over once you have had surgery and completed
the follow-up.

Follow-Up:

One (1) time each day while you are in the hospital recovering from the surgery and then at
the time of a routine clinic visit or by phone call at least 1 time a week, for up to 30 days
after surgery, you will be asked if you have had any side effects.

This is an investigational study. Gemcitabine is FDA approved and commercially available for
the treatment of pancreatic cancer. Its use during surgery is investigational.

Up to 40 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Cytologic or histologic proof of adenocarcinoma of the pancreas is required. Patients
with Islet cell tumors are not eligible.

2. Patients do not have known metastases.

3. Patients must have potentially resectable or borderline resectable pancreatic cancer
and have agreed to undergo surgical resection at MD Anderson Cancer Center if
operable. They will have undergone staging (physical examination, chest x-ray,
contrast enhanced CT or MRI (if CT contraindicated) and/or angiogram) to determine
resectability.

4. Patients have completed radiation and chemotherapy with either fluoropyrimidines (5-FU
or capecitabine) or gemcitabine as a radiosensitizing agent as part of their
preoperative therapy. Previous systemic chemotherapy alone is not allowed.
Preoperative therapy will be completed at least 4 weeks prior to surgery.

5. Patients with Karnofsky performance status > 70 are eligible.

6. There will be no upper age restriction. Patients less than 18 years of age are
excluded from the protocol because adenocarcinoma of the pancreas is rarely seen in
the pediatric population.

7. Adequate renal and bone marrow function: Leukocytes >= 3,000/uL; Absolute neutrophil
count >= 1,500/uL; Platelets >= 100,000/Ul; Serum creatinine <= 2.0 mg/dL; Creatinine
clearance >= 60 ml/min (calculated by the Cockcroft -Gault equation)

8. Adequate Hepatic function (endoscopic or percutaneous drainage as needed): Total
bilirubin < = 3 X institutional upper limits of normal (ULN); AST (SGOT)/ALT (SGPT) <=
5 X institutional ULN

9. Patients must have no fever or evidence of infection or other coexisting medical
condition that would preclude administration of gemcitabine. Patients with
uncontrolled congestive heart failure, unstable angina and myocardial infarction
within 3 months will be excluded.

10. Patient is not pregnant. Women of childbearing potential (i.e., women who are
pre-menopausal or not surgically sterile) must use acceptable contraceptive methods
(abstinence, intrauterine device [IUD], oral contraceptive or double barrier device)
and refrain from breast-feeding, as specified in the informed consent.

11. Patients must sign a study-specific consent form.

Exclusion Criteria:

1. Major cardiovascular or pulmonary comorbidity that precludes use of general anesthesia
(NYHA [New York Heart Association] Class III and IV).

2. Identification of metastatic disease.

3. Patients with a known hypersensitivity to Gemcitabine.

4. Pregnant women

5. Inability to comply with study and/or follow-up procedures.

6. Patients < 18 years of age.