Tissue Pharmacokinetics of Intraoperative Gemcitabine in Resectable Adenocarcinoma of the Pancreas

The Study Drugs:

Gemcitabine is a drug used to treat pancreatic cancer. However, there are no studies that
show that gemcitabine is able to enter pancreatic cancer cells.

Losartan is a drug that lowers blood pressure. It also may increase the amount of gemcitabine
that reaches the cancer cells. Participant may be asked to take this drug before
participant's surgery.

Before Surgery:

If participant is found to be eligible and participant agrees to take part in this study, the
following tests will be done before participant's surgery:

- Participant will have a routine CT (computed tomography) scan and a research MRI
(magnetic resonance imaging) of participant's abdomen to check the status of the
disease.

- Blood (about 3-4 teaspoons) will be drawn for biomarker testing.

Participant may be asked to take losartan for 2-4 two to four weeks before participant's
surgery (described below).

Surgery:

Participant's surgery will be performed in the same way as it would be even if participant
was not taking part in this study. Participant will sign a separate consent form for surgery.
The length of the surgery and the time participant is under anesthesia are not changed by
taking part in the study.

To measure how much gemcitabine enters pancreas cancer cells, participants who are having
their pancreatic cancer removed by surgery will receive an infusion of gemcitabine during the
surgery. Some of the pancreatic cancer tissue removed then will be checked to learn if
gemcitabine is found in the cancer cells.

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

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

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

Gemcitabine Infusion:

Participant will receive an infusion of gemcitabine just before the surgeon begins to remove
the cancer. Gemcitabine will be given through an infusion catheter that is placed in the
operating room after participant is asleep. The infusion will take over 100 minutes. The
infusion catheter is not required for the study but is a standard of care procedure for all
participants who are having pancreatic cancer surgery. Participant will sign a separate
consent form for the infusion catheter.

Losartan Administration:

If participant is asked to take losartan, participant will take 1 tablet by mouth every day
for up to 4 weeks before participant's surgery. After Week 1, the study staff will tell
participant if participant's dose will stay the same or increase, based on any side effects
that participant may have.

Blood and Tissue Collection:

Up to 10 blood samples (about 1 tablespoon each time) will be drawn during surgery starting
before the gemcitabine infusion begins and at the end of surgery. The blood samples are used
to measure the levels of gemcitabine in participant's blood at different time points. This is
called pharmacokinetic (PK) testing. The blood will also be used for biomarker testing.
Biomarkers are chemical "markers" in the blood/tissue that may be related to participant's
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 Study:

Participant's active participation in this study will be over once participant has had
surgery and completed the follow-up. The research team will continue to collect information
on participant for 30 days after surgery (or until participant is no longer having side
effects).

Follow-Up:

The study team will follow participant's health status for 30 days after surgery to check if
participant is having any side effects from gemcitabine. This follow-up will be done daily
while participant is in the hospital recovering from the surgery. Follow-up will also occur
at the time of a routine clinic visit, or by phone call at least once weekly. These calls
should last about 5 minutes each.

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

Losartan is FDA approved and commercially available for the treatment of high blood pressure
and diabetic nephropathy. It is not approved for the treatment of pancreatic cancer.

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 pancreatic cancer and have agreed to undergo
surgical resection at M D Anderson Cancer Center. They will have undergone staging
(physical examination, chest x-ray, contrast enhanced CT or MRI (if CT
contraindicated) and/or angiogram to determine resectability. Potentially resectable
is defined as:No extra-pancreatic disease; No evidence (on CT/MRI) of tumor extension
to the celiac axis or SMA; No evidence (CT/MRI or angiogram) of occlusion of the SMV
or SMPV confluence.

4. Patients with a Karnofsky performance status greater than 70 are eligible.

5. 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.

6. 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.

7. 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.

8. 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.

9. Patient is not pregnant. Women of childbearing potential (defined as those who have
not undergone a hysterectomy or who have not been postmenopausal for at least 24
consecutive months) must agree to practice adequate contraception and to refrain from
breast-feeding, as specified in the informed consent.

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

Exclusion Criteria:

1. Patient has received preoperative chemotherapy and/or radiation.

2. Major cardiovascular or pulmonary comorbidity that precludes use of general
anesthesia.

3. Identification of metastatic disease.

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

5. Patients < 18 years of age.