Adjuvant Intraperitoneal Gemcitabine for Resectable Pancreatic Adenocarcinoma
Adjuvant Intraperitoneal Gemcitabine for Resectable Pancreatic Adenocarcinoma
This is a phase II study evaluating the use of intraperitoneal gemcitabine given
 intraoperatively and as adjuvant therapy for patients with resectable pancreas cancer.

 The primary objective of this study is to evaluate the overall safety of intraperitoneal
 gemcitabine given intraoperatively and postoperatively for adjuvant treatment of resectable
 pancreatic adenocarcinoma.

 The secondary objectives are to evaluate the efficacy of this treatment regimen as reflected
 in overall survival at 2-years, to study the patterns of disease recurrence following this
 treatment, to study the pharmacology of intraperitoneal gemcitabine and to study changes in
 peritoneal cytology with pancreatic cancer resection.
Inclusion Criteria:

 -  Patients must have histologically or cytologically confirmed adenocarcinoma of the
 pancreas or periampullary cancer (duodenum, ampulla of Vater or distal common bile
 duct).

 -  Patients without a histologically confirmed diagnosis prior to surgical exploration,
 will have intraoperative frozen section to confirm the diagnosis prior to the
 administration of intraoperative intraperitoneal gemcitabine.

 -  Patients must undergo adequate preoperative imaging evaluation to determine
 resectability including contrast enhanced CT scan or MRI with or without endoscopic
 ultrasound

 -  Patients must have a complete surgical resection to grossly negative margins. The
 margins will be assessed in a routine fashion: the surgeon will decide on the level of
 transection based on visual inspection making sure that the visible/palpable tumor is
 removed with a negative margin. The specimen will be assessed for pancreatic duct and
 bile duct margin by intraoperative frozen section and an attempt will be made to have
 microscopically negative margins in all cases.

 -  Patients who have not received chemotherapy for the treatment of their pancreatic
 cancer prior to surgery scheduled at the Washington Hospital Center may be included in
 the protocol.

 -  Age >18 years. Because no dosing or adverse event data are currently available on the
 use of gemcitabine in patients <18 years of age, children are excluded from this study
 but will be eligible for future pediatric phase 2 combination trials.

 -  Life expectancy of greater than 6 months

 -  ECOG (Eastern Cooperative Oncology Group) performance status <2

 -  Patients must have normal organ and marrow function as defined below:

 -  leukocytes >3,000/mcL

 -  absolute neutrophil count >1,500/mcL

 -  platelets >100,000/mcL

 -  total bilirubin within normal institutional limits or compatible with preoperative
 biliary obstruction caused by the tumor

 -  AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal or compatible with
 preoperative biliary obstruction caused by the tumor

 -  creatinine within normal institutional limits OR

 -  creatinine clearance >45 mL/min

 -  The effects of gemcitabine on the developing human fetus at the recommended
 therapeutic dose are unknown. For this reason, women of child-bearing potential and
 men must agree to avoid pregnancy prior to study entry and for the duration of study
 participation. Should a woman become pregnant or suspect she is pregnant while
 participating in this study, she should inform her treating physician immediately.

 -  Ability to understand and the willingness to sign a written informed consent document.

 Exclusion Criteria:

 -  Patients who have had radiotherapy or chemotherapy for their pancreatic cancer

 -  Patients receiving any other investigational agents.

 -  Patients with metastatic disease in the liver or other distant sites, intraabdominal
 lymph nodes beyond regional draining lymph nodes or with malignant ascites

 -  History of allergic reactions attributed to compounds of similar chemical or biologic
 composition to gemcitabine.

 -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
 infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
 arrhythmia, or psychiatric illness/social situations that would limit compliance with
 study requirements.

 -  Pregnant women are excluded from this study because gemcitabine is an antimetabolite
 (pyrimidine analog) with the potential for teratogenic or abortifacient effects.
 Because there is an unknown but potential risk for adverse events in nursing infants
 secondary to treatment of the mother with gemcitabine, breastfeeding should be
 discontinued if the mother is treated with gemcitabine. These potential risks may also
 apply to other agents used in this study.

 -  HIV-positive patients on combination antiretroviral therapy are ineligible because of
 the potential for pharmacokinetic interactions with gemcitabine. In addition, these
 patients are at increased risk of lethal infections when treated with
 marrow-suppressive therapy. Appropriate studies will be undertaken in patients
 receiving combination antiretroviral therapy when indicated.