Gemcitabine and Pazopanib in Metastatic Pancreatic Cancer

Inclusion Criteria:

* Patient must have a histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma.
* Patient must have metastatic disease that is not amenable to surgical resection.
* Patient must have measurable disease (by RECIST criteria), defined as at least one lesion that can be accurately measured in at least one dimension.
* Patient may have previously untreated disease or may have been previously treated if they meet the following criteria:

  * received adjuvant gemcitabine therapy \>6 months prior to enrollment with progression off therapy
  * received prior radiation therapy \> 4 weeks prior to study enrollment and have measurable tumor mass outside the radiation field
  * received prior radiation therapy \> 4 weeks prior to study enrollment, have a measurable tumor mass outside the radiation field, and received 5-FU as a radiation sensitizer \>4 weeks prior to study enrollment
* Patient must be \>=18 years old. Note: pazopanib is contraindicated in the pediatric population due to the potential effect on the epiphyseal growth plates.
* Patient must have an ECOG performance status of 0-1
* Patient must have normal organ and marrow function within 14 days of study initiation as defined below:

  * ANC ≥ 1.5 x 109/L
  * Hemoglobin ≥ 9 g/dL; patients may not have had a transfusion within 7 days of screening assessment
  * Platelets ≥ 100 x 109/L
  * PT or INR ≤ 1.2 x upper limit of normal (ULN)
  * PTT ≤ 1.2 x ULN
  * Total bilirubin ≤ 1.5 x ULN
  * AST and ALT ≤ 2.5 x ULN
  * Serum creatinine ≤ 1.5 mg/dL; if \> 1.5 mg/dL, calculated creatinine clearance must be ≥ 50 mL/min
  * Urine protein to creatinine ratio \< 1; if ≥ 1, then a 24-hour urine protein must be assessed and must be \< 1 g in order for patients to be eligible
* Patient must have the ability to understand and the willingness to sign a written informed consent document.
* Eligible patients of reproductive potential (both sexes) must agree to use adequate contraceptive methods.

Exclusion Criteria

* Patient has been treated with an agent that antagonizes the VEGF receptor.
* Patient has received any other investigational agents \< 28 days prior to enrollment.
* Patient has known brain metastases; these patients are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. In addition, patients with brain metastases may be at a higher theoretical risk for cerebral hemorrhage while taking pazopanib.
* Patient has a history of allergic reactions attributed to compounds of similar chemical or biologic composition to pazopanib, gemcitabine, or other agents used in the study.
* Patient has an increased risk of hemorrhage such as having received thrombolytic agents within the past month, being on an unstable dose of anticoagulation, or having a known bleeding diathesis.
* Patient has a clinically significant gastrointestinal abnormality that may increase the risk for GI bleeding such as:

  * Active inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease) or other gastrointestinal conditions with increased risk of perforation
  * History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess ≤ 28 days prior to beginning study treatment
* Patient has a history of any one or more of the following cardiovascular conditions within the past 6 months:

  * Cardiac angioplasty or stenting
  * Myocardial infarction
  * Unstable angina
  * Coronary artery by-pass graft surgery
  * Symptomatic peripheral vascular disease
  * Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
* Patient has prolonged QT intervals, taking antiarrhythmics or taking other medications that prolong QT
* Patient has poorly controlled hypertension (defined as systolic blood pressure (SBP) of ≥160 mmHg or diastolic blood pressure (DBP) of ≥ 90 mmHg). Note: initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry.
* Patient has a history of cerebrovascular accident, pulmonary embolism, or untreated deep venous thrombosis (DVT) within the past 6 months.
* Patient has had major surgery, trauma, non-healing wound, fracture, or ulcer within 28 days prior to first dose of gemcitabine and/or study drug (procedures such as catheter placement not considered to be major) OR minor surgery within 14 days prior to first dose of gemcitabine and/or study drug.
* Patient has significant proteinuria as evidenced by urine protein/creatinine ratio \>1
* Patient has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, cardiac arrhythmia, active second malignancy, or psychiatric illness/social situations that would limit compliance with study requirements.
* Patient is pregnant or breastfeeding. Pregnant women are excluded from this study because pre-clinical reproductive toxicity studies with pazopanib demonstrated reduced female fertility and teratogenic effects.
* Patient is known HIV-positive. These patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
* Patient is a known alcohol, cocaine, or IV drug abuser within 6 months prior to enrollment.
* Patient is receiving treatment with any of the following anti-cancer therapies:

  * Radiation therapy, surgery, or tumor embolization within 4 weeks prior to the first dose of pazopanib OR
  * Chemotherapy, immunotherapy, biologic therapy, investigational therapy, or hormonal therapy within 28 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib.
* Patient is experiencing any ongoing toxicity from prior anti-cancer therapy that is \> grade 1 and/or that is progressing in severity.
* Inclusion of Women and Minorities
* Both men and women and members of all races and ethnic groups are eligible for this trial.