To determine the response rate and survival of gemcitabine and pazopanib in patients with
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. See Section 10 for
the evaluation of measurable disease.
- 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.
