Inclusion Criteria:- Patients must have histologically or cytologically confirmed adenocarcinoma of the pancreas. The site of the primary lesion should be confirmed endoscopically, radiologically, or surgically to be in the pancreas.

• Patients must be deemed unresectable due to involvement of critical vasculature, adjacent organ invasion, or presence of metastasis.
• Patients with a history of pancreatic adenocarcinoma treated by surgical resection who develop radiological or clinical evidence of metastatic cancer do not require separate histological or cytological confirmation of metastatic disease unless an interval of > 5 years has elapsed between the primary surgery and the development of metastatic disease. Clinicians should consider biopsy of lesions to establish diagnosis of metastatic pancreatic adenocarcinoma if there is substantial clinical ambiguity regarding the nature or source of apparent metastases.
• Patients must have a primary or metastatic lesion measurable in at least one dimension by Modified RECIST criteria (see Section 4.2) within 4 weeks prior to entry of study
• Patients must have WHO performance status of 0-2
• Patients must be >= 18 years of age
• Laboratory values <= 2 weeks prior to randomization:
• Absolute Neutrophil Count (ANC) >= 1.5 x 10^9/L (>= 1500/mm3)
• Platelets (PLT) >= 100 x 10^9/L (>=100,000/mm3)
• Hemoglobin (Hgb) >= 9 g/dL
• Serum creatinine <= 1.5 ULN
• Serum bilirubin <= 1.5 ULN
• Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) <= 3.0 x ULN (<= 5 x ULN if liver metastases present). Note: ERCP or percutaneous stenting may be used to normalize the liver function tests.
• Negative for proteinuria based on dip stick reading OR, if documentation of +1 result for protein on dip stick reading, then total urinary protein <= 500 mg and measured creatinine clearance (CrCl) >= 50 mL/min from a 24-hour urine collection
• Life expectancy >= 12 weeks
• Ability to give written informed consent according to local guidelines Exclusion Criteria:- For the phase I portion of the study, patients receiving prior gemcitabine will be excluded from enrollment. For the phase II portion of the study, patients receiving any prior chemotherapy (except for low-dose 5-fluorouracil as a radiosensitizer) will be excluded from enrollment. Patients must have recovered from all therapy-related toxicities.
• Prior full field radiotherapy <= 4 weeks or limited field radiotherapy <= 2 weeks prior to enrollment. Patients must have recovered from all therapy-related toxicities. The site of previous radiotherapy should have evidence of progressive disease if this is the only site of disease.
• Prior biologic or immunotherapy <= 2 weeks prior to registration. Patients must have recovered from all therapy-related toxicities
• Prior therapy with anti-VEGF agents
• History or presence of central nervous system (CNS) disease (i.e., primary brain tumor, malignant seizures, CNS metastases or carcinomatous meningitis)
• Patients with a history of another primary malignancy <= 5 years, with the exception of inactive basal or squamous cell carcinoma of the skin
• Major surgery (e.g. laparotomy) <= 4 weeks prior to enrollment. Minor surgery <= 2 weeks prior to enrollment. Insertion of a vascular access device is not considered major or minor surgery. Patients must have recovered from all surgery-related toxicities.
• Concurrent use of other investigational agents and patients who have received investigational drugs <= 4 weeks prior to enrollment.
• Female patients who are pregnant or breast feeding, or adults of reproductive potential not employing an effective method of birth control. Barrier contraceptives must be used throughout the trial in both sexes. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study. Women of childbearing potential must have a negative serum pregnancy test 48 hours prior to administration of study treatment. Please refer to appendix for a list of examples of substrates of human liver microsomal P450 enzymes
• Pre-existing peripheral sensory neuropathy with functional impairment >= CTCAE grade 2 neuropathy.
• Pleural effusion or ascites that causes respiratory compromise (>= CTCAE grade 2 dyspnea)
• QTc > 450 ms (male) or > 470 ms (female)
• Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:
• Uncontrolled high blood pressure, history of labile hypertension, or history of poor compliance with an antihypertensive regimen
• Unstable angina pectoris
• Symptomatic congestive heart failure
• Myocardial infarction <= 6 months prior to registration and/or randomization
• Serious uncontrolled cardiac arrhythmia
• Uncontrolled diabetes
• Active or uncontrolled infection
• Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
• Chronic renal disease
• Acute or chronic liver disease (e.g., hepatitis, cirrhosis)
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of PTK/ZK (i.e., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, bowel obstruction, or inability to swallow the tablets)
• Patients with confirmed diagnosis of human immunodeficiency virus (HIV) infection are excluded at the investigator's discretion if he/she feels that 1) a potential drug interaction between PTK/ZK and any of the patient's anti-HIV medications could influence the efficacy of the anti-HIV medication, or 2) it may place the patient at risk due to the pharmacologic activity of PTK/ZK. Please refer to appendix for a list of examples of substrates of human liver microsomal P450 enzymes
• Patients who are taking therapeutic warfarin sodium (Coumadin) or similar oral anticoagulants that are metabolized by the cytochrome P450 system. Heparin is allowed. Please refer to appendix for a list of examples of substrates of human liver microsomal P450 enzymes
• Patients unwilling to or unable to comply with the protocol