First-Line Gemcitabine Chemotherapy With Our Without Sunitinib In Advanced or Metastatic Pancreatic Cancer

Prospective Randomized Phase II Trial With Gemcitabine Plus Sunitinib Versus Gemcitabine Alone in First-line Therapy of Metastatic or Locally Advanced Pancreatic Cancer

Primary objective: to evaluate whether the addition of sunitinib prolongates the Progression-Free Survival (PFS) in patients with advanced pancreatic cancer receiving first-line gemcitabine chemotherapy.

Inclusion Criteria:

• Patients who suffer from locally advanced or metastatic pancreatic cancer
• Patients with measurable disease (at least one uni-dimensionally measurable target lesion by CT-scan or MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST).
• ECOG performance status 0 to 1
• Signed written informed consent.
• White blood cell count (WBC) >= 3x10^9/L with neutrophils >= 1.5 x 10^9/L, platelet count >= 100x10^9/L, hemoglobin >= 5.6 mmol/L (9 g/dL).
• Total bilirubin < 2 x upper limit of normal.
• AST and ALT < 2.5 x upper limit of normal, or < 5 x upper limit of normal in case of liver metastases.
• Serum creatinine < 1.5 x upper limit of normal
• Normal ECG without QT prolongation

Exclusion Criteria:

• Resectable pancreatic cancer
• Previous chemotherapy (for adjuvant or metastatic disease)
• Any investigational drug within the 30 days before inclusion.
• Prior use of sunitinib or other multitarget tyrosine kinase inhibitor
• Pregnancy (absence to be confirmed by beta-hCG test) or lactation period.
• Men or women of child-bearing potential who are sexually active and unwilling to use a medically acceptable method of contraception during the trial.
• Clinically symptomatic brain or meningeal metastasis. (known or suspected)
• Cardiac arrhythmias requiring anti-arrhythmics (excluding beta blockers or digoxin).
• History of any of the following cardiac events within the past 6 months: myocardial infarction (including severe/unstable angina; coronary/peripheral artery bypass graft; symptomatic congestive heart failure (CHF) > NYHA Class II; cerebrovascular accident or transient ischemic attack; pulmonary embolism
• Uncontrolled severe hypertension (failure of diastolic blood pressure to fall below 90 mm Hg despite the use of up to 3 anti-hypertensive drugs
• Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease or chronic diarrhea
• Previous malignancy (other than pancreatic cancer) in the last 5 years except basal cell cancer of the skin, pre-invasive cancer of the cervix or superficial bladder tumor [Ta, Tis and T1].
• History of organ allograft
• Patients requiring long-term cortisone therapy
• Patients requiring oral anticoagulation treatment (such as marcoumar)