A Randomized Phase III Trial Of Gemcitabine Plus Bevacizumab (NSC#704865 IND#7621) Versus Gemcitabine Plus Placebo In Patients With Advanced Pancreatic Cancer

Inclusion Criteria:

- Histologic or cytologic documentation of adenocarcinoma of the pancreas;
documentation of disease extent by CT scan is required; radiologically measurable
disease is not required; patients with documented invasion of adjacent organs (e.g.,
duodenum, stomach) by CT scan are not eligible

- No prior chemotherapy for metastatic disease

- If the patient received adjuvant therapy, it must have been completed at least 4
weeks prior to enrollment on this study; the patient must have recovered from all
treatment related toxicities and must have evidence of disease progression following
adjuvant treatment

- Prior radiation therapy, with or without a radiosensitizing dose of
fluoropyrimidines, is allowed provided the patient has disease outside of the
radiation port; at least 4 weeks must have elapsed from completion of the radiation
therapy and all signs of toxicity must have resolved

- No prior treatment with gemcitabine or bevacizumab in the adjuvant or metastatic
setting

- No current or recent (within 1 month) use of a thrombolytic agent

- Patients may not have had prior therapy with other VEGF inhibitors

- No recent invasive surgical procedures; this includes:

- Major surgical procedure (e.g. exploratory laparotomy or laparoscopy), open
biopsy, or significant traumatic injury within 28 days prior to registration

- Fine needle aspirations or venous access device within 7 days prior to
registration

- Anticipation of need for major surgical procedures during the course of the
study

- No clinically significant cardiovascular disease; this includes:

- Uncontrolled hypertension (blood pressure > 150/90 on medication)

- New York Heart Association grade II or greater congestive heart failure

- Serious cardiac arrhythmia requiring medication

- No recent (within 6 months) arterial thrombotic events, including transient ischemic
attack (TIA), cerebrovascular accident (CVA), unstable angina, or myocardial
infarction (MI); patients with clinically significant peripheral artery disease
(i.e., claudication on less than one block) are also ineligible

- No evidence of CNS disease, including primary brain tumor, or any brain metastasis

- No serious or non-healing wound, ulcer or bone fracture

- No serious active infection (viral, fungal bacterial); no infection requiring
parenteral antibiotics at time of registration

- Patients with known hypersensitivity of Chinese hamster ovary cell products or other
recombinant human antibodies are not eligible

- Patients with a "currently active" second malignancy other than non-melanoma skin
cancers are not to be registered; patients are not considered to have a "currently
active" malignancy if they have completed therapy and considered by their physician
to be at less than 30% risk of relapse

- Women must be non-pregnant and non-breast feeding

- ECOG Performance status of 0, 1 or 2

- Granulocytes ≥ 1,500/μl

- Platelet count ≥ 100,000/μl

- Creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 60 mL/min

- Total bilirubin ≤ 1 x upper limit of normal

- SGOT(AST) ≤ 2.5 x upper limit of normal

- PT INR =< 1.5, unless patient is on full dose warfarin

- Urine protein; for ≥ 1+ proteinuria, 24 hour urine collection must demonstrate < 1 gm
of protein/24 hours

- Required diagnostic procedures:

- CT of the abdomen

- Chest x-ray