A Phase II Study of BAY 43-9006/Gemcitabine for Advanced Pancreatic Cancer

Inclusion Criteria:

- Histologically or cytologically confirmed adenocarcinoma of the pancreas

- Locally advanced or metastatic disease

- Locally advanced disease must extend outside the boundaries of a standard
radiotherapy port

- Not amenable to curative surgery or radiotherapy

- Measurable disease

- At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional
techniques OR ≥ 10 mm by spiral CT scan

- Pleural effusion and ascites are not considered measurable lesions

- Outside prior radiotherapy port

- No known brain metastases

- Performance status - ECOG 0-1

- Performance status - Karnofsky 70-100%

- More than 3 months

- WBC ≥ 3,000/mm^3

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- No evidence of bleeding diathesis

- Bilirubin normal

- AST and/or ALT ≤ 2.5 times upper limit of normal

- Creatinine normal

- Creatinine clearance ≥ 60 mL/min

- No uncontrolled hypertension

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No active or ongoing infection

- No other active malignancy

- No history of allergic reaction attributed to compounds of similar chemical or
biological composition to sorafenib or other study agents

- No psychiatric illness or social situation that would preclude study compliance

- No other uncontrolled illness

- No prior antiangiogenic agents

- No prior cytotoxic chemotherapy for metastatic disease

- At least 4 weeks since prior adjuvant chemotherapy (6 weeks for nitrosoureas or
mitomycin) and recovered

- No prior gemcitabine

- See Disease Characteristics

- At least 4 weeks since prior radiotherapy and recovered

- No prior investigational drugs

- No prior sorafenib

- No prior MAPK signaling agents

- Concurrent warfarin anticoagulation allowed provided the following criteria are met:

- Therapeutic on a stable warfarin dose

- INR ≤ 3

- Undergo weekly INR testing

- No active bleeding or pathological condition that carries a high risk of
bleeding

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No other concurrent investigational agents

- No other concurrent anticancer therapies