A Phase II Study of Gemcitabine and Nab-Paclitaxel in Combination With GDC-0449 (Hedgehog Inhibitor) in Patients With Previously Untreated Metastatic Adenocarcinoma of the Pancreas

Inclusion Criteria:

1. Patient has histologically or cytologically confirmed metastatic adenocarcinoma of
the pancreas. Patients with islet cells tumors are excluded. Biopsy within 14 days of
starting treatment.

2. Patient has measurable disease, defined as at least one lesion that can be accurately
measured in at least one dimension (longest diameter to be recorded) as >20 mm with
conventional techniques or as >10 mm with spiral CT scan.

3. Patient has NOT received previous radiotherapy, surgery or chemotherapy or
investigational drug therapy for the treatment of metastatic disease. If the patient
received radiotherapy, chemotherapy or investigational therapy in the adjuvant
setting it should be completed 3 weeks prior to enrollment. If a patient received
gemcitabine in the adjuvant setting, tumor recurrence must have occurred at least
six months after completing the last dose of gemcitabine

4. Age >18 years.

5. Life expectancy of greater than 1 month.

6. ECOG performance status 0 or 1 (Karnofsky >70%).

7. Patients must have adequate organ and marrow function

Exclusion Criteria:

1. Patient had received chemotherapy or radiotherapy for metastatic disease

2. Patient is receiving other investigational agents.

3. Patient has known brain metastases, unless previously treated and well controlled
for at least three months (defined as clinically stable, no edema, no steroids and
stable in 2 scans at least 4 weeks apart)

4. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to GDC-0449 or other agents used in the study.

5. Patients taking medications with narrow therapeutic indices that are metabolized by
cytochrome P450 (CYP450), including warfarin sodium (Coumadin®) are ineligible.

6. Uncontrolled illness including, but not limited to, ongoing or active infection
requiring IV antibiotics, symptomatic congestive heart failure not controlled with
medication, unstable angina pectoris, cardiac arrhythmia, or psychiatric
illness/social situations that would limit compliance with study requirements.

7. Pregnant women are excluded

8. Patient has undergone a major surgery, other than diagnostic surgery (i.e. surgery
done to obtain a biopsy for diagnosis without removal of an organ) within four weeks
prior to Day 1 of treatment on this study.

9. History of other disease, metabolic dysfunction, physical examination finding, or
clinical laboratory finding giving reasonable suspicion of a disease or condition
that contraindicates use of an investigational drug or that might affect
interpretation of the results of the study or render the patient at high risk from
treatment complications