Inclusion Criteria:

- Histologically or cytologically confirmed gastric or gastroesophageal junction (GEJ)
adenocarcinoma not amenable to surgical resection

- Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1
dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques
or as ≥ 10 mm with spiral CT scan

- Must be willing to provide blood and tissue samples for research purposes

- No known brain metastases

- ECOG performance status (PS) 0-1 or Karnofsky PS 70-100%

- Life expectancy > 3 months

- Absolute neutrophil count ≥ 1,500/mcL

- Platelets ≥ 100,000/mcL

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST and ALT ≤ 2.5 times ULN (≤ 5.0 times ULN in the presence of liver metastases)

- Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use 2 forms of effective contraception (i.e., barrier
contraception and one other method of contraception) for ≥ 4 weeks before, during,
and ≥ 12 months after completion of study treatment

- Must agree to placement of a central venous catheter for chemotherapy administration

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to hedgehog antagonist GDC-0449, fluorouracil, or oxaliplatin

- No malabsorption syndrome or other condition that would interfere with intestinal
absorption

- Able to swallow whole capsules

- No clinically active liver disease, including viral or other hepatitis or cirrhosis

- No uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, or hypokalemia defined as
less than the lower limit of normal for the institution, despite adequate electrolyte
supplementation

- No pre-existing peripheral sensory neuropathy > grade 1

- No previous or other concurrent malignancy, except treated basal cell or squamous
cell skin cancer, in situ cervical cancer, lobular carcinoma in situ in one breast,
or other cancer from which the patient has been disease-free ≥ 5 years

- No uncontrolled intercurrent illness, including, but not limited to, ongoing or
active infection, symptomatic congestive heart failure, unstable angina pectoris,
cardiac arrhythmia, or psychiatric illness/social situations that would limit
compliance with study requirements

- Medications with narrow therapeutic indices that are metabolized by cytochrome P450
(CYP450), including warfarin sodium (coumadin) are allowed as long as on a stable
therapeutic dose

- More than 6 months since prior adjuvant chemotherapy or chemoradiation

- No prior chemotherapy for advanced disease

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No other concurrent investigational agents