Vismodegib and Gemcitabine Hydrochloride in Treating Patients With Advanced Pancreatic Cancer

Inclusion Criteria: * Patients must have histologically or cytologically confirmed pancreas cancer * Patients must have metastatic disease or recurrent disease following surgical therapy * Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan * Patients must have disease accessible for core needle biopsy both prior to initiation of therapy and on day 21 (+ or - 1 day) of GDC-0449 treatment * No previous systemic therapy for metastatic pancreas cancer is permitted; prior neoadjuvant or adjuvant therapy with chemotherapy and/or radiation is allowed provided that the last day of therapy was at least 6 months prior to registration * Life expectancy of greater than 12 weeks * Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%) * Leukocytes \>= 3,000/mcL * Absolute neutrophil count \>= 1,500/mcL * Platelets \>= 100,000/mcL * Total bilirubin =\< 2.0 mg/dl * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal; \< 5 x if liver involved in tumor * Creatinine \< 2.0 mg/dl * The effects of GDC-0449 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because hedgehog (Hh) signal pathway inhibitors as well as gemcitabine are known to be teratogenic, women of child-bearing potential and men must use two forms of contraception (i.e., barrier contraception and one other method of contraception) at least 4 weeks prior to study entry, for the duration of study participation, and for at least 12 months post-treatment; for appropriate methods of contraception considered acceptable; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; * Pregnancy testing: omen of childbearing potential are required to have a negative serum pregnancy test (with a sensitivity of at least 25 mIU/mL beta-human chorionic gonadotropin \[bHCG\]) within 10-14 days and within 24 hours prior to the first dose of GDC-0449 (serum or urine); a pregnancy test (serum or urine) will be administered every 4 weeks if their menstrual cycles are regular or every 2 weeks if their cycles are irregular while on study within the 24-hour period prior to the administration of GDC-0449; a positive urine test must be confirmed by a serum pregnancy test; prior to dispensing GDC-0449, the investigator must confirm and document the patient's use of two contraceptive methods, dates of negative pregnancy test, and confirm the patient's understanding of the teratogenic potential of GDC-0449 * Patients taking medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450) may be enrolled with caution; GDC-0449 is a substrate of CYP3A4; however, the in vitro metabolic conversion of GDC-0449 is low; effects of cytochrome (CYP) inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, St. John's wart, and troglitazone) on clinical concentrations of GDC-0449 are unknown; likewise, the effects of strong inhibitors of CYP3A4 (e.g., clarithromycin, erythromycin, itraconazole, ketoconazole, nefazodone, and telithromycin) on GDC-0449 clinical concentrations are unknown, and caution should be exercised when dosing GDC-0449 concurrently with inhibitors of CYP3A4; in addition, GDC-0449 inhibits CYP2C8, CYP2C9, and CYP2C19 drug metabolism enzymes in vitro at concentrations that may be clinically relevant; therefore, caution should be exercised when dosing GDC-0449 concurrently with medications that are substrates of CYP2C8, CYP2C9, and CYP2C19 and have narrow therapeutic windows * Ability to understand and willingness to provide written informed consent Exclusion Criteria: * Patients who have had chemotherapy or radiotherapy within 6 months prior to entering the study or those who have not recovered from adverse events due to agents administered more than 6 months earlier * Patients may not be receiving any other investigational agents * Patients with known brain metastases * History of allergic reactions attributed to compounds of similar chemical or biologic composition to GDC-0449 or other agents used in the study * Patients on anticoagulation with Coumadin are ineligible; however anticoagulation with enoxaparin is acceptable for study entry * Patients with malabsorption syndrome or other condition that would interfere with intestinal absorption; patients must be able to swallow capsules * Patients with clinically active liver disease, including active viral or other hepatitis or cirrhosis, are ineligible * Patients with uncontrolled hypomagnesemia or hypokalemia defined as less than the lower limit of normal for the institution, despite adequate electrolyte supplementation are excluded from this study * Patients with \> grade 1 hyponatremia or hypocalcemia are excluded from this study * 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 * Pregnant women are excluded from this study because GDC-0449 is a Hh pathway inhibiting agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with GDC-0449, breastfeeding should be discontinued if the mother is treated with GDC-0449; these potential risks may also apply to other agents used in this study * Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with GDC-0449; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated