Gemcitabine Hydrochloride With or Without Vismodegib in Treating Patients With Recurrent or Metastatic Pancreatic Cancer

Inclusion Criteria:

• Histologically or cytologically confirmed pancreatic adenocarcinoma meeting 1 of the following criteria:

  • Newly diagnosed, metastatic disease

  • Recurrent disease

    • Patients with recurrent disease after surgical resection must have sufficient archived tissue available for correlative studies
• 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
• No known brain metastases
• Karnofsky performance status 80-100%
• Life expectancy > 3 months
• Granulocytes ≥ 1,500/μL
• Platelet count ≥ 100,000/μL
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST/ALT ≤ 2.5 times ULN (≤ 5 times ULN in the presence of liver metastases)
• INR ≤ 1.5 (≤ 3 for patients on warfarin)
• Serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 65 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use at least one method of contraception for ≥ 4 weeks prior to, and then double-method of contraception during and for ≥ 12 months after completion of study treatment
• Able to swallow capsules
• No uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, or hypokalemia, defined as less than the lower limit of normal despite adequate electrolyte supplementation
• No malabsorption syndrome or other condition that would interfere with intestinal absorption
• No clinically active liver disease, including active viral or other hepatitis or cirrhosis

• No "currently active" second malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix

  • Patients are not considered to have a "currently active" malignancy if they have completed therapy and have no evidence of recurrence for ≥ 5 years

• No concurrent uncontrolled illness including, but not limited to, any of the following:

  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness or social situation that would limit compliance with study requirements
• No cerebrovascular accident within the past 6 months
• No recent myocardial infarction
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to hedgehog antagonist GDC-0449 or any other agents used in this study
• No blood donation for ≥ 12 months after completion of study treatment
• Other concurrent anticoagulants (including enoxaparin [Lovenox] and fondaparinux [Arixtra]) allowed
• No prior Hedgehog SMO inhibitor
• No prior chemotherapy for metastatic disease
• Prior adjuvant chemotherapy or adjuvant chemoradiotherapy allowed provided patient did not receive chemotherapy for metastatic disease AND adjuvant therapy was completed ≥ 6 months before the diagnosis of recurrent disease
• Prior surgery allowed provided patient did not receive adjuvant therapy AND surgery was completed ≥ 6 months prior to the diagnosis of recurrent disease
• No other concurrent investigational agents
• No other concurrent anticancer agents or therapies
• No concurrent ketoconazole or grapefruit juice
• No concurrent combination antiretroviral therapy for HIV-positive patients
• Concurrent warfarin allowed provided patient is on a stable therapeutic dose of warfarin, INR is in the target range (≤ 3), INR testing is performed weekly, and patient has no active bleeding or pathological condition that carries a high risk of bleeding