A Study of Vismodegib in Men With Metastatic CRPC With Accessible Metastatic Lesions for Tumor Biopsy

Inclusion Criteria: * Men with metastatic castration-resistant prostate cancer (mCRPC), with accessible metastatic soft-tissue lesions for tumor biopsy * Greater than 18 years of age * Evidence of disease progression (PSA progression, or radiographic/clinical progression \[PCWG2\]) * PSA progression is defined as at least two consecutive rises in serum PSA, obtained at a minimum of 1-week intervals, and each value ≥ 2.0 ng/mL. * Radiographic progression is defined for soft tissue lesions using RECIST criteria, i.e. an increase greater than 20% in the sum of the longest diameter of all target lesions based on the smallest sum longest diameter since treatment started or the appearance of one of more new lesions with a confirmatory scan 6 or more weeks later. Radiographic progression will be defined for bone lesions as the appearance of two new lesions with a confirmatory scan performed 6 or more weeks later that shows at least 2 or more additional new lesions. * Presence of ≥1 metastatic site (nodal, visceral) that is amenable to core biopsy * Castrate serum testosterone (\<50 ng/dL) * Prior anti-androgens are permitted but not required (2 week washout from anti-androgens) * Prior abiraterone and enzalutamide are permitted (2 week washout for both agents) * Prior immunotherapy (e.g. sipuleucel-T), and chemotherapy are permitted (4 week washout period from chemotherapy) * Bisphosphonates and denosumab are permitted, if on a stable dose for ≥4 weeks * Life expectancy ≥12 months * Adequate renal, liver, and bone marrow function with the following acceptable initial laboratory values: * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be ≤ 2.5 x the upper limit of normal (ULN). * Total bilirubin must be ≤ 1.5 x ULN. * Estimated creatinine clearance using the Cockcroft-Gault formula must be \> 40 mL/minute (See section 12.2 for formula) * Absolute neutrophil count (ANC) must be ≥ 1500/μL * Platelet count must be ≥ 100,000/μL * Willing and able to provide written informed consent and HIPAA authorization for the release of personal health information. NOTE: HIPAA authorization may be either included in the informed consent or obtained separately. * Karnofsky Performance status/ECOG Performance Status ≥70/2 (Appendix A: Performance Status Criteria) * Male patients must use condoms at all times, even after a vasectomy, during sexual intercourse with female partners of reproductive potential during treatment with vismodegib and for 2 months after the last dose to avoid exposing a pregnant partner and unborn fetus to vismodegib. Exclusion Criteria: * Current use of systemic corticosteroids (\>5 mg prednisone) * Known brain metastases, or untreated meningeal/dural disease * Receiving any other investigational agents or receipt of another investigational agent within 4 weeks of study entry * Patients taking anticoagulants or with a history of a bleeding diathesis (due to need for visceral biopsy) * Use of any prohibited concomitant medications (washout period of 1 week) * Insufficient time from last prior regimen or radiation exposure (washout period of 4 weeks) * Grade \> 2 treatment-related toxicity from prior therapy * Any other condition which, in the opinion of the Investigator, would preclude participation in this trial