Ketoconazole, Hydrocortisone, Dutasteride and Lapatinib (KHAD-L) in Prostate Cancer

Inclusion Criteria: * Patients with CRPC with metastatic bone disease. At least one site of metastatic disease must be amenable to a needle biopsy. Bone sites include lumbar vertebrae, pelvic bones and long bones. Excluded sites are thoracic, cervical vertebrae, skull and rib lesions * Patients may have had a number of previous hormonal therapies including ketoconazole and abiraterone, provided these were discontinued \>3 months before starting the trial * Patients may have had any number of previous cytotoxic therapies * Castrate resistant disease as defined by PSA working group. Patients must have a rise in PSA on two successive determinations at least one week apart and PSA levels 5ng/ml or greater and testosterone levels \<50 * Adequate renal, hepatic and bone marrow function as outlined in protocol * PTT\< 60, INR \<1.5NL unless on warfarin therapy * \> 6 month life expectancy * At least a 4 week interval from previous treatment other than LHRH analog and bisphosphonates. Patients on bicalutamide must have discontinued this medication for at least 6 weeks to be eligible * Patients receiving bisphosphonate can be maintained on this therapy * No major surgery or radiation therapy within 4 weeks * No strontium-89 or samarium-153 therapy within 4 weeks * ECG showing normal QT interval * No thromboembolism in past 6 months * Age \> 18 years * Investigator must check current patient medications against the list of CYP3A4 inhibitors and inducers prior to registration * Echocar…