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 abitererone, 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 adn 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 - Echocardiogram demonstrating ejection fraction within institutional normal limits Exclusion Criteria: - No previous therapy with lapatinib - No previous therapy with ketoconazole within 3 months of starting trial - The use of complementary therapy directed at prostate cancer treatment excluding the following: green tea, commercial multivitamin preparations. Vitamin B complex, C, D, E and multivitamins are permitted if these are being taken at less than 3 times the RDA - The concomitant use of drugs known to be narrow therapeutic index CYP3A4 substrates are excluded - Drugs that are sensitive to CYP3A4 substrates are excluded - Patients taking drugs that may further prolong QT intervals and present a known risk for Torsades de Pointes are excluded. - Patients who have alcohol or drug dependence currently or in the last 6 months are excluded from this study - Any other events, other than those defined above, in the opinion of the investigator, may make the patient ineligible for this trial - No contraindication to biopsy such as bleeding disorders. Patients on anticoagulants such as warfarin must be able to safely stop the drug for a three-day period. Patients may not go on heparin during this time - No active malignancy other than skin cancer or superficial bladder cancer - Cardiac disease: congestive heart failure > class II NYHA. Patients must no have unstable angina or new onset angina or myocardial infarction within the past 6 months. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy. Patients must have an ejection fraction within normal limits at the enrolling institution based on an echocardiogram - Uncontrolled hypertension defined as sustained BP > 160 and diastolic > 100 despite optimal medical management - Known HIV or chronic Hep B or C - Thrombolic or embolic events such as CVA within the last 6 months - Pulmonary hemorrhage or any bleeding event CTCAE Grade 2 or greater within 6 months of first dose of study drug of KHAD - Serious non-healing wound, ulcer, or bone fracture - Evidence of history of bleeding diathesis or coagulopathy - Major surgery or significant traumatic injury within 4 weeks of first study drug of KHAD