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

- Echocardiogram or MUGA 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