Eligible patients will be enrolled in one of 4 cohorts where each cohort will allow 3 patients to be on study. Patients will receive both study drugs on escalated dosing schedule until the maximum of 400 mg PO BID is reached for both drugs or toxicity is established. Once the pre-specified 400 mg by mouth two times a day (PO BID) dosing for both drugs is reached without toxicity, the study will close for accrual. If toxicity is noted prior to reaching the 400 mg PO BID dosing, then the dosing schedule that is deemed safest as per study design will be the one used for any future phase II study.

Gleevec and Sorafenib have modest efficacy in androgen-independent prostate cancer (AIPC) and the fact that both agents can be given orally with what appears to be tolerable side effects, we hypothesize that combining both agents may provide patients with another effective regimen in a disease where therapeutic options are limited. This study is designed to investigate the safety of combining Gleevec and Sorafenib as well as feasibility in AIPC patients who have failed one or more lines of systemic chemotherapy. Once safety is established, a follow-up phase II study will commence to investigate efficacy.

Inclusion Criteria:

1. Patients 18 years of age or older.

2. Histologically documented diagnosis of Prostate Cancer regardless of Gleason score.

3. Androgen-Independent Prostate Cancer

4. At least one measurable site of disease

5. Patients must have failed one or more lines of systemic chemotherapy, regardless of the chemotherapeutic agent used. There is NO limit to how many lines of chemotherapy a patient can receive

6. Patients receiving anti-coagulation treatment with an agent such as heparin may be allowed to participate. Patients on Warfarin are NOT allowed to participate.

7. Last chemotherapy exposure 4 weeks prior to study entry

8. Prior exposure to Sorafenib is allowed as long as last Sorafenib dose was 3 weeks or more from study entry

9. Prior exposure to Gleevec is an EXCLUSION

10. Progression after chemotherapy can be demonstrated radiographically (as per Response Evaluation Criteria in Solid Tumors (RECIST) criteria) or biochemically with prostate-specific antigen (PSA) being elevated more than 25% than previous value as long as a repeat PSA confirms progression. (repeat PSA should be done within 3 weeks from the last one). Patients with bone-only disease are considered progressing if there are two more lesions on a new bone scan.

11. Performance status 0,1, 2 (ECOG)

12. Adequate end organ function, defined as the following:

    • total bilirubin < 1.5 x Upper Limit of Normal (ULN), serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) < 2.5 x Upper Limit of Normal (UNL), creatinine < 1.5 x Upper Limit of Normal (ULN), absolute neutrophil count (ANC) > 1.0 x 109/L, platelets > 75 x 109/L.

13. Men of childbearing potential must agree to employ an effective barrier method of birth control prior to the study entry, throughout the duration of the study and for up to 3 months following discontinuation of study drug.

14. Written, voluntary informed consent.

15. Patients are allowed the following concurrent therapies:

    • Intravenous bisphosphonates if administered for bone metastases
    • luteinizing hormone releasing hormone (LHRH) analogues
    • Narcotic-type medical interventions to control malignancy-related pain

Exclusion Criteria:

1. Patient has received any other investigational agents within 21 days of first day of study drug dosing, unless the disease is rapidly progressing.
2. Patient is < 3 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal or squamous cell skin cancer. Existence of any other malignant disease is not allowed.
3. Patient with Grade III/IV cardiac problems
4. Patient has a severe and/or uncontrolled medical disease
5. Patient has a known brain metastasis.
6. Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
7. Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
8. Pulmonary hemorrhage/bleeding event > Common Toxicity Criteria for Adverse Effects (CTCAE) Grade 2 within 4 weeks of first dose of study drug.
9. Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug.
10. Serious non-healing wound, ulcer, or bone fracture.
11. Use of St. John's Wort or rifampin (rifampicin).
12. Any condition that impairs patient's ability to swallow whole pills.
13. Patient has known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis).
14. Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
15. Patient previously received radiotherapy to ³ 25 % of the bone marrow
16. Patient had a major surgery within 2 weeks prior to study entry.
17. Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.