Study Combining Imatinib Mesylate (Gleevec) With Sorafenib in Patients With Androgen-independent Prostate Cancer (AIPC)
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Gleevec + Sorafenib
Intervention description: 400 mg Sorafenib every day (QD) 300mg Gleevec QD
Intervention MeSH terms: Sorafenib; Imatinib Mesylate
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: Male
Minimum age: 18 Years
Maximum age: 90 Years
Healthy volunteers: No
Keywords: AIPC, Prostate cancer; prostate

Summary:

      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.
    

Eligibility criteria:

        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.