The purpose of this study is to determine the effectiveness of two drugs, docetaxel and Gleevec®(also called imatinib), in prostate cancer that no longer responds to hormone therapy. The investigators are interested in finding out if the combination of these two drugs is more effective than docetaxel alone in the treatment of prostate cancer.

This is a non-randomized multicenter Phase II trial of Gleevec and docetaxel in chemo naïve metastatic hormone refractory prostate cancer. The primary objective of this study is to assess the time to disease progression in patients with hormone refractory prostate cancer treated with daily oral imatinib and intravenous docetaxel, administered every three weeks. Secondary objectives include: 1) to assess the rate of response to imatinib and docetaxel, using Prostate Specific Antigen (PSA) and/or measurable disease; 2) to assess the overall survival of patients with hormone refractory prostate cancer treated with imatinib and docetaxel; and 3) to evaluate the qualitative and quantitative toxicities of this combination.

Inclusion Criteria:

1. Must have a histologic diagnosis of adenocarcinoma of the prostate Stage D2 that is unresponsive or refractory to hormone therapy. Must have metastatic prostate cancer with a rising PSA, and deemed to be hormone refractory.
2. All subjects must have pre-study PSA within 28 days prior to registration
3. Subjects who have measurable disease must have had X-rays, scans or physical examinations used for tumor measurement completed within 28 days prior to registration. Subjects must have non-measurable disease assessed within 28 days (for PSA level) or 42 days (for imaging studies) prior to registration.
4. Subjects with bone metastases, as documented by X-ray, bone scan, MRI, or biopsy.
5. All subjects must have had a CT scan of the abdomen and pelvis within 28 days prior to registration.
6. Subjects must have been surgically or medically castrated. If the method of castration was LHRH (Luteinizing Hormone-Releasing Hormone) agonists, then the subject must be willing to continue the use of LHRH agonists.
7. If the subject has been treated with non-steroidal anti-androgens or other hormonal treatment these agents must have been stopped at least 28 days prior to enrollment for flutamide or ketoconazole, and at least 42 days prior to enrollment for bicalutamide or nilutamide; and the subjects must have demonstrated progression of disease since the agents were suspended.
8. Prior radiation therapy is allowed. At least 21 days must have elapsed since the completion of radiation therapy, and the subject must have recovered from the side effects of the radiation
9. 9. Due to the unknown side effects of imatinib, men of reproductive potential must agree to use an effective contraceptive method.
10. Subjects must have recovered from major infections and/or surgical procedures and, in the opinion of the investigator, not have significant active concurrent other medical illness precluding protocol treatment.
11. ECOG performance status of 0-1
12. ANC ≥ 1,500/mL and a platelet count of ³ 100,000/mL. These tests must be obtained within 7 days prior to registration.
13. Serum bilirubin ≤ 1.3, SGOT and SGPT ≤ 2 x institutional upper limit of normal, and a serum creatinine ≤ 1.8 mg/dl. These tests must be obtained within 7 days prior to registration. Testosterone level may be done 28 days prior to study entry. Testosterone level should be below 50 ng/dL.

Exclusion Criteria:

1. No prior chemotherapy for hormone-refractory disease is allowed. At least three weeks must have elapsed since the completion of any non-cytotoxic investigational therapy, and the patient must have recovered from the side effects of the therapy.
2. No other cytotoxics, biological response modifiers, radiation therapy, corticosteroid or hormonal concomitant therapy (other than continuing LHRH treatment) may be given during protocol treatment. Bisphosphonates may be given during protocol treatment. No unconventional therapy may be given during protocol treatment.
3. Subjects must NOT have Grade III/IV cardiac problems as defined by the New York Heart Association Criteria.
4. Subjects with known chronic liver disease are NOT eligible
5. Must NOT have a known diagnosis of human immunodeficiency virus (HIV) infection.
6. Subjects must NOT have known brain metastases.
7. No prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ carcinoma of any site, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years.