A Pilot Phase I/II Study to Evaluate the Effects of Taxotere/Prednisone Plus Sunitinib in Chemotherapy-Naïve, Hormone Refractory Prostate Cancer Patients With Biochemical Relapse

Inclusion Criteria

Inclusion Criteria

- Subjects must have a histological diagnosis of adenocarcinoma of the prostate

- Age ≥ 18

- Subjects must have metastatic prostate cancer deemed to be unresponsive or refractory
to hormone therapy by one or more of the following (despite androgen deprivation and
anti-androgen withdrawal when applicable) check all that apply.

- Subjects may have received prior surgery. However, at least 21 days must have elapsed
since completion of surgery and Subject must have recovered from all side effects.

- Subjects must have adequate hepatic function as defined by:

- a serum bilirubin ≤1.5 x the institutional upper limit of normal (IULN),

- Serum glutamic-oxaloacetic transaminase (SGOT) or serum glutamic-pyruvic transaminase
(SGPT) ≤2.5 x the institutional upper limit of normal obtained within 14 days prior
to start of therapy

- Subjects must have 2 pre-study PSA > 2ng/ml at least 1 week apart within 28 days
prior to start of therapy

- Subjects must have been surgically or medically castrated. If method of castration is
luteinizing hormone-releasing hormone (LHRH) agonist (leuprolide or goserelin), then
the Subject should be willing to continue the use of LHRH agonists. Castration using
LHRH agonist should not be interrupted and subjects who have stopped treatment should
be willing to restart.

- Subjects must not take vitamins, herbs, or micronutrient supplement within 28 days
prior to start of therapy.

- Prior external beam radiation therapy (to less than 30% of the bone marrow only) is
allowed. This includes prior use of samarium, but subjects can not have received
prior strontium. At least 28 days must have elapsed since the completion of radiation
therapy and the Subject must have recovered from side effects. Soft tissue disease
which has been radiated in the prior 2 months is not assessable as measurable
disease.

- Subjects with a history of myocardial infarction are not eligible. Subjects must have
a baseline EKG to rule out underlying cardiac disease within 42 days prior to
registration. Subjects with a history of cardiac disease, specifically congestive
heart failure (CHF) are ineligible unless their disease is well-controlled. Subjects
with history of cardiovascular accident (CVA) or atrial fibrillation are ineligible.

- Subjects with a history of brain metastases or who currently have treated or
untreated brain metastases are not eligible. Subjects with clinical evidence of brain
metastases must have a brain CT or MRI negative for metastatic disease within 56 days
prior to registration.

*Liver function tests should be evaluated prior to each treatment.

- Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status
0-2.

- Subjects must have an adequate renal function as defined by:

- a serum creatinine ≤1.5 x the institutional upper limit of normal obtained within 14
days prior to start of therapy and a urine protein: creatinine (UPC) ratio of ≤ 1.0.

- Subjects must have the following hematological criteria (minimal values):

- Absolute neutrophil count ≥ 1,500/mm³

- Hemoglobin of ≥ 8.0gm/dL,

- White blood cell count ≥ 2500,

- Platelets ≥ 75,000/mm³

- Subjects must be able to take oral medications

Exclusion Criteria

- Subjects must not have received chemotherapy, biologic therapy or any other
investigational drug for any reason within 28 days prior to start of therapy and must
have recovered from toxicities of prior therapy to grade 1 or less with the exception
of alopecia.

- Subjects may not have ongoing problems with bowel obstruction or short bowel syndrome
characterized by grade 2 or greater diarrhea or malabsorptive disorders.

- Men of child bearing potential must be willing to consent to using effective
contraception while on treatment and for at least 3 months thereafter.

- Subjects with a history of severe hypersensitivity reaction to docetaxel or other
drugs formulated with polysorbate 80 will be excluded

- Subjects should not have psychological, familial, sociological, or geographical
conditions that do not permit medical follow-up or compliance with the study
protocol.

- Subjects should not have any medical life-threatening complications of their
malignancies

- Subjects should not have a known severe and/or uncontrolled concurrent medical
disease (e.g., uncontrolled diabetes, uncontrolled chronic renal or liver disease,
active uncontrolled infection, or HIV).

- Subjects should not have current, recent (within 4 weeks of the first infusion of
this study), or planned participation in an experimental drug study.

- Baseline blood pressure of < or equal to 150/100 mmHg. Subjects with a blood pressure
reading above this level should be initiated on anti-hypertensive therapy and may be
considered for protocol treatment when their blood pressure is adequately controlled.

- Subjects with New York Heart Association (NYHA) Grade II or greater congestive heart
failure are not eligible. Subjects must have a baseline multiple gated acquisition
scan (MUGA) or Echocardiogram with a calculated ejection fraction > or equal to 50%.

- Subjects with clinically significant peripheral vascular disease are not eligible.

- Subjects with evidence of bleeding diathesis or coagulopathy are not eligible.

- Subjects with central nervous system or brain metastases are not eligible.

- Subjects who had major surgical procedure, open biopsy, or significant traumatic
injury within 28 days prior to Day 0, anticipation of need for major surgical
procedure during the course of the study are not eligible.

- Subjects with minor surgical procedures, fine needle aspirations or core biopsies
within 7 days prior to Day 0 are not eligible.

- Subjects with history of abdominal fistula, gastrointestinal perforation, or
intra-abdominal abscess are not eligible.

- Subjects with serious, non-healing wound, ulcer, or bone fracture are not eligible.

- Subjects who are diagnosed of any other malignancy except non-melanomatous skin
cancer in the past 5 years are not eligible.

- Subjects receiving anticoagulation therapy (e.g. Coumadin) prior to registration are
not eligible. Subjects are permitted to have prior Coumadin for prophylaxis against
agents that might produce blood clots. Subjects with low dose Aspirin (86mg) are
acceptable.

- Subjects with active thrombophlebitis or hypercoagulability are not eligible.
Subjects with known history of pulmonary embolus are not eligible.

- All Subjects must be informed and must sign and give written informed consent in
accordance with institutional and federal guidelines. Subjects who are unable to
comply with study and/or follow-up procedures are not eligible.