Multimodality Therapy for Recurrent High Risk Prostate Cancer: A Phase II Study

Inclusion Criteria:

1. Prostate adenocarcinoma with evidence of recurrent disease as measured only by rising
PSA, without evidence of metastatic disease by bone scan or CT scan within 4 weeks of
entry

2. PSA ≤ 3.0 ng/ml and ≥ 0.1 ng/ml within 2 weeks of registration

3. Radical prostatectomy within 4 years of registration.

4. Rising PSA as defined by 1 or more PSA values greater than the nadir value after
radical prostatectomy, separated by at least 4 weeks.

5. Gleason sum at radical prostatectomy of 7-10 (4+3 or 3+4 allowed)

6. Informed consent

7. Age > 18 years.

8. Adequate laboratory parameters:

- leukocytes ≥ 3,000/uL

- absolute neutrophil count ≥ 1,500/uL

- platelets ≥ 75,000/uL

- hemoglobin > 9.0 g/dl

- total bilirubin within normal institutional limit

- AST(SGOT)/ALT(SGPT) < 2.5x institutional upper limit

- creatinine < 2.0x institutional upper limit

9. Karnofsky Performance Status ≥ 80 (Attachment 2).

10. Written, signed, dated, and witnessed IRB approved informed consent form (ICF) before
any screening procedures are performed.

11. Peripheral neuropathy ≤ grade 1

Exclusion Criteria:

1. Evidence of metastatic disease by CT scan, physical exam, or bone scan within 4 weeks
of registration

2. History of bleeding disorders or medical comorbidities that in the opinion of the
investigator would preclude the use of systemic chemotherapy

3. Prior systemic or biologic therapy, including pre-operative therapies or adjuvant
chemotherapy, biologic therapy, or hormonal therapy

4. Life expectancy of less than 5 years from medical co-morbidities by physician
judgment

5. Non-adenocarcinoma prostate cancer pathology at radical prostatectomy

6. Prior radiotherapy to the abdomen or pelvis

7. Less than or equal to 6 weeks from prior major surgery, including radical
prostatectomy, open biopsy, or traumatic injury.

8. Recent cardiovascular event (within 12 months) including unstable angina, myocardial
infarction, severe or at rest claudication, or stroke/CVA.

9. Subjects receiving known strong CYP3A4 isoenzyme inhibitors and/or inducers. Subjects
on acceptable CYP3A4 isoenzyme inhibitors and/or inducers are eligible, provided they
have been taking a stable regimen for at least 4 weeks prior to screening.

10. Presence of a non-healing wound or ulcer.

11. Grade >= 3 hemorrhage within the past month.

12. Hypertension with systolic blood pressure of >140 mm Hg and/or diastolic pressure >90
mm Hg at the time of screening. Anti-hypertensive medications are permitted.

13. Subjects with American Heart Association (AHA) Class 2-4 heart disease or any history
of congestive heart failure with an ejection fraction <50%.

14. Subjects with inability to tolerate or absorb oral medications.

15. QTc interval >480 msec on baseline EKG. Subjects may not be taking a medication
known to significantly prolong the QTc interval.

16. Subjects who have not recovered from prior biopsy, surgery, traumatic injury, and/or
radiation therapy.

17. Anticoagulation with warfarin (therapeutic doses of warfarin for catheter patency are
permitted). Low molecular weight heparin is permitted.

18. Active infection(s), active antimicrobial therapy or serious intercurrent illness.

19. Any other major medical or psychiatric illness that, in the investigator's judgment,
will substantially increase the risk associated with the subject's participation in
this study, including inability to absorb oral medications.