Treatment of Prostate Cancer With Adjuvant Bevacizumab Plus Erlotinib

This study explores the anti-tumor activity of adjuvant bevacizumab plus erlotinib in a
select group of prostate cancer patients deemed at high risk for early relapse following
radical prostatectomy.

Inclusion Criteria:

- Karnofsky performance status of > 80

- Patients must have localized, organ-confined prostate cancer documented by physical
examination, CT scan, or bone scan, and must have undergone radical prostatectomy.
Post RP must have documented node negative prostate cancer.

- Pretreatment granulocyte count > 1500/mm3, hemoglobin > 9.0 g/dL, and platelet count
> 100,000/mm3,

- Normal PT and PTT

- Serum creatinine < 2.0 mg/dL

- Adequate hepatic function with a serum bilirubin < upper limit of normal (ULN), AST
and ALT < 1.5x ULN, and alkaline phosphatase < 2.5x ULN.

- High-risk prostate cancer defined as a pre-RP prostate specific antigen level > 15
ng/dL or a Gleason score of > 8 or Stage T3 disease or positive surgical margins

- Men of childbearing potential must be willing to consent to using effective
contraception while on treatment and for 3 months thereafter

Exclusion Criteria:

- Evidence of small cell (neuroendocrine) tumor

- Evidence of metastatic disease

- Prior administration of immunotherapy, biological therapy, hormonal therapy or
radiation therapy for prostate cancer

- Active secondary malignancies (other than basal cell carcinoma of the skin)

- Serious, nonhealing wound, ulcer, or bone fracture.

- Clinically significant cardiovascular disease (e.g., blood pressure of >150/100 mmHg,
myocardial infarction, or unstable angina), New York Heart Association (NYHA) Grade
II or greater congestive heart failure, serious cardiac arrhythmia requiring
medication, or clinically significant peripheral vascular disease. Patients with a
history of myocardial infarction or stroke within the last 6 months will be excluded.

- Presence of seizures not controlled with standard medical therapy

- Active infection requiring parenteral antibiotics at the time of the first
administration of study drugs

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 0, or anticipation of need for major surgical procedure during the
course of the study; minor surgical procedures, fine needle aspirations or core
biopsies within 7 days prior to Day 0.

- Current, recent (within the 4 weeks preceding Day 0), or planned participation in
another experimental drug study

- Inability to comply with the study visit and follow-up schedule or procedures

- History of other disease, metabolic dysfunction, physical examination finding, or
clinical laboratory finding giving reasonable suspicion of a disease or condition
that contraindicates the use of an investigational drug or that might affect the
interpretation of the results of the study or render the subject at high risk from
treatment complications.

- Urine protein:creatinine ration > 1.0 at screening

- Evidence of bleeding diathesis or coagulopathy.

- History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess
within 28 days prior to Day 0.

- Presence of central nervous system or brain metastases