Bevacizumab in Treating Patients With Relapsed Prostate Cancer That Did Not Respond to Hormone Therapy

PRIMARY OBJECTIVES:

I. The rate of prostate-specific antigen (PSA) response with avastin (bevacizumab) therapy in
androgen independent non-metastatic prostate cancer.

II. Toxicities associated with avastin therapy. III. Time to PSA progression.

SECONDARY OBJECTIVES:

I. Overall survival of androgen independent non-metastatic prostate cancer patients treated
with avastin.

II. The change in PSA velocity with avastin therapy in androgen-independent non-metastatic
prostate cancer.

III. Time to distant metastatic disease. IV. Circulating tumor cell count. V. Changes in
levels of N terminal collagen peptide and bone-specific alkaline phosphatase with avastin
therapy.

VI. Correlation of crosslinked N-telopeptide of type I collagen (NTX) and serum
B-Cell-Specific Activator Protein (BSAP) levels with time to PSA progression.

OUTLINE:

Patients receive bevacizumab intravenously (IV) over 30-90 minutes once every 14 days.
Courses repeat every 14 days in the absence of disease progression and unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Inclusion Criteria:

- A histologic diagnosis of prostate adenocarcinoma.

- No evidence of bone/visceral metastases as visualized on standard imaging such as bone
scan, chest X-ray, CT scan or MRI of abdomen and pelvis.

- PSA-only progression despite androgen deprivation therapy. PSA progression is defined
as 3 rising levels, with a minimum interval of 2 weeks between each determination. The
last determination must have a minimum value of

1ng/ml and be determined within two weeks prior to registration. If the second or
third confirmatory value is less than the previous value, the patient will still be
eligible if a repeat value (No. 4) is found to be greater than all the prior values.

- If patient has been on antiandrogen in the past 28 days, then PSA progression after
withdrawal period (28 days for flutamide and 42 days for bicalutamide or nilutamide)
is required.

- ECOG performance status of 0-1.

- No prior avastin therapy.

- No investigational or commercial agents or therapies (except LHRH agonists) may be
administered concurrently with the intent to treat the patient's malignancy. Patients
on LHRH agonists must continue the use of LHRH agonist therapy. Bisphosphonates can be
administered per treating physician discretion.

- At least 4 weeks must have elapsed since prior systemic therapy, except for LHRH
analogue therapy and steroids. If steroids are being used for therapy of prostate
cancer, these should be discontinued prior to starting avastin therapy.

- Age ≥ 18 years.

- Life expectancy of at least 6 months.

- Ability to understand and the willingness to sign a written informed consent that is
approved by the Institutional Human Investigation Committee.

- Use of effective means of contraception in subjects.

Exclusion Criteria:

Inability to comply with study and/or follow-up procedures.

- Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or
diastolic blood pressure > 100 mmHg on antihypertensive medications).

- Any prior history of hypertensive crisis or hypertensive encephalopathy.

- New York Heart Association (NYHA) Grade II or greater congestive heart failure (see
Appendix E).

- History of myocardial infarction or unstable angina within last 12 months prior to
study enrollment.

- History of stroke or transient ischemic attack within 6 months prior to study
enrollment.

- Known CNS disease.

- Significant vascular disease (e.g., aortic aneurysm, aortic dissection).

- Symptomatic peripheral vascular disease.

- Evidence of bleeding diathesis or coagulopathy.

- Patients on anticoagulants are allowed if patient has been on therapy for at least 4
weeks and patient has no acute thromboembolic activity.

- Major surgical procedure, open biopsy, or significant traumatic injury within. 28 days
prior to study enrollment or anticipation of need for major surgical procedure during
the course of the study.

- Core biopsy or other minor surgical procedure, excluding placement of a vascular
access device, within 7 days prior to study enrollment.

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
within 6 months prior to study enrollment.

- Serious, non-healing wound, ulcer, or bone fracture.

- Proteinuria at screening as demonstrated by:

1. Urine protein:creatinine (UPC) ratio ≥ 1.0 at screening

- Known hypersensitivity to any component of avastin.

- Refusal to use effective means of contraception.

- Patients with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse events.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to avastin.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Patients with immune deficiency such as HIV-positive patients or those receiving
combination anti-retroviral therapy are excluded from the study because of lack of
safety data for avastin in these patients.