Docetaxel, Bevacizumab and Androgen Deprivation Therapy for BCR After Definitive Local Therapy for Prostate Cancer

A single arm phase 2 study designed to evaluate the rate of patients free from PSA
progression (TTP) one year after completing ADT for men with BCR after definitive local
therapy for prostate cancer.

The null and alternative TTP rate were 41% and 60% respectively. A sample size of 42 would
provide 80% power to detect the difference with a 2-sided type I error rate of 0.05.'

The primary objective was to evaluate the proportion of patients free from PSA progression
after completing one year of ADT

The secondary objectives included

1. PSA response (< 0.2 ng/mL and < 0.01) at completion of docetaxel/bevacizumab, at
completion of ADT and one year off ADT

2. Correlation of PSA response and TTP

3. Toxicity

4. Testosterone recovery at 6, 12 months off ADT

Treatment schedule details are as follows:

- Each treatment cycle lasts three weeks. During the first three months, participants
will receive the Avastin and docetaxel on day 1 of each three-week cycle for a total of
four doses of docetaxel/Avastin. Avastin and docetaxel are administered intravenously.
The Avastin will continue to be given every three weeks after the docetaxel is
completed for a total of 17 doses (one year) of Avastin therapy.

- Participants will receive zoladex (or lupron) on day 1 of the first cycle and then
every 3 months for a total of 18 months. Zoladex is administered subcutaneously and
Lupron is administered intramuscularly.

- Bicalutamide pills will be started at the completion of docetaxel chemotherapy (start
of month 4) and will be taken once daily until hormone therapy is completed (total of
15 months).

- During all treatment cycles, the participant will have a physical exam and will be
asked questions about their general health and specific questions about any problems
they might be experiencing. Blood work will be performed every three weeks for the
first three months and then every three months while on hormone therapy and during
follow-up.

- After the final treatment participants will have a follow-up visit every three months
for the first two years, every 4 months for the third year and every 6 months for years
4 and 5.

Inclusion Criteria:

- 18 years of age or older

- History of biopsy documented prostate cancer (any Gleason score)

- Past treatment with prostatectomy with our without salvage prostate/pelvic radiation
or primary radiation

- If past prostatectomy, pathologic stage no greater than T1-3, N1, M0

- PSA recurrence with PSAdt 8 months or less. There is no minimum PSA for prostatectomy
patients. For patients treated with primary radiation therapy PSA should be 2.0ng/ml
or greater

- No evidence of recurrent disease on exam, bone scan, CT/MRI abdomen/pelvis on CXR

- Prior ADT allowed if less than 6 months and testosterone recovered to within 50 units
of normal range

- ECOG Performance status of 0-1

- Absolute neutrophil count of 1,500 mm3 or greater

- Platelet Count 100,000 mm3 or greater

- Total bilirubin within normal limits

- HG 8gm/dl or greater

- Testosterone within 50 units of normal range

- No history of bleeding or thromboses within the last 12 months that required medical
intervention

Exclusion Criteria:

- History of cancer within 5 years, other than prostate cancer and non-melanoma skin
cancer

- Medical condition requiring concomitant corticosteroids

- Active infection

- Prior chemotherapy

- Neuropathy requiring medical therapy

- Documented local recurrence or metastatic prostate cancer

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

- Life expectancy of less than 2 years

- Current, recent (within 4 weeks of first infusion of this study), or planned
participation in an experimental drug study other than a Genentech-sponsored Avastin
cancer study

- Inadequately controlled hypertension

- Any prior history of hypertensive crisis or hypertensive encephalopathy

- NYHA Grade II or greater congestive heart failure

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

- History of stroke or transient ischemic attack at any time

- Known CNS disease

- Significant vascular disease

- Symptomatic peripheral vascular disease

- Evidence of bleeding diathesis or coagulopathy

- 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 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

- Known hypersensitivity to any component of Avastin