Bevacizumab With Hormonal and Radiotherapy for High-Risk Prostate Cancer

Pilot Phase II Trial of Bevacizumab in Combination With Hormonal and Radiotherapy in Patients With High-Risk Prostate Cancer

The purpose of this study is to determine the acute and late toxicities from radiation therapy in combination with bevacizumab (given every 2 weeks for 16 weeks then every 3 weeks for 12 weeks), bicalutamide (every day for 16 weeks) and goserelin (every 3 months for 2 years).

Although there is no data on the toxicity with concurrent bevacizumab and hormonal therapy, the combination is not expected to increase toxicity seen when given as a single agent. Abnormal tumor microenvironments, tumor progression, and metastatic spread are major factors contributing to treatment failures in radiotherapy. Anti-VEGF agents (e.g. bevacizumab) can help overcome these factors through several different mechanisims.

Studies also demonstrate prolonged use of anti-VEGF agents with radiation therapy was more effective at preventing metastases from irradiated tumors compared to a short course. Patients generally start hormonal therapy and daily radiotherapy at the same time. This study will delay the start of radiotherapy until 8 weeks after the start of hormonal therapy and bevacizumab.

Inclusion Criteria:

• High Risk Prostate Cancer as defined as ONE of the following:

  1. Clinical T2b-T4
  2. Gleason sum score 8-10
  3. PSA more than 20 and Gleason sum score 7
  4. In addition, clinical T2a patients are eligible if 5 or more biopsies contain Gleason 4+3 cancer (minimum of 10 biopsies total required)

• No evidence of metastatic disease within 60 days of enrollment, confirmed by physical examination, chest x-ray, bone scan, and computed tomography of the abdomen and pelvis

• ECOG performance status of 0, 1 or 2

Exclusion Criteria:

• Concurrent or prior treatment with radiation, cytotoxic, biologic therapy for prostate cancer; any major surgery within four weeks, prior hormonal therapy (except finasteride for obstructive voiding symptoms)
• 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; Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to Day 0
• Presence of central nervous system or brain metastases
• Blood pressure of >150/100 mmHg
• History of myocardial infarction within 6 months
• History of stroke within 6 months
• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study