Official Title: “Randomized Phase II Trial of Short-course Androgen Deprivation Therapy +/- Avastin for PSA Recurrence of Prostate Cancer After Definitive Local Therapy”

RATIONALE: Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as leuprolide, goserelin, and bicalutamide, may lessen the amount of androgens made by the body. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether hormone therapy is more effective when given with or without bevacizumab in treating prostate cancer.

PURPOSE: This randomized phase II trial is studying hormone therapy and bevacizumab to see how well they work compared with hormone therapy alone in treating patients with recurrent prostate cancer.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label

Study Primary Completion Date: July 2012

OBJECTIVES:

Primary - To identify a difference in relapse-free survival of patients with biochemically recurrent prostate cancer treated with short-course androgen-deprivation therapy with vs without bevacizumab.

Secondary - To determine the percentage of patients with a PSA < 0.2 ng/mL at 6 months after completion of treatment - To determine the cardiovascular safety of these regimens, including baseline and post-treatment measurements of BP and lipid profiles, in these patients. - To determine the safety profile of these regimens in these patients. - To analyze cytokines and angiogenic factors in plasma and/or serum samples.

OUTLINE: This is a multicenter study. Patients are stratified according to prior definitive local therapy (prostatectomy with or without salvage prostate/pelvic radiotherapy vs primary external-beam radiotherapy or brachytherapy), and age (< 60 years vs > 60 years). Patients are randomized to 1 of 2 treatment arms. - Arm I: Patients receive androgen-deprivation therapy comprising leuprolide intramuscularly or goserelin acetate subcutaneously every 3 months for 6 months AND oral bicalutamide once daily for 6 months. Patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment with bevacizumab repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. - Arm II: Patients receive androgen-deprivation therapy as in arm I. Patients may undergo blood sample collection at baseline and periodically during study for cytokine and angiogenic factor analysis by multiplex bead assays and ELISA.

After completion of study therapy, patients are followed up periodically.

Intervention(s) in this Clinical Trial

• Biological: bevacizumab
  • Given IV
• Drug: bicalutamide
  • Given orally
• Drug: goserelin
  • Given intramuscularly or subcutaneously
• Drug: leuprolide acetate
  • Given intramuscularly or subcutaneously

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Arm I
  • Patients receive androgen-deprivation therapy comprising leuprolide intramuscularly or goserelin acetate subcutaneously every 3 months for 6 months AND oral bicalutamide once daily for 6 months. Patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment with bevacizumab repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
• Active Comparator: Arm II
  • Patients receive androgen-deprivation therapy as in arm I.

Primary Measures

• Relapse-free survival
  • Safety Issue?: No

Secondary Measures

• Proportion of patients who attain a PSA of < 0.2 ng/mL
  • Safety Issue?: No
• Cardiovascular toxicity, weight gain, and insulin resistance as assessed by BP, lipid, glucose, and HgbA1C measurements
  • Safety Issue?: Yes
• Safety profile as assessed by NCI CTCAE v3.0
  • Safety Issue?: Yes
• Profile of cytokines and angiogenic factors in plasma and/or serum samples
  • Safety Issue?: No

DISEASE CHARACTERISTICS:

• Biopsy confirmed prostate cancer
• Any Gleason score allowed
• Has undergone prior prostatectomy (with or without salvage prostate/pelvic radiotherapy) OR primary radiotherapy (external beam radiotherapy or brachytherapy)
• Pathologic stage T1-3, N0-1, M0
• Rising PSA
• PSAdt < 18 months
• At least 3 PSA values required with ≥ 2 weeks between PSA values
• No evidence of local recurrence or metastatic disease on exam, bone scan, CT scan/MRI of abdomen/pelvis, or chest x-ray
• No known CNS disease

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Life expectancy ≥ 2 years
• ANC > 1,500/mm³
• Platelet count > 100,000/mm³
• Hemoglobin > 8 g/dL
• Urine protein:creatinine ratio < 1.0 OR < 2+ of protein by urine dipstick OR ≤ 1 g of protein by 24-hour urine collection
• No other cancer within the past 5 years except nonmelanoma skin cancer
• No medical condition requiring concurrent corticosteroids
• No active infection
• No inadequately controlled hypertension (defined as systolic BP > 150 mm Hg and/or diastolic BP > 100 mm Hg on antihypertensive medications)
• No prior hypertensive crisis or hypertensive encephalopathy
• No NYHA class II-IV congestive heart failure
• No myocardial infarction or unstable angina within the past 12 months
• No prior stroke or transient ischemic attack at any time
• No significant vascular disease (e.g., aortic aneurysm or aortic dissection)
• No symptomatic peripheral vascular disease
• No bleeding or thromboses that required medical intervention within the past 12 months
• No evidence of bleeding diathesis or coagulopathy (therapeutic anticoagulants allowed)
• No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
• No serious non-healing wound, ulcer, or bone fracture
• No known hypersensitivity to any component of bevacizumab
• No significant traumatic injury within the past 28 days

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Prior androgen-deprivation therapy allowed provided it was given for ≤ 6 months AND testosterone has recovered to within 50 units of normal range (i.e., if normal range is 250 to 850 ng/dL, a patient with testosterone of 200 to 900 ng/dL is eligible)
• At least 6 months since prior chemotherapy
• No more than 6 courses of prior chemotherapy
• More than 4 weeks since prior and no concurrent participation in another experimental drug study
• More than 4 weeks since prior major surgical procedure or open biopsy
• More than 7 days since prior core biopsy or other minor surgical procedure (other than placement of a vascular access device)
• No concurrent major surgical procedure

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Cancer Institute of New Jersey

Overall Clinical Trial Officials and Contacts

Robert S. DiPaola, MD Principal Investigator Cancer Institute of New Jersey  

Information obtained from ClinicalTrials.gov on February 08, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01019031

Study ID Number: CDR0000659681

ClinicalTrials.gov Identifier: NCT01019031

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database