Docetaxel, Thalidomide, Prednisone, and Bevacizumab to Treat Metastatic Prostate Cancer
Docetaxel, Thalidomide, Prednisone, and Bevacizumab to Treat Metastatic Prostate Cancer
This is a Phase II study of docetaxel, bevacizumab, prednisone and thalidomide in patients
 with androgen independent metastatic prostate cancer who are previously untreated with
 chemotherapy. The primary objective of this study is to determine if the combination of
 docetaxel, thalidomide and bevacizumab is able to be associated with a sufficiently high
 proportion of patients with a prostate-specific antigen (PSA) response to be worthy of
 further investigation in metastatic prostate cancer. We will also be looking at multiple
 secondary endpoints. These will include possible pharmacokinetic interactions among the study
 agents, potential correlation between patient genotype and efficacy of treatment. We will
 also be looking for circulating tumor cells in blood before and after treatment. Additionally
 we will be monitoring the tolerability of the regimen and survival duration as endpoints as
 well. We hope to use this trial to build on the promising results seen in our
 thalidomide/docetaxel protocol where there was a significant PSA decline and a trend toward
 survival benefit.
This is a Phase II study of docetaxel, bevacizumab, prednisone and thalidomide in patients
 with androgen independent metastatic prostate cancer who are previously untreated with
 chemotherapy. The primary objective of this study is to determine if the combination of
 docetaxel, thalidomide and bevacizumab is able to be associated with a sufficiently high
 proportion of patients with a PSA response to be worthy of further investigation in
 metastatic prostate cancer. We will also be looking at multiple secondary endpoints. These
 will include possible pharmacokinetic interactions among the study agents, potential
 correlation between patient genotype and efficacy of treatment. We will also be looking for
 circulating endothelial cells in blood before and after treatment. Additionally we will be
 monitoring the tolerability of the regimen, time to disease progression, and survival
 duration as endpoints as well. We hope to use this trial to build on the promising results
 seen in our thalidomide/docetaxel protocol where there was a significant PSA decline and a
 trend toward survival benefit.
-  INCLUSION CRITERIA:

 Androgen-independent metastatic adenocarcinoma of the prostate defined as progressive
 metastatic disease while on gonadotropin releasing hormone (GnRH) agonists or post surgical
 castration

 Histopathological documentation of prostate cancer confirmed in the National Cancer
 Institute (NCI) Laboratory of Pathology at the National Institutes of Health, the Pathology
 Department at Walter Reed Medical Center or the Pathology Department at National Naval
 Medical Center, prior to starting this study. In addition, patients whose slides are lost
 or unavailable will be eligible for the study if they provide documentation of prostate
 cancer and if they meet criteria of clinically progressive prostate cancer as outlined in
 section 3.1.1.3.

 Clinically progressive prostate cancer documented prior to entry. Progression must be
 documented by at least one of the following parameters:

 -  Two consecutively rising prostate-specific antigen (PSA) levels. The first rising PSA
 must be a minimum of one week from a reference value. It is recognized that PSA
 fluctuations are such that the confirmatory PSA value might be less than the previous
 one. In these cases, that patient would still be eligible provided the next PSA was
 greater than the first rising PSA value. Patients must have PSA greater than or equal
 to 5.0.

 -  At least one new lesion on bone scan.

 -  Progressive measurable disease.

 Patients must have undergone bilateral surgical castration or must continue on GNRH
 agonist.

 Those patients receiving an anti-androgen agent and are entering the trial due to a rise in
 PSA must demonstrate a continued rise in PSA 4 weeks after stopping flutamide and 6 weeks
 after stopping bicalutamide or nilutamide.

 Patients may not have received any chemotherapy for metastatic prostate cancer

 Age greater than or equal to 18 years

 Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2

 Life expectancy of greater than 3 months

 Patients must have adequate organ and marrow function as defined below:

 Leukocytes- greater than or equal to 3,000/microliter

 Absolute neutrophil count- greater than or equal to 1,500/microliter

 Platelets- greater than or equal to 100,000/microliter

 Hemoglobin- greater than or equal to 8.0g/L - transfusions acceptable

 Total bilirubin- less than or equal to 1.5 times the institutional upper limits of normal

 Aspartate aminotransferase (AST)serum glutamic oxaloacetic transaminase(SGOT) and alanine
 aminotransferase (ALT)serum glutamic pyruvic transaminase(SGPT) - less than or equal to 2.5
 times the institutional upper limits of normal

 Creatinine or Creatinine clearance- less than or equal to 1.5 times the institutional upper
 limits of normal or greater than or equal to 40 mL/min/1.73 m^2 for patients with
 creatinine levels above institutional normal.

 Recovered from any toxicity from surgery or radiotherapy

 Must be willing to travel from their home to the National Institutes of Health (NIH) for
 follow-up visits

 Able and willing to follow instructions and conform to protocol.

 Patients may have had no other active malignancy within the past 2 years with the exception
 of non-melanoma skin cancer and superficial bladder carcinoma

 No history of myocardial infarction within the past 6 months, uncontrolled congestive heart
 failure (CHF) or uncontrolled angina pectoris

 Patients must agree to use adequate contraception (abstinence; hormonal or barrier method
 of birth control) for the study and at least 2 months after completion.

 Ability to understand and the willingness to sign a written informed consent document.

 EXCLUSION CRITERIA:

 Present clinical signs or symptoms of brain and/or leptomeningeal metastases confirmed by
 computed tomography (CT) or magnetic resonance imaging (MRI) brain scan.

 Uncontrolled, intercurrent illness including, but not limited to, ongoing or active
 infection, symptomatic congestive heart failure (American Heart Association (AHA) Class II
 or worse), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social
 situations that would limit compliance with study requirements

 Persistent systolic blood pressure greater than or equal to 170 mmHg or diastolic blood
 pressure greater than or equal to 100 mmHg.

 Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral
 therapy are excluded from the study because of possible pharmacokinetic interactions with
 docetaxel, bevacizumab, and/or the combination.

 Proteinuria, as demonstrated by a urine, protein, creatinine (UPC) ratio greater than or
 equal to 1.0 at screening, required to be assessed if urine dipstick is greater than or
 equal to 1+.

 Urine protein should be screened by urine analysis for Urine Protein Creatinine (UPC)
 ratio. For UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should
 be < 1000 mg for patient enrollment. Note: UPC ratio of spot urine is an estimation of the
 24 urine protein excretion - a UPC ratio of 1 is roughly equivalent to a 24-hour urine
 protein of 1 gm. UPC ratio is calculated using one of the following formula:

 -  [urine protein]/[urine creatinine] - if both protein and creatinine are reported in
 mg/dL

 -  [(urine protein) x 0.088]/[urine creatinine] - if urine creatinine is reported in
 mmol/L

 Therapeutic anticoagulation with coumadin, heparins, or heparinoids.

 Greater than Grade 2 peripheral neuropathy at baseline.

 History of transient ischemic attacks (TIA) or cerebrovascular accident (CVA) within the
 past 2 years.

 History of allergic reaction to docetaxel, prednisone, thalidomide and/or bevacizumab or
 related products.

 Patients who are on concurrent investigational agent(s)

 Patients who are unable to ingest oral medication.

 INCLUSION OF WOMEN AND MINORITIES

 Men of all races and ethnic groups are eligible for this trial. Every effort will be made
 to recruit minorities in this study. Women are ineligible for this study.