This study will examine the effectiveness of combination therapy with docetaxel, prednisone, thalidomide, and bevacizumab in treating androgen-independent prostate cancer (cancer that does not respond to hormone therapy). Docetaxel is an anti-cancer drug. Prednisone is a steroid that has been used in the treatment of many types of cancer. Thalidomide, approved to treat leprosy, inhibits the formation of new blood vessels that feed tumors and has lessened pain and lowered PSA (a protein that is elevated in prostate cancer) levels in some patients with prostate cancer. Bevacizumab is a man-made antibody that inhibits new blood vessel growth and has been effective in treating several cancers, including prostate cancer.

Men 18 years of age and older with advanced androgen-independent prostate cancer may be eligible for this study. Candidates are screened with a medical history and physical examination, chest x-ray, CT scans and blood and urine tests.

Participants receive drug therapy in 3-week treatment cycles as follows:

- Docetaxel infusions intravenously (through a vein) over a 60-minute period on the first day of every cycle.

- Prednisone by mouth every day of the cycle

- Thalidomide by mouth every day of the cycle

- Bevacizumab intravenously on the first day of every cycle

In addition, patients take dexamethasone by mouth 12 hours and 1 hour before and 12 hours after the docetaxel to help prevent fluid retention caused by the drug, and the blood thinner enoxaparin once a day injected under the skin to prevent formation of blood clots that may be caused by bevacizumab and thalidomide.

Patients are seen at the NIH Clinical Center one day of each 3-week cycle for various tests and evaluations, including the following:

- Periodic blood and urine tests to monitor the response to treatment and drug side effects

- Possible magnetic resonance imaging (MRI) to determine the usefulness of this test for monitoring disease progress and response to treatment

- Possible bone marrow biopsy to look for cancer in this tissue

- Possible tumor biopsy (surgical removal of a small piece of tumor tissue) before treatment starts and after 2 months of treatment in patients who can safely undergo the procedure to look at the effect of treatment on the tumor and on blood vessel growth

Treatment response is evaluated approximately every 3 months using various tests, such as bone and CT scans. If there are no severe side effects and the cancer has not progressed, treatment may continue for more than 6 months. After six treatment cycles, patients have monthly chest x-rays to monitor possible fluid collecting around the lining of the lungs, which may occur in some patients who take docetaxel more 6 months or more.

Condition	Treatment or Intervention	Phase
Prostatic Neoplasms	Drug: Docetaxel  Drug: Thalidomide  Drug: Prednisone	Phase II

Further Study Details: 

Expected Total Enrollment:  60

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 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.

Genders Eligible for Study:  Male

Criteria

INCLUSION CRITERIA
Androgen-independent metastatic adenocarcinoma of the prostate defined as progressive metastatic disease while on GnRH agonists or post surgical castration
Histopathological documentation of prostate cancer confirmed in the NCI Laboratory of Pathology at the National Institutes of Health 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
Clinically progressive prostate cancer documented prior to entry. Progression must be documented by at least one of the following parameters:
-Two consecutively rising 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
ECOG performance status less than or equal to 2
Life expectancy of greater than 3 months
Patients must have adequate organ and marrow munction 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
AST(SGOT) and ALT(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 m2 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 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 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 CT or MRI brain scan.
Uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (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.
HIV-positive patients receiving combination anti-retroviral therapy are excluded fron the study because of possible pharmacokinetic interactions with docetaxel, bevacizumab, and/or the combination.
Proteinuria defined as a 24 hour urine protein excretion greater than 300 mg.
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.

Maryland
      National Cancer Institute (NCI), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  040257; 04-C-0257
Record last reviewed:  July 28, 2004
Last Updated:  November 23, 2004
Record first received:  August 6, 2004
ClinicalTrials.gov Identifier:  NCT00089609
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08