Docetaxel, Thalidomide, Prednisone, and Bevacizumab to Treat Metastatic Prostate Cancer
Condition: Prostatic Neoplasms
MeSH terms: Prostatic Neoplasms
Intervention: Docetaxel; Thalidomide; Prednisone; bevacizumab; polymorphism analysis; immunoenzyme technique; laboratory biomarker analysis; pharmacological study
Intervention description: Docetaxel 75 mg/m^2 intravenously over 60 minutes on cycle 1 day 1 repeated every 21 days.; Thalidomide 200 mg by mouth daily throughout the cycle.; Prednisone 10 mg by mouth daily throughout the cycle.; Bevacizumab 15 mg/kg intravenously on cycle 1 day 1 every 21 days.; Two buffy coat tubes (two 7mL blue tiger top tubes) will be obtained and wrapped in foil when the patient enters onto the study. DNA (deoxyribonucleic acid) will be isolated only for the purpose of genotype analysis of enzymes with putative relevance for docetaxel or thalidomide disposition.; The PBMC (peripheral blood mononuclear cells) of patients will be analyzed pre-treatment and post cycle 2 for any changes in the function of regulatory T cells. The following analysis will be performed: flow cytometry analysis, CD4 CD25 T cell enrichment, and immunosuppression assay.; Serum and urine samples will be collected at baseline and monthly to measure VEGF (vascular endothelial growth factor) levels.; Plasma concentrations of docetaxel and thalidomide will be determined to assess interactions between docetaxel (and thalidomide) and the concomitant therapy.The analysis will be performed using a validated method based on liquid chromotography with mass-spectrometric detection.
Intervention MeSH terms: Thalidomide; Prednisone; Bevacizumab; Docetaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 73.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hormones; Angiogenesis; Markers; Tumor; Prostate Cancer

Summary:

      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.
    

Eligibility criteria:

        -  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.