A Phase II Study of BAY 43-9006 (Sorafenib) in Metastatic, Androgen-Independent Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: BAY 43-9006
Intervention description: 400 mg BAY 43-9006 orally twice daily in 28 day cycles.
Intervention MeSH terms: Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hormone-Refractory; Proteomics; Angiogenesis; VEGFR; Prostate Cancer; Metastatic Prostate Cancer

Summary:

      BAY 43-9006 (Sorafenib) is an experimental cancer drug produced by Bayer Health Care
      Corporation. It represents a new class of anticancer agents known as bi-aryl ureas. This
      study will investigate its effect on prostate cancer and its side effects. Researchers expect
      to enroll a maximum of 46 men with prostate cancer for this study. The duration of the study
      will depend on its results.

      Before beginning to take the drug, patients will be admitted to the hospital for 2 days, have
      a medical examination and give blood samples, and have a tumor or bone marrow biopsy. On the
      first day of the study, patients will begin taking the drug as 2 tablets twice daily, morning
      and evening. Blood will be taken throughout the day to determine the drug's level in the
      bloodstream.

      Patients will be discharged from the hospital on the second day, and will continue to take
      the drug twice daily until instructed to stop. During each of the first 4 weeks, patients
      will be required to have their blood pressure checked. At the end of the first 4 weeks,
      patients will have a physical examination and blood tests, as well as a second tumor or bone
      marrow biopsy.

      After the first 4 weeks, patients will continue with their drug regimen. At the end of each
      4-week cycle, patients will have a physical examination and blood tests. Patients will also
      have x-Rays, computed tomography (CT) scans, and/or magnetic resonance imaging (MRIs) at
      every other 4-week examination or as required. Patients will be asked to keep a diary
      recording the time and amount of their medication for this study.
    

Eligibility criteria:

        -  INCLUSION CRITERIA

        Patients must have histopathological confirmation of prostate cancer by the Laboratory of
        Pathology of the National Cancer Institute (NCI) or Pathology Department of the National
        Naval Medical Center prior to entering this study. Patients whose pathology specimens are
        no longer available may be enrolled in the trial if the patient has a clinical course
        consistent with prostate cancer and available documentation from an outside pathology
        laboratory of the diagnosis. In cases where original tissue blocks or archival biopsy
        material is available, all efforts should be made to have the material forwarded to the
        research team for use in correlative studies.

        Patients must have metastatic progressive androgen-independent prostate cancer. There must
        be radiographic evidence of disease after primary treatment with either surgery or
        radiotherapy that has continued to progress despite hormonal agents. Progression requires
        that a measurable lesion is expanding, new lesions have appeared, and/or that prostatic
        specific antigen (PSA) is continuing to rise on successive measurements. Patients on
        flutamide must have disease progression at least 4 weeks after withdrawal. Patients on
        bicalutamide or nilutamide must have progression at least 6 weeks after withdrawal.

        Patients may have had no more than 1 previous cytoxic chemotherapeutic line.

        Because no dosing or adverse event data are currently available on the use of BAY 43-9006
        (Sorafenib) in patients less than 18 years of age, children are excluded from this study.

        Patients must have a life expectancy of more than 3 months.

        Patients must have a performance status of 0 to 2 according to the Eastern Cooperative
        Oncology Group (ECOG) criteria.

        Patient must have adequate organ function as defined below:

        Leukocytes greater than or equal to 3,000/microL

        Absolute neutrophil count greater than or equal to 1,500/microL

        Platelets greater than or equal to 100,000/microL

        Total bilirubin less than or equal to 1.5 X 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
        X institutional upper limit of normal

        Creatinine less than or equal to 1.5 X institutional upper limits of normal OR:

        Creatinine clearance greater than or equal to 60 mL/min/1.73 m^2 for patients with
        creatinine levels above institutional normal.

        Patients must have recovered from any acute toxicity related to prior therapy, including
        surgery. Toxicity should be less than or equal to grade 1 or returned to baseline.

        Hormonal profile: all patients who have not undergone bilateral surgical castration must
        continue suppression of testosterone production by appropriate usage of gonadotropin
        releasing hormone (GnRH) agonists.

        Patients must not have other invasive malignancies (within the past two years with the
        exception of non-melanoma skin cancers or non-invasive bladder cancer).

        Patients must be able to understand and sign an informed consent form.

        Concurrent use of bisphosphonates will be allowed for patients with known bone metastases

        Patients who require hematopoietic growth factor support (e.g. epogen, darbepoetin),
        non-steroidal anti-inflammatory drug (NSAIDs), and other maintenance medications prior to
        study entry will be allowed to continue their supportive therapies.

        The effects of BAY 43-9006 (Sorafenib) on the developing human fetus at the recommended
        therapeutic dose are unknown. For this reason and because Raf-kinase inhibitors are known
        to be teratogenic, men must agree to use adequate contraception (abstinence; hormonal or
        barrier method of birth control) prior to study entry and for the duration of study
        participation.

        EXCLUSION CRITERIA

        Patients who have had chemotherapy or radiotherapy (including radioisotopes) within 4 weeks
        (6 weeks for nitrosoureas or mitomycin C, greater than 3 months for suramin) prior to
        entering the study or those who have not recovered from adverse events due to agents
        administered more than 4 weeks earlier.

        Patients may not be receiving any other investigational agents.

        Patients with known brain metastases are excluded from this clinical trial because of their
        poor prognosis and because they often develop progressive neurologic dysfunction that would
        confound the evaluation of neurologic and other adverse events.

        History of allergic reactions attributed to compounds of similar chemical or biologic
        composition to BAY 43-9006 (Sorafenib)

        Uncontrolled intercurrent illness including, but not limited to ongoing or active
        infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
        arrhythmia, or psychiatric illness/social situations that would limit compliance with study
        requirements.

        Hypertension as defined by systolic blood pressure in excess of 170 mmHg or diastolic
        pressure in excess of 100 mmHg. Patients with a history of hypertension that is well
        controlled on medication will not be excluded. Patients may not be on either verapamil or
        diltiazem while on study. Use of calcium channel blocker should be discouraged.

        Patients with immune deficiency are at increased risk of lethal infections when treated
        with marrow-suppressive therapy. Therefore, human immunodeficiency virus (HIV)-positive
        patients receiving combination anti-retroviral therapy are excluded from the study because
        of possible pharmacokinetic interactions with BAY 43-9006 (Sorafenib). Appropriate studies
        will be undertaken in patients receiving combination anti-retroviral therapy when
        indicated.

        History of bleeding diathesis

        Patients on therapeutic anticoagulation are at increased risk from bleeding while on BAY
        43-9006 (Sorafenib). Prophylactic anticoagulation (i.e. low dose warfarin) of venous or
        arterial access devices is allowed provided that the requirements for prothrombin time
        (PT), International normalized ratio (INR) or partial thromboplastin time (PTT) are met: PT
        less than 1.1 x institutional upper limit of normal; INR less than 1.1; PTT within the
        institutional limits of normal. These requirements will only be made upon those patients on
        warfarin.

        INCLUSION OF WOMEN AND MINORITIES

        Men of all races and ethnic groups are eligible for this trial. Women are excluded by the
        nature of the disease.