Satraplatin and Prednisone to Treat Prostate Cancer
Condition: Prostate Cancer; Genetic Polymorphism
MeSH terms: Prostatic Neoplasms
Intervention: Satraplatin; prednisone
Intervention description: 80 mg/m^2 days 1-5 of every 35 day cycle; 5 mg twice daily every 35 days
Intervention MeSH terms: Prednisone; Satraplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Chemotherapy; Pharmacokinetics; Gene Polymorphisms; Prostate Cancer

Summary:

      Background:

      Satraplatin is an experimental drug that may be of benefit to patients with prostate cancer.

      Prednisone is approved for treating prostate cancer.

      The gene excision repair cross-complementing rodent repair deficiency complementation group 1
      (ERCC1) helps repair cell damage caused by satraplatin. It is possible that patients who have
      a variant of this gene will not benefit from treatment with satraplatin because the drug will
      not be able to damage the cancer cells effectively.

      Objectives:

      To determine if satraplatin may help treat prostate cancer in patients with certain variants
      of the ERCC1 gene.

      Eligibility:

      Patients with advanced androgen-independent prostate cancer whose disease has not responded
      to hormonal therapy or at least one type of chemotherapy and whose x-rays, scans or other
      tests have shown their cancer to be spreading.

      Design:

      Participants have a blood test to determine if they have a variant of the ERCC1 gene.

      Participants take satraplatin by mouth every day for 5 consecutive days out of every 35 days
      and prednisone by mouth every day. These 35-day treatment cycles may continue for 6 months or
      longer, depending on the benefits and side effects of the treatment.

      During the treatment period, patients undergo the following tests and procedures:

        -  Blood tests on days 1 of the treatment cycle.

        -  Weekly blood draws for the first 3 treatment cycles.

        -  Imaging studies (e.g., bone scans, computed tomography (CT) scans) every two cycles to
           determine the response to treatment.

        -  Surgical or medical suppression of testosterone in patients whose cancer cells continue
           to grow due to exposure to the hormone....
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        A. 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 or Walter Reed Army Medical Center prior to entering this study.
        Patients whose pathology specimens are not 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.

        B. Patients must have metastatic progressive androgen-independent prostate cancer. There
        must be radiographic evidence of disease (by computed tomography (CT) scan or bone scan)
        after primary treatment 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
        must have progressive disease after receiving 1 prior docetaxel-based cytotoxic
        chemotherapy. Patients on flutamide for the prior 6 months must have disease progression at
        least 4 weeks after withdrawal. Patients on bicalutamide or nilutamide must have
        progression at least 6 weeks after withdrawal.

        C. Patients may only have received 1 prior cytotoxic chemotherapy. For the purpose of this
        study, multiple courses of a taxane-based regimen may count as a single regimen. Multiple
        courses of a non-taxane agent or a combination chemotherapy regimen, administered in a
        similar fashion may count as a single regimen.

        D. Patients must have a life expectancy of more than 3 months.

        E. Patients must have a performance status of 0 to 2 according to the Eastern Cooperative
        Oncology Group (ECOG) criteria.

        F. Patients 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 times institutional upper limits of normal
        (Except patients with Gilbert's disease who may proceed despite elevated total bilirubin).

        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 institutional upper limit of normal

        Creatinine less than or equal to 1.5 times 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.

        G. Patients must have recovered from any acute toxicity related to prior therapy, including
        surgery. Toxicity should be <= grade 1 or returned to baseline.

        H. 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.

        I. Patients must not have any ongoing malignancies requiring active therapy.

        J. Patients must be able to understand and sign an informed consent form.

        K. Concurrent use of bisphosphonates will be allowed if patients have previously been on
        it; if patients are not on bisphosphonates at the time of study enrollment, bisphosphonates
        may be started at cycle 2.

        L. Patients who require hematopoietic growth factor support (e.g. epogen, darbepoetin), but
        not myeloid growth factors (except after cycle 1 day 1 if clinically indicated),
        non-steroidal anti-inflammatory drug (NSAIDs), and other maintenance medications prior to
        study entry will be allowed to continue their supportive therapies.

        M. Results from embryo-fetal development indicated that satraplatin should be considered a
        teratogen in women of childbearing potential and hazardous in respect to spermatogenesis
        for men. For this reason, 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.

        N. Patients must be able to swallow capsules.

        O. Patients on chronic stable steroids (equivalent to no more than 10 mg of prednisone
        daily dose) used for non-cancer treatment may be allowed on study.

        EXCLUSION CRITERIA:

        A. Patients who have had prior treatment with satraplatin or other platinum containing
        compounds will be excluded.

        B. Patients may not be receiving any other investigational agents.

        C. Patients with known active 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.

        D. History of allergic reactions attributed to compounds of similar chemical or biologic
        composition to satraplatin or prednisone.

        E. Uncontrolled intercurrent illness including, but not limited to ongoing or active
        serious infection, symptomatic congestive heart failure, unstable angina pectoris, or
        psychiatric illness/social situations that would limit patient compliance with study
        requirements.

        F. Prior radiation therapy to greater than 30 percent of the bone marrow, or who have
        received strontium-89, rhenium-186, or rhenium-188 will be excluded from this trial.
        Patients who have received prior radiotherapy must have recovered from acute toxicity due
        to radiation. Patients who have received samarium-153 are eligible for the study because
        samarium has a significantly reduced half-life compared to aforementioned isotopes.

        G. Patients with immune deficiency are at increased risk of lethal infections when treated
        with marrow-suppressive therapy. Therefore, human immunodeficiency virus (HIV)-positive
        patients are excluded from the study.

        H. Patients with a history of major gastrointestinal surgery or pathology likely to
        influence absorption of oral medications, like bypass surgeries, Whipple's procedure, or
        any surgery that would impair reliable absorption of oral drugs.

        I. Patients with a disease where corticosteroids are contraindicated, e.g. active gastric
        or duodenal ulcer, or poorly controlled insulin dependent diabetes. Patients with
        well-controlled insulin-dependent diabetes mellitus may be considered, providing they
        understand their glucose levels will increase, and their insulin dose will require
        adjusting.

        J. Because no dosing or adverse event data are currently available on the use of
        satraplatin in patients less than 18 years of age, children are excluded from this study.