AZD2171 to Treat Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Magnetic Resonance Imaging (DCE-MRI); AZD2171; Prednisone
Intervention description: Scans evaluate tumor tissue and blood flow.; 20 mg oral daily for 28 days; 10mg orally daily in combination with AZD2171 20mg daily.
Intervention MeSH terms: Prednisone; Cediranib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 59.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: VEGF; Angiogenesis; Hormone-Refractory; Bone Metastases; Docetaxel-Resistant; Prostate Cancer

Summary:

      Background:

        -  AZD2171 (Cediranib) is an experimental drug that inhibits formation of new blood
           vessels.

        -  Tumors need new blood vessels to grow. Preventing the growth of new blood vessels with
           AZD2171 may inhibit tumor growth.

      Objectives:

      -To determine the effectiveness and side effects of AZD2171 in patients with prostate cancer
      that has metastasized (spread beyond the primary site).

      Eligibility:

        -  Males 18 years of age and older with androgen-independent prostate cancer that has
           metastasized.

        -  Patients must have received prior treatment with docetaxel.

      Design:

      Patients take one AZD2171 by mouth every day in 28-day treatment cycles and undergo the
      following procedures:

        -  1- to 2-day hospitalization at the start of the study for biopsies and blood
           measurements to determine the level of AZD2171 in the bloodstream. Blood is drawn
           immediately before the first dose, and 0.25 hr, 0.5 hr, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12
           hr, 24 hr, and 48 hours after the dose is taken.

        -  Blood tests before starting treatment and then monthly to determine the level of
           vascular endothelial growth factor receptor ( VEGFR), a protein involved in blood vessel
           formation.

        -  Magnetic resonance imaging (MRI) scans once a month to evaluate blood flow.

        -  Tumor biopsies (optional) both before and after the second and sixth treatment cycles.

        -  Clinic visits every 4 weeks, including various routine and research blood tests, urine
           test and electrocardiogram.

        -  Computed tomography (CT) scan of the chest, abdomen, and pelvis every 8 weeks

        -  Bone scan every 8 weeks

      Patients record all doses of AZD2171 taken or missed in a pill diary. They record their blood
      pressure at least once daily in a blood pressure diary.

      Treatment may continue as long as the patient tolerates the AZD2171 and the cancer does not
      worsen.

      ...
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. Patients must have histopathological confirmation of prostate cancer by the
                  Laboratory of Pathology of the National Cancer Institute (NCI), Pathology
                  Department of the National Naval Medical Center or Pathology Department of Walter
                  Reed Army 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.

               2. Patients must have metastatic progressive androgen-independent prostate cancer.
                  There must be radiographic evidence of disease 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.

               3. Patients must have received prior therapy with docetaxel for androgen-independent
                  prostate cancer. Any number of prior treatments are acceptable.

               4. Age greater than or equal to 18 years.

               5. Life expectancy of greater than 3 months.

               6. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal
                  to 2 (Karnofsky greater than or equal to 60%).

               7. Patients must have normal organ and marrow function as defined below:

                  Absolute neutrophil count greater than or equal to 1,500/mcL

                  Platelets greater than or equal to 100,000/mcL

                  Hemoglobin greater than or equal to 8 g/dL

                  Total bilirubin within normal institutional limits (unless with clinical
                  Gilbert's syndrome)

                  Aspartate aminotransferase/serum glutamic oxaloacetic transaminase
                  (AST(SGOT))/alanine aminotransferase/serum glutamic pyruvic transaminase
                  (ALT(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 normal
                  institutional limits

                  OR

                  Creatinine clearance greater than 40 mL/min/1.3 m^2 for patients with creatinin
                  levels above institutional normal as calculated by the Cockcroft Gault formula.

               8. 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.

               9. All patients who have not undergone bilateral surgical castration must continue
                  suppression of testosterone production by appropriate usage of gonadotropin
                  releasing hormone (GnRH) agonists or antagonists.

              10. Patients must not have other invasive malignancies (within the past three years
                  with the exception of non-melanoma skin cancers or non-invasive bladder cancer).

              11. AZD2171 has been shown to terminate fetal development in the rat, as expected for
                  a process dependent on VEGF signaling. Enrolled patients must agree to use
                  adequate contraception (hormonal or barrier method of birth control; abstinence)
                  prior to study entry, the duration of study participation and 3 months after the
                  end of the treatment.

              12. Ability to understand and the willingness to sign a written informed consent
                  document.

              13. Patients must have a blood pressure of less than 140/90 at the time of
                  enrollment. Details of antihypertensive treatment, if required, will be left up
                  to the primary care physician.

        EXCLUSION CRITERIA:

          1. Patients who have had chemotherapy, radiotherapy, or major surgery within 4 weeks (6
             weeks for nitrosoureas or mitomycin C) prior to entering the study.

          2. Patients may not be receiving any agents not approved by the Food and Drug
             Administration (FDA) within the past four weeks.

          3. Patients with known brain metastases should be 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.

          4. Mean QTc greater than 470 msec (with Bazett's correction) in screening
             electrocardiogram or history of familial long Q wave, T wave (QT) syndrome.

          5. Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week
             apart.

          6. Uncontrolled intercurrent illness including, but not limited to hypertension, 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.

          7. Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
             therapy are ineligible because of the potential for pharmacokinetic interactions with
             AZD2171.