Docetaxel and Prednisone With or Without Cediranib in Treating Patients With Metastatic Prostate Cancer That Did Not Respond to Hormone Therapy
Condition: Adenocarcinoma of the Prostate; Stage IV Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: cediranib maleate; docetaxel; prednisone; laboratory biomarker analysis
Intervention description: Given orally; Given IV; Given orally; Correlative studies
Intervention MeSH terms: Prednisone; Docetaxel; Cediranib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 57.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial is studying how well giving docetaxel and prednisone together
      with or without cediranib works in treating patients with metastatic prostate cancer that did
      not respond to hormone therapy. Drugs used in chemotherapy, such as docetaxel and prednisone,
      work in different ways to stop the growth of tumor cells, either by killing the cells or by
      stopping them from dividing. Cediranib may stop the growth of tumor cells by blocking some of
      the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving docetaxel
      together with prednisone, with or without cediranib, may kill more tumor cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Clinical/radiologic metastases with objective evidence of disease progression by
             imaging or by rising prostate-specific antigen (PSA) despite androgen deprivation
             therapy

          -  Rising PSA must be determined based on a rising trend with 2 successive elevations at
             a minimum interval of 1 week

          -  Meets 1 of the following criteria: Measurable disease, with any level of PSA, at least
             1 unidimensionally measurable lesion (longest diameter to be recorded) >= 20 mm by
             conventional techniques or >= 10 mm by spiral CT scan, nonmeasurable disease, PSA >= 5
             ng/mL OR new areas of bony metastases on bone scan

          -  Castrate levels of testosterone < 50 ng/dL must be maintained and documented

          -  Luteinizing hormone-releasing hormone (LHRH) agonist therapy must be continued, if
             required to maintain castrate levels of testosterone

          -  Total bilirubin normal

          -  Patients with radiological evidence of stable brain metastases are eligible provided
             they are asymptomatic and do not require corticosteroids or have been treated with
             corticosteroids and show clinical and radiological evidence of stabilization at least
             10 days after discontinuation of steroids

          -  ECOG performance status (PS) =< 2 or Karnofsky PS 60-100%

          -  Life expectancy > 12 weeks

          -  Leukocytes >= 3,000/mcL

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelet count >= 100,000/mcL

          -  Histologically confirmed adenocarcinoma of the prostate

          -  AST and ALT =< 2.5 times upper limit of normal

          -  Creatinine normal OR creatinine clearance >= 60 mL/min

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  Proteinuria =< 1+ and urine protein:creatinine ratio =< 1.0 OR 24-hour urine protein <
             1,000 mg

          -  Peripheral neuropathy >= grade 2

          -  Uncontrolled intercurrent illness including, but not limited to, any of the following:
             ongoing or active infection, symptomatic congestive heart failure, unstable angina
             pectoris, cardiac arrhythmia, psychiatric illness/social situations that would limit
             compliance with study requirements

          -  Congestive heart failure, second or third degree heart block, or recent myocardial
             infarction within the past 6 months

          -  QTc prolongation > 500 msec OR other ECG abnormality noted within 14 days of treatment

          -  New York Heart Association class III or IV cardiac disease; Class II disease
             controlled with treatment and monitoring allowed

          -  History of poorly controlled hypertension (e.g., resting blood pressure > 150/90 mm Hg
             with or without hypertensive therapy)

          -  History of a curatively treated malignancy with a survival prognosis of less than 5
             years or concurrent malignancy except for adequately treated basal cell or squamous
             cell skin cancer or carcinoma in situ

          -  History of significant gastrointestinal impairment, as judged by the investigator,
             that would significantly affect the absorption of cediranib

          -  History of severe hypersensitivity reaction to docetaxel or other drugs formulated
             with polysorbate 80

          -  Significant hemorrhage (30 mL bleeding/episode in previous 3 months) or hemoptysis (5
             mL fresh blood in previous 4 weeks)

          -  Prior enrollment or randomization of treatment in the present study

          -  Patients must be off flutamide antiandrogen therapy for ≥ 4 weeks (6 weeks for
             bicalutamide or nilutamide)

          -  No prior chemotherapy for metastatic prostate cancer

          -  No major surgery within the past 14 days or a surgical incision that is not fully
             healed

          -  No HIV-positive patients on combination antiretroviral therapy

          -  No conditions requiring concurrent use of drugs or biologics with proarrhythmic
             potential

          -  No other investigational agents within 30 days prior to study enrollment

          -  No untreated unstable brain or meningeal metastases

          -  Known hypersensitivity to cediranib or any of its excipients