INCLUSION CRITERIA:
1. Patients must have histopathological confirmation of prostate cancer by the Laboratory of Pathology of the 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 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. 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)
AST(SGOT)/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 GnRH agonists or antagonists.
10. Patients must not have other invasive malignancies (within the past five 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 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 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. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AZD2171.
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 01/30/2009