AZD2171 to Treat Prostate Cancer

• Status: Completed
• Trial end date: 2014-02-05
• Target enrollment: 0
• Participant gender: Male

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.

...

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Cediranib; Prednisone

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.