AZD2171 to Treat Prostate Cancer
- Conditions
- Prostate Cancer
- Interventions
- Registration Number
- NCT00436956
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief 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.
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- Detailed Description
Background:
* AZD2171 (Cediranib) is an oral potent inhibitor of receptor tyrosine kinases which impact vascular endothelial growth factor-A (VEGF).
* VEGF appears important in blood vessel formation and disease progression in prostate cancer.
* No known effective therapy in patients with progressive androgen-independent prostate cancer after treatment with docetaxel.
Objectives:
* Primary objective of this study is to determine if AZD2171 is associated with a 30% 6 month probability of progression free survival in patients with metastatic androgen independent prostate cancer (AIPC) as determined by clinical and radiographic criteria.
* Secondary objective of this study will be demonstration of biologic effect by the drug in the patient and on the tumor (when possible). Correlative studies will be conducted on serially obtained tissue biopsies and white blood cell collections.
* Laboratory correlates will include elucidation of activation of components of the VEGFR2 and angiogenesis pathways and evaluation of endothelial cell adhesion molecules (released by damaged cells) using enzyme-linked immunosorbent assay (ELISA), pharmacogenetic analysis of kinase insert domain receptor (KDR) variants and single nucleotide polymorphisms, and pharmacokinetic characterization of AZD2171 activity.
Eligibility:
* Metastatic progressive androgen-independent prostate cancer.
* Prior treatment with docetaxel.
* May not have corrected QT interval (QTc ) greater than 470 msec or greater than 1+ proteinuria on 2 consecutive dipsticks no less than 1 week apart.
Design:
* Phase II trial with a two stage design. 12 patients enrolled in first cohort, if 2 or more are progression free at 6 months than enroll up to 35 evaluable patients. The ceiling will be set at 37 to allow for inevaluable patients.
* Starting dose 20 mg QD (every day) for all patients.
* Once two stage design is complete then prednisone 10 mg once per day will be given in combination with AZD2171. The total number of patients will be 23 for this portion of the protocol.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 59
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description AZD2171 in Prostate Cancer AZD2171 Cohort 1 (n=35) received 20 mg AZD2171 (Cediranib) orally daily. Cohort 2 (n=23) received prednisone 10 mg orally daily with 20 mg AZD2171. AZD2171 in Prostate Cancer Magnetic Resonance Imaging (DCE-MRI) Cohort 1 (n=35) received 20 mg AZD2171 (Cediranib) orally daily. Cohort 2 (n=23) received prednisone 10 mg orally daily with 20 mg AZD2171. AZD2171 in Prostate Cancer Prednisone Cohort 1 (n=35) received 20 mg AZD2171 (Cediranib) orally daily. Cohort 2 (n=23) received prednisone 10 mg orally daily with 20 mg AZD2171.
- Primary Outcome Measures
Name Time Method Percent Probability of Participants With 6-month Progression-free Survival (PFS) 6 months PFS is the proportion of subjects who progress or die by 6 months after the start of the combined therapy. PFS is determined by prostatic specific antigen (PSA) consensus criteria and the Response Evaluation Criteria in Solid Tumors (RECIST). PSA consensus criteria is defined as PSA decline of \>/= 50% or PSA progression. RECIST is defined as the following: Complete response (CR) is disappearance of all target lesions; partial response (PR) is at least a 30% decline in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; and stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease ((PD) at least a 20% increase in the sum of the LD of target lesions, or the appearance of one or more lesions), taking as reference the smallest sum LD since the treatment started. Data is estimated and the probability of PFS as a function of time was determined using the Kaplan-Meier method.
- Secondary Outcome Measures
Name Time Method Number of Participants With Adverse Events Date treatment consent signed to date off study, approximately 61.5 months Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Number of Grade 2 Toxicities 61.5 months Here is the number of Grade 2 (moderate) toxicities.
Number of Grade 3 Toxicities 61.5 months Here is the number of Grade 3 (severe) toxicities.
Median Overall Survival 44 months Time from treatment start date until date of death or date last known alive.
Median Progression Free Survival (PFS) up to 14.9 months based on a Kaplan-Meier analysis. Time interval from start of treatment to documented evidence of disease progression.
Response Per the Response Evaluation Criteria in Solid Tumors (RECIST) Every 2 cycles (approximately 56 days) Response was evaluated by the RECIST. Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive disease (PD)is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center, 9000 Rockville Pike
🇺🇸Bethesda, Maryland, United States
National Institutes of Health Clinical Center, 9000 Rockville Pike🇺🇸Bethesda, Maryland, United States