A Phase II Study of AZD2171 in Metastatic Androgen Independent Prostate Cancer
- AZD2171 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
- No known effective therapy in patients with progressive androgen-independent prostate
cancer after treatment with docetaxel.
- 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 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 ELISA, pharmacogenetic analysis of KDR variants and
single nucleotide polymorphisms, and pharmacokinetic characterization of AZD2171
- Metastatic progressive androgen-independent prostate cancer.
- Prior treatment with docetaxel.
- May not have QTc greater than 470 msec or greater than 1+ proteinuria on 2 consecutive
dipsticks no less than 1 week apart.
- 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 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
Masking: Open Label, Primary Purpose: Treatment
6-month progression-free survival.
William L Dahut, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|