AZD2171 and Combination Chemotherapy in Treating Women With Locally Advanced Breast Cancer
|ClinicalTrials.gov Identifier: NCT00310089|
Recruitment Status : Completed
First Posted : April 3, 2006
Last Update Posted : June 20, 2013
RATIONALE: AZD2171 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. Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving AZD2171 together with combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed and may kill more tumor cells.
PURPOSE: This randomized clinical trial is studying how well giving AZD2171 together with combination chemotherapy works in treating women with locally advanced breast cancer.
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer||Biological: filgrastim Biological: pegfilgrastim Drug: cediranib maleate Drug: cyclophosphamide Drug: docetaxel Drug: doxorubicin hydrochloride Other: laboratory biomarker analysis Procedure: conventional surgery Procedure: neoadjuvant therapy||Not Applicable|
- Determine the overall pathologic complete response rate in women with previously untreated, locally advanced breast cancer treated with neoadjuvant AZD2171, doxorubicin hydrochloride, cyclophosphamide, and docetaxel.
- Compare changes in pretreatment levels of pKDR after 1 course of AZD2171 vs no medication.
- Determine the number of patients who respond to combination therapy beginning with the second course of therapy.
- Determine the clinical response rate in patients treated with this regimen.
- Determine the safety of this regimen in these patients.
- Determine the changes in tumor proliferation (Ki67) in these patients.
- Determine the pharmacokinetics and pharmacogenetics of this regimen in these patients.
- Correlate angiogenic parameters with tumor response in these patients.
- Determine tumor vascularity and permeability before and after treatment as seen on dynamic contrast-enhanced MRI and initial area under the gadolinium curve.
- Determine tumor choline levels before and after treatment as measured by quantitative single-voxel MR spectroscopy and correlate with response.
OUTLINE: This is a multicenter, randomized, pilot study. Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral AZD2171 once daily on days 1-7* during course 1. During the second and subsequent courses, patients receive oral AZD2171 once daily on days 1-21, doxorubicin hydrochloride IV over 3-5 minutes, cyclophosphamide IV over 30 minutes, and docetaxel IV over 1 hour on day 1. Patients also receive filgrastim (G-CSF) subcutaneously (SC) on days 2-11 or pegfilgrastim SC on day 2. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
NOTE: *If biopsy cannot be scheduled prior to day 7 or 8 of course 1, AZD2171 alone can be continued for up to 14 days.
- Arm II (control): Beginning during the second course, patients receive AZD2171, doxorubicin hydrochloride, cyclophosphamide, docetaxel, and G-CSF or pegfilgrastim as in arm I.
All patients undergo tumor biopsiesat at baseline, before courses 2 and 4, and 3 weels after completion of study treatment. Tissue is examined for various biomarkers (phosphorylated-KDR, -MAPK, and -Akt, Ki67, VEGF, and p53) and for DNA ploidy analysis**.
NOTE: **Patients also undergo dynamic contrast-enhanced MRI and quantitative magnetic resonance spectroscopy 1 week before beginning therapy, 24 hours after starting therapy, prior to courses 2, 4, and 6, and 3 weeks after completion of study treatment.
After completion of AZD2171 and chemotherapy, patients undergo surgical resection.
After completion of study treatment, patients are followed for 4 weeks.
PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||33 participants|
|Official Title:||A Pilot Study to Evaluate The Effects of Neoadjuvant AZD2171, a VEGF Receptor Tyrosine Kinase Inhibitor With Docetaxel, Doxorubicin, and Cyclophosphamide Chemotherapy in Previously Untreated Locally Advanced Breast Cancer|
|Study Start Date :||January 2006|
|Actual Study Completion Date :||July 2007|
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00310089
|United States, Maryland|
|Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support|
|Bethesda, Maryland, United States, 20892-1182|
|United States, New Jersey|
|Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School|
|New Brunswick, New Jersey, United States, 08903|
|Study Chair:||Neelima Denduluri, MD||National Cancer Institute (NCI)|