Therapy With Docetaxel and ZD1839 for Patients Who Have Advanced Breast Cancer
|First Received Date ICMJE||January 24, 2003|
|Last Updated Date||December 13, 2007|
|Start Date ICMJE||January 2003|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00052169 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Therapy With Docetaxel and ZD1839 for Patients Who Have Advanced Breast Cancer|
|Official Title ICMJE||A Phase 2, Multi-Center Trial of ZD1839 (IRESSA) in Combination With Docetaxel as First-Line Treatment in Patients With Advanced Breast Cancer|
The purpose of this study is to learn how breast cancer tumors respond to treatment combining the drugs docetaxel and ZD1839.
Patients with advanced breast cancer continue to have an extremely poor prognosis with an average life expectancy of approximately 2 years. Novel treatments designed to exploit biologic properties of the tumor are urgently required as a means to improve the outcome for the large numbers of patients who relapse after receiving optimal chemotherapy treatments.
Overexpresssion of EGFR and/or TGF-alpha is frequent in human breast cancer and has been correlated in many cases with poor prognostic features. Inhibition of the EGFR pathway has been proposed as a potential therapeutic modality in advanced breast cancer. The antiproliferative activity of ZD 1839 in combination with cytotoxic drugs, such as docetaxel was evaluated in breast cancer cell lines ZR-75-1 and MCF-10A ras that coexpress EGFR and TGF-alpha. Combination treatment demonstrated dose dependent supra-additive growth inhibition and markedly enhanced apoptotic cell death.
Although taxanes bind to the microtubular network in cells that is essential for mitotic and interphase cellular functions, the mechanism by which these agents induce cell death is not entirely clear. Docetaxel has also shown dose-dependent anti-angiogenic activity. Thus, the mechanism(s) of anti-tumor activity of docetaxel remain unclear and combinations of signal transduction pathway inhibition and/or anti-angiogenesis may provide potentiation of concurrent ZD 1839 and docetaxel therapy.
This phase 2 trial is designed to prospectively investigate the efficacy and safetey of combination therapy with ZD 1839 and docetaxel in patients with metastatic breast cancer.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 2|
|Study Design ICMJE||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Condition ICMJE||Breast Neoplasms|
|Intervention ICMJE||Drug: ZD1839 in combination with docetaxel
Docetaxel given as 75 mg/m2 IV every 3 weeks combined with ZD1839 (IRESSA) 250 mg orally daily until disease progression or withdrawal criteria are met.
|Study Arm (s)||Not Provided|
|Publications *||Dennison SK, Jacobs SA, Wilson JW, Seeger J, Cescon TP, Raymond JM, Geyer CE, Wolmark N, Swain SM. A phase II clinical trial of ZD1839 (Iressatrade mark) in combination with docetaxel as first-line treatment in patients with advanced breast cancer. Invest New Drugs. 2007 Dec;25(6):545-51. Epub 2007 Jun 12.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||September 2006|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||18 Years and older|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT00052169|
|Other Study ID Numbers ICMJE||NSABP FB-IR-002|
|Has Data Monitoring Committee||No|
|Responsible Party||Norman Wolmark, MD/Chairman, NSABP Foundation Inc., NSABP Foundation, Inc.|
|Study Sponsor ICMJE||National Surgical Adjuvant Breast and Bowel Project (NSABP)|
|Information Provided By||National Surgical Adjuvant Breast and Bowel Project (NSABP)|
|Verification Date||December 2007|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP