Therapy With Docetaxel and ZD1839 for Patients Who Have Advanced Breast Cancer - Full Text View

Sponsor:	National Surgical Adjuvant Breast and Bowel Project (NSABP)
Collaborator:	AstraZeneca
Information provided by:	National Surgical Adjuvant Breast and Bowel Project (NSABP)
ClinicalTrials.gov Identifier:	NCT00052169

Purpose

The purpose of this study is to learn how breast cancer tumors respond to treatment combining the drugs docetaxel and ZD1839.

Condition	Intervention	Phase
Breast Neoplasms	Drug: ZD1839 in combination with docetaxel	Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Phase 2, Multi-Center Trial of ZD1839 (IRESSA) in Combination With Docetaxel as First-Line Treatment in Patients With Advanced Breast Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Docetaxel ZD1839

U.S. FDA Resources

Further study details as provided by National Surgical Adjuvant Breast and Bowel Project (NSABP):

Primary Outcome Measures:

To estimate the clinical benefit rate of the combination of ZD 1839 and docetaxel; clinical benefit measured by clinical response, pathologic response, and stable disease (SD greater than or equal to 24 weeks) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
To characterize the safety profile of the combination of ZD 1839 and docetaxel as measured by the frequency and severity of adverse events. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To estimate the duration of clinical benefit. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
To estimate the objective tumor response rate (using RECIST best overall response of CR + PR). [ Time Frame: 2 years ] [ Designated as safety issue: No ]
To estimate the duration of tumor response. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
To estimate progression-free survival. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
To estimate time to treatment failure by measuring time to treatment failure (includes disease progression, second primary cancer, death from any cause, or discontinuation of protocol therapy in the absence of disease progression). [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment:	33
Study Start Date:	January 2003
Study Completion Date:	September 2006

Intervention Details:

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.

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria

Histologic confirmation of breast cancer
Signed consent
Current diagnosis of metastatic breast cancer
At least one uni-dimensionally measurable lesion with clearly defined margins
Patients taking bisphosphonates for documented prior bone metastasis may be included
Patients may have received prior adjuvant chemotherapy including an anthracycline and/or an alkylating agent. Patients may have received prior paclitaxel or trastuzumab for adjuvant therapy. Patients may not have received prior docetaxel treatment
Patients may have received unlimited prior hormonal therapy regimens for metastatic disease or adjuvant therapy and must have documentation of progressive disease prior to entry. Hormonal therapy must be discontinued at least 2 weeks prior to study entry
Patients may have received prior radiation therapy provided it was completed at least 2 weeks before study entry. Prior radiotherapy to treat bone metastasis or spinal cord compression is permitted provided it was completed prior to study entry
Zubrod performance status 0, 1, or 2
Life expectancy of 12 weeks or more in opinion of investigator
LVEF greater than or equal to LLN without clinical signs or symptoms of heart failure
adequate bone marrow, hepatic, and renal function

Ineligibility Criteria

Prior ZD1839 or other anti EGFR or small molecule TKI
Previous or concurrent chemo or Herceptin for metastatic breast cancer
Unresolved non-permanent major end organ chronic toxicity from previous anticancer therapy greater than CTC grade 2
Radiation therapy less than 14 days before study entry, with exception of RT to treat bone metastasis or spinal cord compression
Incomplete healing of surgical incision from previous major surgery
Newly diagnosed (within 12 weeks) intracerebral metastases
Signs of neurological symptoms consistent with new onset spinal cord compression
Evidence of severe or uncontrolled systemic disease
Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for patient to participate
Pregnancy or breast feeding
Patients who are currently using contact lenses. Patients who discontinue wearing contact lenses prior to study entry are eligible.
Patients with untreated ocular inflammation or infection
Patients with contraindications to corticosteroid use
History of another malignancy within past 5 years that could confound diagnosis or staging of breast cancer
Patients receiving other investigational drugs
Previous docetaxel treatment
Patients currently taking systemic retinoids or herbal medicines
Patients currently taking drugs known to induce Cyt P4503A4

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00052169

Locations

United States, Pennsylvania
NSABP Operations Center
Pittsburgh, Pennsylvania, United States, 15212

Sponsors and Collaborators

National Surgical Adjuvant Breast and Bowel Project (NSABP)

AstraZeneca

Investigators

Principal Investigator:

Norman Wolmark, MD

NSABP Foundation, Inc.

More Information

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.

Responsible Party:	NSABP Foundation, Inc. ( Norman Wolmark, MD/Chairman, NSABP Foundation Inc. )
Study ID Numbers:	NSABP FB-IR-002
Study First Received:	January 24, 2003
Last Updated:	December 13, 2007
ClinicalTrials.gov Identifier:	NCT00052169 History of Changes
Health Authority:	United States: Food and Drug Administration; United States: Institutional Review Board

Keywords provided by National Surgical Adjuvant Breast and Bowel Project (NSABP):

metastatic breast cancer
docetaxel
Taxotere
ZD 1839

gefitinib
NSABP
advanced breast cancer
AstraZeneca

Additional relevant MeSH terms:

Skin Diseases
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Breast Neoplasms
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions

Docetaxel
Neoplasms
Neoplasms by Site
Therapeutic Uses
Gefitinib
Breast Diseases

ClinicalTrials.gov processed this record on November 27, 2009