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A Phase 2, Multi-Center Trial of ZD1839 (IRESSA) in Combination With Docetaxel as First-Line Treatment in Patients With Advanced Breast Cancer

Phase 2
18 Years
Not Enrolling
Breast Neoplasms

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Trial Information

A Phase 2, Multi-Center Trial of ZD1839 (IRESSA) in Combination With Docetaxel as First-Line Treatment in Patients With Advanced Breast Cancer

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.

Inclusion 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

- 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

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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)

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Norman Wolmark, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

NSABP Foundation, Inc.


United States: Food and Drug Administration

Study ID:




Start Date:

January 2003

Completion Date:

September 2006

Related Keywords:

  • Breast Neoplasms
  • metastatic breast cancer
  • docetaxel
  • Taxotere
  • ZD 1839
  • gefitinib
  • advanced breast cancer
  • AstraZeneca
  • Breast Neoplasms
  • Neoplasms



NSABP Operations Center Pittsburgh, Pennsylvania  15212