RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Anastrozole may fight breast cancer by blocking the production of estrogen by the tumor cells. Biological therapies such as ZD 1839 may interfere with the growth of the tumor cells and slow the growth of advanced solid tumors. Combining anastrozole with ZD 1839 may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining anastrozole with ZD 1839 in treating postmenopausal women who have metastatic breast cancer that has not responded to hormone therapy.

Condition	Treatment or Intervention	Phase
recurrent breast cancer stage IIIB breast cancer stage IIIC breast cancer stage IV breast cancer	Drug: anastrozole  Drug: gefitinib  Procedure: aromatase inhibition  Procedure: endocrine therapy  Procedure: enzyme inhibitor therapy  Procedure: hormone therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase II

OBJECTIVES:

• Determine the antitumor activity of anastrozole and ZD 1839, as measured by objective response (partial or complete) or stable disease at 6 months, in post-menopausal women with estrogen receptor-positive, hormone refractory, metastatic breast cancer.
• Determine the progression-free and overall survival of patients treated with this regimen.
• Determine the safety of this regimen in these patients.
• Determine the pharmacokinetics of this regimen in these patients.
• Correlate molecular markers with clinical benefit in patients treated with this regimen.

OUTLINE: This is an open-label, multicenter study.

Patients are stratified according to prior objective response to endocrine therapy (yes vs no).

Patients receive oral anastrozole once daily alone for 2 weeks. Patients then receive oral anastrozole and oral ZD 1839 once daily for 28 days. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed at 1 month and then monthly thereafter.

PROJECTED ACCRUAL: A total of 36-78 patients (18-39 per stratum) will be accrued for this study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed breast cancer
• Metastatic or locally advanced unresectable disease
• At least 1 measurable target lesion that has not been irradiated
• New lesions in a previously irradiated field allowed as sites of measurable disease
• Progressive disease after more than 2 months of aromatase inhibitor therapy
• No known CNS disease or unevaluated CNS symptoms suggestive of brain metastases
• Hormone receptor status:
• Estrogen receptor or progesterone receptor positive

PATIENT CHARACTERISTICS: Age

• 18 and over

Sex

• Female

Menopausal status

• Post-menopausal by 1 of the following criteria:
• Age 50 and over and has not menstruated during the past year or has castrate follicle-stimulating hormone (FSH) levels (greater than 40 IU/L)
• Under age 50 and has castrate FSH levels
• Received prior bilateral oophorectomy and has castrate FSH levels

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• ALT or AST no greater than 2.5 times ULN (5 times ULN if liver metastases present)

Renal

• Creatinine no greater than 1.5 times ULN

Cardiovascular

• No history of congestive heart failure requiring therapy
• No ventricular arrhythmia requiring therapy
• No unstable angina pectoris
• No myocardial infarction within the past 6 months

Other

• Able to swallow oral medication
• No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
• No known malabsorption condition or other condition that would impair absorption of study drug
• No active infection
• No other concurrent medical condition that would preclude study
• No known severe hypersensitivity to ZD 1839 or any excipients

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy except in adjuvant setting
• No concurrent chemotherapy for breast cancer

Endocrine therapy

• See Disease Characteristics
• More than 30 days since other prior hormonal therapy (including hormone replacement therapy and megestrol)
• Concurrent steroids for other reasons besides skin toxicity allowed
• No other concurrent hormonal therapy (including megestrol) for breast cancer

Radiotherapy

• See Disease Characteristics

Surgery

• Recovered from prior oncologic or other major surgery
• No concurrent ophthalmic surgery

Other

• More than 30 days since prior anticancer therapy
• More than 30 days since prior non-approved or investigational drugs
• No prior epidermal growth factor receptor or HER2 blockers
• No concurrent phenytoin, carbamazepine, barbiturates, rifampicin, phenobarbital, Hypericum perforatum, or systemic retinoids
• No other concurrent investigational therapy for breast cancer
• Concurrent bisphosphonates for metastatic bone disease allowed

Texas
      Cancer Therapy and Research Center, San Antonio,  Texas,  78229,  United States; Recruiting

Study chairs or principal investigators

Eric Keith Rowinsky, MD,  Study Chair,  Cancer Therapy and Research Center   

Study ID Numbers:  CDR0000257752; CTRC-IDD-0219; CTRC-IDD-1839US; CTRC-IDD-0228
Record last reviewed:  November 2002
Record first received:  November 12, 2002
ClinicalTrials.gov Identifier:  NCT00049062
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-05