Anastrozole and ZD 1839 in Treating Postmenopausal Women With Metastatic Breast Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase II And Biologic Correlative Study Investigating ARIMIDEX In Combination With IRESSA (ZD1839) In Post-Menopausal Patients With Estrogen Receptor-Positive Metastatic Breast Carcinoma Who Have Previously Failed Hormonal Therapy

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: anastrozole
* Drug: gefitinib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: anastrozole|nan|
|Drug: gefitinib|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer