Anastrozole With or Without Gefitinib in Treating Postmenopausal Women With Metastatic or Locally Recurrent Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using anastrozole may fight breast cancer by reducing the production of estrogen. Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Combining anastrozole with gefitinib may kill more tumor cells. PURPOSE: Randomized phase II trial to compare the effectiveness of anastrozole with or without gefitinib in treating postmenopausal women who have metastatic or locally recurrent breast cancer.

Detailed Description
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OBJECTIVES: Compare the 1 year antitumor activity of anastrozole with vs without gefitinib, in terms of progression-free survival, in postmenopausal women with metastatic or locally recurrent advanced breast cancer. Compare the objective tumor response and duration of tumor response in patients treated with these regimens. Compare the progression-free survival of patients treated with these regimens. Compare the safety of these regimens in these patients. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to participating center, dominant site of metastatic disease (bone alone vs other), prior chemotherapy (no vs yes), stage (metastatic vs locally recurrent), and measurability (measurable vs evaluable). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral anastrozole and oral gefitinib once daily. Arm II: Patients receive oral anastrozole and an oral placebo once daily. In both arms, treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 8 weeks until disease progression. PROJECTED ACCRUAL: A total of 108 patients (54 per treatment arm) will be accrued for this study.

Official Title
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An EORTC Randomized, Double Blind, Placebo-Controlled, Phase II Multi-Center Trial Of Anastrozole (Arimidex) In Combination With ZD 1839 (Iressa) Or Placebo In Patients With Advanced Breast Cancer

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 Radiologically or clinically evident metastatic or locally recurrent disease Locally advanced disease in elderly patients Bone metastases only allowed Failed prior tamoxifen therapy No rapidly progressive visceral metastases No uncontrolled CNS metastases Hormone receptor status: Estrogen receptor and/or progesterone receptor positive PATIENT CHARACTERISTICS: Age Postmenopausal Sex Female Menopausal status Postmenopausal, defined by any of the following: Natural menopause with last menses more than 1 year ago Radiotherapy-induced oophorectomy with last menses more than 1 year ago Chemotherapy-induced menopause with last menses more than 1 year ago AND serum follicle-stimulating hormone and luteinizing hormone and plasma estradiol levels clearly in the postmenopausal range Surgical castration Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic Not specified Hepatic Bilirubin no greater than 1.5 times upper limit of normal (ULN) Transaminases no greater than 2.5 times ULN No unstable or uncompensated hepatic disease Renal No unstable or uncompensated renal disease Cardiovascular No unstable or uncompensated cardiac disease Pulmonary No unstable or uncompensated pulmonary disease No clinically active interstitial lung disease Asymptomatic chronic stable radiographic changes are allowed Other No severe or uncontrolled systemic disease No other malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix, nonmelanoma skin cancer, or contralateral breast cancer No psychological, familial, sociological or geographical condition that would preclude study compliance and follow-up No grade 2 or greater unresolved chronic toxicity from prior anticancer therapy No unresolved ocular inflammation or infection No known hypersensitivity to anastrozole or gefitinib or any of their excipients PRIOR CONCURRENT THERAPY: Biologic therapy No prior trastuzumab (Herceptin) No concurrent biologic therapy Chemotherapy No more than 1 line of prior chemotherapy in the adjuvant or metastatic setting No concurrent chemotherapy Endocrine therapy At least 2 years since prior aromatase inhibitors (e.g., anastrozole, letrozole, or exemestane) in the adjuvant setting Prior tamoxifen or fulvestrant in the adjuvant and/or metastatic setting allowed No prior aromatase inhibitors for metastatic disease No other concurrent hormonal therapy Radiotherapy No concurrent radiotherapy to any metastatic site Surgery No surgery during and within 4 days after the last dose of gefitinib Other At least 30 days since prior investigational drugs No prior anti-epidermal growth factor therapy No prior anti-vascular endothelial growth factor therapy (i.e., tyrosine kinase inhibitor receptor) No concurrent administration of any of the following drugs: Phenytoin Carbamazepine Rifampin Phenobarbital Hypericum perforatum (St John's Wort) No other concurrent investigational drugs or treatment No other concurrent cancer treatment No concurrent systemic retinoids Concurrent bisphosphonate therapy for the treatment and prevention of bony metastases is allowed provided therapy was initiated prior to study entry Bisphosphonates may be initiated during study only for the treatment of hypercalcemia
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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arimidex + Iressa® 250 mg<br>Arimidex + Iressa® 250 mg Treatment should be administered until documented disease progression, unacceptable toxicity as judged by the responsible physician or patient refusal | Drug: anastrozole<br> <br> Drug: gefitinib<br> <br> |
| Active Comparator: Arimidex + Placebo<br>Treatment should be administered until documented disease progression, unacceptable toxicity as judged by the responsible physician or patient refusal | Drug: anastrozole<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival at 1 year |  | at 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response as measured by RECIST |  | from randomisation | 
| Duration of response as measured by RECIST |  | response duration | 
| Safety as measured by CTC v2.0 |  | from randomization | 

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